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The study aimed to assess the impact of zinc oxide nanoparticles (ZnONPs) on rats' neurobehavior compared to bulk zinc oxide (BZnO). Thirty male Sprague-Dawley rats were randomly assigned to five groups. The control group received Tween 80 (10%), while the ZnONP groups were given ZnONPs at 5 and 10 mg/kg body weight dosages, and the bulk zinc oxide (BZnO) groups received BZnO at the same dosages. Behavioral observations, neurobehavioral examinations, and assessments of brain tissue oxidative markers, neurotransmitter levels, and histopathological changes were performed. The results indicated that ZnONP at a dosage of 5 mg/kg improved general behavior, locomotor activity, memory, and recognition and reduced fearfulness in rats. Conversely, the higher dosage of 10 mg/kg and the bulk form had adverse effects on general behavior, locomotor activity, and learning ability, with the bulk form demonstrating the most severe impact-znONP-5 treatment increased antioxidant enzyme levels and decreased inflammatory markers. BZnO-5 exhibited lower oxidative stress markers, although still higher than BZnO-10. Furthermore, ZnONP-5 and BZnO-5 increased neurotransmitter levels compared to higher dosages. ZnONP-5 upregulated the expression of brain-derived neurotrophic factor (BDNF) mRNA, while BZnO-5 showed increased BDNF mRNA expression and decreased expression of genes related to apoptosis and inflammation. In summary, ZnONPs at 5 mg/kg demonstrated positive effects on rat brain function and behavior, while higher dosages and the bulk form had detrimental effects. In conclusion, the studies emphasized the importance of further assessing various doses and forms of zinc oxide on brain health, highlighting the significance of dosage considerations when using nanomaterials., (© 2024. The Author(s).)

The harmful impact of waterborne copper (Cu) as a common abiotic stressor in aquatic environments has gained much more interest. The present study aimed to investigate the utilization of zinc oxide nanoparticles (ZnONPs) dietary supplementation to mitigate the chronic toxicity of Cu in African catfish (Clarias gariepinus). Two hundred and forty fish (92.94 ± 0.13 g) were assigned into six groups for 60 days. Control (C), ZnONPs20, and ZnONPs30 groups were fed on basal diets fortified with 0, 20, and 30 mg kg -1 ZnONPs without Cu exposure. Cu, Cu + ZnONPs20, and Cu + ZnONPs30 groups were exposed to Cu at a dose of 10 mg L -1 and fed on basal diets fortified with 0, 20, and 30 mg kg -1 ZnONPs, respectively. The results revealed that the Cu-exposed fish experienced abnormal clinical signs and behavioral changes. The growth indices and acetylcholine esterase activity were significantly decreased (P < 0.05) in the Cu group. Meanwhile, hepatorenal and serum stress indices (P < 0.05) were significantly elevated with chronic Cu exposure. In addition, a higher expression of stress (P < 0.05) (heat shock protein 60 and hypoxia-inducible factor-1 alpha) and apoptotic-related genes (C/EBP homologous protein, caspase-3, and Bcl-2 Associated X-protein) with down-regulation (P < 0.05) of the anti-apoptotic-related genes (B-cell lymphoma 2 and proliferating cell nuclear antigen) was noticed in the Cu-exposed fish. Histopathological alterations in the gills, liver, kidney, and spleen were markedly reported in the Cu-exposed group. The dietary supplementation with ZnONPs significantly alleviated the negative impacts of chronic waterborne-Cu exposure on growth performance, physiological changes, gene expression, and tissue architecture, especially at 30 mg kg -1 diet level. In particular, the inclusion of ZnONPs at the 30 mg kg -1 diet level produced better outcomes than the 20 mg kg -1 diet. Overall, ZnONPs could be added as a feed supplement in the C. gariepinus diet to boost the fish's health and productivity and alleviate the stress condition brought on by Cu exposure., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Due to their distinctive properties, several eco-friendly metal oxide nanoparticles were assessed for their possible cardioprotective properties. Acrylamide (ACD), a pervasive chemical in food and the environment, has been linked to cardiac toxicity. Therefore, this study examined the probable protective effect of green synthesized zinc oxide nanoparticles (GS-ZNPs) against ACD-oral exposure-induced cardiac damage in rats. For 60 days, 40 male Sprague-Dawley rats were separated into four sets that orally administered distilled water, 10-mg GS-ZNP/kg b.w., 20-mg ACD/kg b.w., or GS-ZNP + ACD. Then, cardiac damage indicators comprising CPK, CK-MB, cTn, and LDH were assessed. Besides, cardiac tissues' architecture, oxidative stress indicators, and Zn content were evaluated. The mRNA expression of the ERS-related genes, including ATF3, ATF4, ATF6, XBP-1, CHOP, JNKs, and BiP, were determined. Moreover, ERS-dependent anti-apoptotic (BCL-2) and apoptotic (Caspase-3 and BAX) genes mRNA expression were analyzed. The results showed that GS-ZNP significantly alleviated the increased ACD-induced serum cardiac damage indicators, MDA tissue content, and histopathological changes. Furthermore, the ACD-induced reduction of antioxidants and Zn heart contents were significantly reestablished by GS-ZNP. Furthermore, the ACD-induced upregulation of the ERS-encoding genes and apoptotic genes was reversed by GS-ZNP. Besides, the ACD-induced BCL-2 downregulation was counteracted by GS-ZNP. Overall, GS-ZNP could be a biologically potent compound to alleviate ACD's cardiotoxic effects, possibly by controlling the ERS and apoptosis-related genes and antioxidant activity., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Depression, a devastating brain illness, necessitates the exploration of novel antidepressant treatments. We evaluated the antidepressant effects of free curcumin, zinc oxide nanoparticles (ZnO NPs), and curcumin-conjugated zinc oxide nanoparticles (Zn(cur)O NPs). The nanoformulations were extensively characterized using advanced techniques. An acute toxicity study ensured the safety of Zn(cur)O NPs. Rats were assigned to one of five groups: control, reserpine-induced depression model, treatment with ZnO NPs, free curcumin, or Zn(cur)O NPs. Behavioral assessments (forced swimming test [FST] and open-field test [OFT]) and neurochemical analyses were conducted. Zn(cur)O NPs exhibited superior efficacy in ameliorating reserpine-induced behavioral and neurochemical effects compared to free curcumin and ZnO NPs. The reserpine-induced model displayed reduced motor activity, swimming time, and increased immobility time in the FST and OFT. Treatment with Zn(cur)O NPs 45 mg/kg significantly improved motor activity and reduced immobility time. Furthermore, Zn(cur)O NPs decreased malondialdehyde (MDA) levels while increasing reduced glutathione (GSH) and catalase (CAT) levels. Additionally, concentrations of serotonin (5-HT) and norepinephrine (NE) increased. In conclusion, curcumin-conjugated zinc oxide nanoparticles demonstrate potent antidepressant effects, alleviating depressive-like behavior in rats. These findings support Zn(cur)O NPs as a promising therapeutic strategy for depression management, warranting further investigation and clinical validation., (© 2023. The Author(s).)

Cancer chemotherapy is still a serious challenge. Chemo-resistance and destructive side effects of chemotherapy drugs are the most critical limitations of chemotherapy. Chemo-resistance is the leading cause of chemotherapy failure. Chemo-resistance, which refers to the resistance of cancer cells to the anticancer effects of chemotherapy drugs, is caused by various reasons. Among the most important of these reasons is the increase in the efflux of chemotherapy drugs due to the rise in the expression and activity of ABC transporters, the weakening of apoptosis, and the strengthening of stemness. In the last decade, a significant number of studies focused on the application of nanotechnology in cancer treatment. Considering the anti-cancer properties of zinc, zinc oxide nanoparticles have received much attention in recent years. Some studies have indicated that zinc oxide nanoparticles can target the critical mechanisms of cancer chemo-resistance and enhance the effectiveness of chemotherapy drugs. These studies have shown that zinc oxide nanoparticles can reduce the activity of ABC transporters, increase DNA damage and apoptosis, and attenuate stemness in cancer cells, leading to enhanced chemo-sensitivity. Some other studies have also shown that zinc oxide nanoparticles in low doses can be helpful in minimizing the harmful side effects of chemotherapy drugs. In this article, after a brief overview of the mechanisms of chemo-resistance and anticancer effects of zinc, we will review all these studies in detail., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

A feeding trial of 5-week duration was performed to assess the response of broiler chicks to dietary supplementation with different doses of myco-fabricated zinc oxide nanoparticles (ZONPs) on blood indices, physiological, immunological response, antioxidant status, intestinal microbial count, and histological changes in immune organs. A total of 162 3-day-old Ross 308 broiler chicks were weighed individually and distributed equally into 3 dietary treatments with 6 replicate of 9 chicks in each in a completely randomized design. Chicks were fed ad libitum a basal ration prepared as starter, grower, and finisher supplemented with 0 (T1, control), 40 (T2), and 60 (T3) mg zinc oxide nanoparticles (ZONPs)/kg feed. Results showed that supplementing with ZONPs at both studied levels increased the relative weights of the spleen, bursa, thymus, and liver and decreased the relative weight of the kidney, gizzard, and intestine. A significant increase in the concentrations of hemoglobin (Hb), hematocrit (PCV%), red and white blood cell counts, total protein (TP), globulin (GLOB), aspartate transferase (AST), alanine transferase (ALT), alkaline phosphatase (ALP), superoxide dismutase (SOD), glutathione peroxidase (GPx), and total antioxidant capacity (TAC) and a significant decrease in malonaldehyde (MDA), uric acid, and creatinine concentration were observed. Furthermore, all immunological organs showed histological alteration and increased both types of immunity in ZONPs groups with more pronounced effects in the T2 group., (© 2023. The Author(s).)

Zinc oxide nanoparticles (nano-ZnO) have diverse applications in numerous biomedical processes. The present study explored the effects of these nanoparticles on antioxidation, inflammation, tight junction integrity, and apoptosis in heat-stressed bovine intestinal epithelial cells (BIECs). Primary BIECs that were isolated and cultured from calves either were subjected to heat stress alone (42°C for 6 h) or were simultaneously heat-stressed and treated with nano-ZnO (0.8 μg/mL). Cell viability, apoptosis, and expression of genes involved in antioxidation (Nrf2, HO-1, SOD1, and GCLM), inflammation-related genes (TLR4, NF-κB, TNF-α, IL-6, IL-8, and IL-10), intestinal barrier genes (Claudin, Occludin, and ZO-1), and apoptosis-related genes (Cyt-c, Caspase-3, and Caspase-9) were assessed to evaluate the effect of nano-ZnO on heat-stressed BIECs. The nanoparticles significantly increased cell viability and decreased the rate of apoptosis of BIECs induced by heat stress. In addition, nano-ZnO promoted the expression of antioxidant-related genes HO-1 and GCLM and anti-inflammatory cytokine gene IL-10, and inhibited the pro-inflammatory cytokine-related genes IL-6 and IL-8. The nanoparticles also enhanced expression of the Claudin and ZO-1 genes, and decreased expression of the apoptosis-related genes Cyt-c and Caspase-3. These results reveal that nano-ZnO improve the antioxidant and immune capacity of BIECs and mitigate apoptosis of intestinal epithelial cells induced by heat stress. Thus, nano-ZnO have potential for detrimental the adverse effects of heat stress in dairy cows., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The zinc oxide nanoparticles (ZnONPs) have attracted exhilarating research interest due to their novel distinguishing characteristics such as size, shape, high surface activity, large surface area and biocompatibility. Being highly bioavailable and exerting a superior efficacy than conventional zinc sources, ZnONPs is emerging as an alternative feed supplement for poultry. The present study involves the synthesis of ZnONPs through a cost effective and eco-friendly method using planetary ball milling technique and characterized for its size, shape, optical property, functional group and elemental concentration using particle size analyzer, Transmission Electron Microscopy, X-Ray Diffraction analysis, Fourier Transform Infra-Red spectroscopy, UV-Vis spectroscopy and Inductively Coupled Plasma-Mass Spectroscopy. In vitro cytotoxicity study using Baby Hamster kidney (BHK-21) cells, Vero cells and primary chick liver culture cells revealed that ZnONPs can be safely incorporated in the broiler chick's feed up to the concentration of 100 mg/kg. To investigate the effects of ZnONPs on production performances in broiler chicks, a feeding trial was carried out using 150-day-old broiler chicks randomly allotted in five treatment groups. The dietary treatment groups were: T 1 (80 mg/kg of zinc oxide), T 2 (60 mg/kg of zinc methionine) and T 3 , T 4 and T 5 received 60, 40 and 20 mg/kg of ZnONPs respectively. The results showed a significant improvement (p < 0.05) in the body weight gain and feed conversion ratio of broiler chicks supplemented with 20 and 40 mg/kg of ZnONPs. The ZnONPs supplementation significantly (p < 0.05) increased the dressing percentage in addition to significant (p < 0.05) reduction in the meat pH compared to inorganic and organic zinc supplementation. Overall, an eco-friendly method for ZnONPs synthesis was demonstrated and the optimum dietary level (20 mg/kg) of ZnONPs could enhance the growth, the meat quality and Zn uptake without any negative effects on selected serum biochemical parameters in the broiler chicks., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Recently, nano feed supplement research has great attention to improving healthy aquatic production and improving the aquatic environment. With the aims of the present study, chemical and green synthesized nanoparticles are characterized by various instrumentation analyses, namely UV-Vis spectrophotometry (UV-Vis), X-ray diffraction (XRD), Fourier transform infra-red (FTIR) spectroscopy, and scanning electron microscope (SEM). After characterization analysis of these nanoparticles utilized in aquatic animals, the composition ratio is as follows: controls (without ZnO-NPs (0 mg/L)), T1 (0.9 mg/L ZnO-NPs), T2 (1.9 mg/L ZnO-NPs), T3 (0.9 mg/L GZnO-NPs), T4 (1.9 mg/L GZnO-NPs). SEM investigation report demonstrates that the structure of the surface of green synthesized zinc oxide nanoparticles (GZnO-NPs) was conical shape and the size ranging was from 60 to 70 nm. Concerning hematological parameters, the quantity of hemoglobin increased in different doses of green zinc nanoparticles, but the values of MCV and MCH decreased somewhat. However, this decrease was the highest in the T2 group. Total protein and albumin decreased in T2 and triglyceride, cholesterol, glucose, cortisol, creatinine, and urea increased, while in T3 and T4 groups, changes in biochemical parameters were evaluated as positive. Mucosal and serum immunological parameters in the T2 group showed a significant decrease compared to other groups. In zinc nanoparticles, with increasing dose, oxidative damage is aggravated, so in the T2 group, a decrease in antioxidant enzymes and an increase in MDA were seen compared to other groups. In this regard, the concentration of liver enzymes AST and ALT increased in the T2 group compared with control and other groups. This can confirm liver damage in this dose compared with control and other groups. This research work suggests that green synthesized form of zinc nanoparticles in higher doses have less toxic effects in comparison to the chemical form of zinc nanoparticles and can act as suitable nutrient supplements in aquatic animals., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Multiple myeloma (MM) is a malignant clonal proliferative plasma cell tumor. Zinc oxide nanoparticles (ZnO NPs) are used for antibacterial and antitumor applications in the biomedical field. This study investigated the autophagy-induced effects of ZnO NPs on the MM cell line RPMI8226 and the underlying mechanism. After RPMI8226 cells were exposed to various concentrations of ZnO NPs, the cell survival rate, morphological changes, lactate dehydrogenase (LDH) levels, cell cycle arrest, and autophagic vacuoles were monitored. Moreover, we investigated the expression of Beclin 1 (Becn1), autophagy-related gene 5 (Atg5), and Atg12 at the mRNA and protein levels, as well as the level of light chain 3 (LC3). The results showed that ZnO NPs could effectively inhibit the proliferation and promote the death of RPMI8226 cells in vitro in a dose- and time-dependent manner. ZnO NPs increased LDH levels, enhanced monodansylcadaverine (MDC) fluorescence intensity, and induced cell cycle arrest at the G2/M phases in RPMI8226 cells. Moreover, ZnO NPs significantly increased the expression of Becn1, Atg5, and Atg12 at the mRNA and protein levels and stimulated the production of LC3. We further validated the results using the autophagy inhibitor 3-methyladenine (3‑MA). Overall, we observed that ZnO NPs can trigger autophagy signaling in RPMI8226 cells, which may be a potential therapeutic approach for MM., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Inflammatory bowel diseases (IBDs), including Crohn's disease and ulcerative colitis, are chronic relapsing inflammatory gastrointestinal tract diseases of uncertain origin, which are frequently associated with zinc deficiency. Animal models have a considerable value in elucidating the process of IBD. In this study, 50 male C57BL/6 J mice were randomly assigned to five groups: control group (Con), 2,4,6-trinitrobenzenesulfonic acid (TNBS) group, and three zinc supplementation groups, namely 160 ppm group, 400 ppm group, and 1000 ppm group. The results showed that supplementation of dietary zinc with zinc oxide could effectively relieve the severity of ulcerative colitis induced by TNBS in mice. We demonstrate that the protective mechanism involves the immunomodulation of dietary zinc by increasing CD3 + , CD3 + CD8 + , and Th2 cells, suppressing Th1 and Th17 cells, and decreasing the production of serum IL-1β and IL-18. The dietary zinc oxide seems to be able to suppress the NF-κB/NLRP3 signaling pathway by downregulating the mRNA and protein expression of NIK, IKK, NF-κB, and NLRP3. The results suggest that dietary supplementation of zinc oxide may protect against colitis, and proper daily zinc supplementation may reduce the risk of IBD., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The present study was undertaken for the production of encapsulated zinc and its evaluation in broiler chicken diet. The process of microencapsulation involved the use of polymers, gum arabic and maltodextrin with a maximum encapsulation of efficiency of 66%. Encapsulated material contained about 20% zinc oxide (ZnO) as core material following the freeze-drying process. One hundred and ninety-two-day-old broiler chicks were distributed in four groups in six replications having eight birds in each. The four groups comprised control (inorganic source of zinc), En-Zn-100 (encapsulated zinc at 100% of control), En-Zn-50 (encapsulated zinc at 50% of control), and Org-Zn-50 (Zn-methionine at 50% of control). The experiment was carried out for 35 days following standard management practices. The live weight gain, feed intake and FCR were comparable among groups. Plasma and muscle zinc (ppm) content was unaffected by the level or source of zinc supplementation. The zinc apparent ileal digestibility coefficient was significantly (P < 0.05) higher in En-Zn-50 fed groups, while crude protein digestibility was not affected by the level or form of Zn supplementation. Bone weight, length, and zinc content were comparable, and bone ash content was significantly different among the groups. Relative expression of ZnT2 was significantly upregulated in encapsulated zinc-fed groups. From the study, it could be concluded that supplementation of zinc either as encapsulated or organic form at 50% of inorganic source (ZnO) could be sufficient to maintain the growth performance, serum, tissue and bone mineral content in broiler chicken., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The present study was planned to evaluate the effect of dietary zinc-oxide (ZnO) nanoparticles synthesized by different plant extracts on egg production, egg quality, bone mineralization, and antioxidant capacity in caged layers. Nanoparticles of ZnO were synthesized by using extracts of Allium sativum (AS), Aloe vera (AV), Curcuma longa (CL), and Zingiber officinale (ZO). Different sources of nano ZnO (AS, AV, CL, and ZO) with varying levels (35, 70, or 105 ppm) were tested on 288 caged LSL layers of 25 weeks of age. Each diet was offered to 4 replicates of 6 birds each level and the duration of trial was 8 weeks. Daily egg production, feed consumption, and fortnightly egg quality parameters were recorded. Egg quality parameters (egg weight, egg mass, shape index, yolk index, albumen index, Haugh unit score, specific gravity, and eggshell thickness) were determined fortnightly by taking 2 eggs from each replicate randomly. Antioxidant capacity and bone mineralization were determined at the end of the trial. Results showed that the nano ZnO preparations were not effective (P < 0.05) on laying performance but additional levels (70 ppm) improved egg production, feed conversion ratio, egg mass, Haugh unit score, and antioxidant capacity of chickens. An interaction was found among nanoparticles prepared by Allium sativum and Zingiber officianale extracts with 70 ppm level regarding total antioxidant capacity and egg production (P > 0.05). Interaction among source and level was not found regarding feed intake, feed conversion ratio, egg quality, bone characteristics, and concentration of Zn. Results of the present study suggest that nano ZnO sources may not be a factor that affects performance, but level affects the birds' physiology. Thus, it is concluded that nano ZnO with 70 ppm concentration is sufficient to optimize the laying performance., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Atrazine, as an herbicide, is used widely worldwide. Because of its prolonged persistence in the environment and accumulation in the body, atrazine exposure is a potential threat to human health. The present study evaluated the possible protective effects of zinc oxide nanoparticles and vitamin C against atrazine-induced hepatotoxicity in rats. Atrazine administered to rats orally at a dose of 300 mg/kg for 21 days caused liver oxidative stress as it increased malondialdehyde (MDA) formation and decreased reduced glutathione (GSH) contents. Atrazine induced inflammation accompanied by apoptosis via upregulation of hepatic gene expression levels of NF-κB, TNF-α, BAX, and caspase-3 and downregulation of Bcl-2 gene expression levels. Additionally, it disturbed the metabolic activities of cytochrome P450 as it downregulated hepatic gene expression levels of CYP1A1, CYP1B1, CYP2E1. The liver function biomarkers were greatly affected upon atrazine administration, and the serum levels of AST and ALT were significantly increased, while BWG%, albumin, globulins, and total proteins levels were markedly decreased. As a result of the above-mentioned influences of atrazine, histopathological changes in liver tissue were recorded in our findings. The administration of zinc oxide nanoparticles or vitamin C orally at a dose of 10 mg/kg and 200 mg/kg, respectively, for 30 days prior and along with atrazine, could significantly ameliorate the oxidative stress, inflammation, and apoptosis induced by atrazine and regulated the hepatic cytochrome P450 activities. Furthermore, they improved liver function biomarkers and histopathology. In conclusion, our results revealed that zinc oxide nanoparticles and vitamin C supplementations could effectively protect against atrazine-induced hepatotoxicity., (© 2023. The Author(s).)

Different nanoparticles (NPs) are currently being investigated for their potential role as cryoprotectant during semen cryopreservation in several mammalian species. It may be possible to improve semen quality following cryopreservation by supplementation of NPs in the freezing extenders. The present study was carried out in semen collected from four (4) Assam Hill Goat bucks (10 ejaculates per buck) to investigate the effect of supplementing zinc oxide (ZnO) and selenium (Se) NPs in Tris-citric acid-fructose yolk (TCFY) extender on in vitro sperm quality and in vivo fertility rate after freeze-thawing. The size morphology and zeta potential of ZnO and Se NPs were evaluated prior to its incorporation in the freezing extender. Qualified semen samples (> 70% progressive motility) were divided into five (5) aliquots and then diluted in TCFY extender containing ZnO and Se NP supplementation at different concentrations (T 0 , control; T 1 , 0.1 mg/mL ZnO NPs; T 2 , 0.5 mg/mL ZnO NPs; T 3 , 0.5 µg/mL Se NPs; and T 4 , 1 µg/mL Se NPs). Diluted semen was packed in 0.25 mL straws and then stored in liquid nitrogen. After thawing, post-thaw in vitro sperm attributes were evaluated. Finally, the effect of NPs on in vivo fertility rate was checked in heat-synched does (n = 70) by artificial insemination (AI) using straws that showed superior results during the in vitro study. Results showed that ZnO and Se NPs were poly-crystalline in nature with particle size below 100 nm (nm). The evaluated post-thaw sperm in vitro attributes were significantly (p < 0.001) higher in T 1 in comparison to T 0 . The antioxidant enzyme activities were significantly (p < 0.001) higher in T 1 . Lipid peroxidation (LPO) profile was significantly (p < 0.001) lower in T 1 . Sperm motility and mitochondrial membrane potential (MMP) had a highly significant (r = 0.580, p < 0.05) association in T 1 . No significant (p > 0.05) differences in pregnancy rates were recorded after AI in the different treatments. In conclusion, extender supplemented with 0.1 mg/mL ZnO NPs improved post-thaw semen quality of goat spermatozoa consequently by increasing activities of endogenous antioxidant enzymes thereby lowering LPO levels. However, improved in vitro outcomes might not correspond to improved field fertility outcomes., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

This study investigated the effect of novel zinc oxide nanoparticles (ZnO NPs) biosynthesized employing Papaver somniferum leaf on oxidative stress, necrosis, and apoptosis in the leukemia cancer THP-1 cell. The obtained ZnO was examined using SEM, AFM, and TEM microscopy, which revealed an irregular spherical morphology with a size ranging from 20 to 30 nm, and the UV-vis absorbance revealed a strong absorption peak in the range of 360-370, nm confirming the production of ZnO NPs. THP-1 cells were subjected to an MTT, an EdU proliferation, a lactate dehydrogenase release tests, a reactive oxygen species (ROS) induction experiment, a DAPI staining detection assay, and a flow cytometric analysis for Annexin V to measure the effects of ZnO NPs on cancer cell growth inhibition, apoptosis, and necrosis. Our results show that ZnO NPs inhibit THP-1 line in a concentration-dependent pattern. It was observed that ZnO NPs triggered necrosis (cell death) and apoptosis in the cell line. ZnO NPs massively improved the formation of intracellular ROS, which is crucial in deactivating the development of leukemic cells. In conclusion, ZnO nanoparticles synthesized using Papaver somniferum extract have the ability to inhibit proliferation leukemic cancer cells, making them potential anticancer agents., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Recently some metal-based nanoparticles have gained serious attention from aquaculture and the fish feed industry as feed supplements. Oral supplementation of zinc oxide nanoparticles (ZnO-NPs) in fish feed, replacing Zn acetate (conventionally used zinc), is suggested as a cost-effective and efficient approach. Our study assessed the response of Nile tilapia, Oreochromis niloticus, fingerlings after its diet supplemented with chemically synthesized ZnO-NPs and zinc acetate under controlled conditions. ZnO-NPs were chemically synthesized and characterized. Tilapia fingerlings with an average body weight of 09.12 ± 1.23 g were randomly distributed into five groups. An 8-week trial was set with control and four experimental groups. Basal diet (D1) was used as control, whereas D2, D3 and D4 comprising 20, 40, and 60 mgkg -1 ZnO-NPs supplementation were experimental diets. Additionally, D5 was composed of a basal diet supplemented with 40 mgkg -1 of conventionally used zinc acetate. Significant improvement (P < 0.05) was found in nanoparticles and Zn acetate supplemented groups as compared to control, while the 40 mgkg -1 Zn-NPs supplemented diet (D3) showed best performance in terms of health parameters, oxidative status and disease resistance. Antioxidant profiling was based on catalase, superoxide dismutase, glutathione's transferase, and malondialdehyde; hematology included Hb, WBCs, RBCs, HCT MCV, MCH and MCHC; immunological parameters comprised IgM, lysozyme activity, phagocytic activity, respiratory burst activity, cholesterol, aspartate aminotransferase, alanine aminotransferase, glucose content, and total serum proteins. We report that the D3 (40 mgkg -1 ZnO-NPs supplementation) significantly (P < 0.05) improved health-related parameters as compared to the other groups. Moreover, D3 also showed significantly decreased mortality percentage when challenged by Staphylococcus aureus, while the Zn acetate supplemented diet group showed better results as compared to control. Overall results suggest the basal diet supplemented with 40 mgkg -1 ZnO-NP for enhanced health parameters, oxidative status, immune response, and disease resistance. Hence, 40mgkg -1 ZnO-NP can be recommended to formulate the practical diet of fish to boost health improvement, immunomodulation, and resistance to bacterial disease., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

A 35-day trial was set to explore the effects of different dietary zinc sources on growth, insulin-like growth factor I (IGF-I) mRNA expression, meat quality, immune response, antioxidant activity, and immunohistochemistry of nuclear factor kappa B (NF-κ7B) of broiler chickens. Ross 308 broiler chicks (n = 156) were randomly assigned into four experimental groups. The G1 received the basal control diet without zinc supplementation; the G2, G3, and G4 were supplemented with zinc oxide, zinc lysine, and nano zinc oxide, respectively, at a level of 40 mg Zn/kg diet. The data revealed that nano zinc oxide linearly improved the overall growth performance parameters. Nano zinc oxide linearly elevated (P < 0.001) mRNA expression of IGF-I followed by G3. The pH value of breast muscle in G4 shows a linearly decreasing value (P < 0.001). Also, the linearly highest expressible release volume percentage and lightness (L*) value with the lowest redness (a*) value (P < 0.05) were recorded in G4 and G3. A numerical increase in the total antibody titer was recorded on the 35 th day in the G3 and G4. A numerical elevation in the superoxide dismutase (SOD) and a numerical reduction in the serum malondialdehyde (MDA) were recorded in the G4. The section of the liver from G4 revealed significantly very low expression of NF-κB staining. It is concluded that nano zinc oxide is considered the more trending zinc source. It had no negative effects on the health status and can be used in broiler diet premix., (© 2022. The Author(s).)

This study aims to investigate the effects of nanoparticles of zinc oxide (Nano-ZnO) supplementation on productive performance, nutrient digestibility, mineral retention, and blood biochemistry of Californian male rabbits under hot climatic conditions. A total of 100 Californian male rabbits 90 days of age (BW: 1790 ± 13 g) were randomly assigned to one of five treatment diets: Nano-ZnO at 0, 25, 50, 75, or 100 mg/kg, respectively, for 90 days. The rabbits were raised in an open house system (average ambient temperature of 39 °C, relative humidity of 30-35%, and temperature-humidity index of 33.6-34.0). Each treatment had 20 rabbits, and each rabbit was considered as a replicate. During the entire study period, there were no significant differences (P > 0.05) in BW, BW gain, feed intake, or feed conversion ratio between the treatment groups. Nano-ZnO supplementation at 25, 50, 75, and 100 mg/kg enhanced the digestibility coefficient of crude protein (CP) and ether extract (EE) considerably (quadratically, P < 0.05) when compared to the control group. In addition, when Nano-ZnO was supplemented at 25, 50, 75, and 100 mg/kg, serum levels of creatinine, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) were considerably lower than the non-supplemented control group. Furthermore, when comparing the control and Nano-ZnO-fed rabbits, serum testosterone concentrations increased significantly (P < 0.05) in the treated groups. In addition, compared to the other groups, the 50 mg/kg Nano-ZnO group had the highest cecal Lactobacilli spp. count. These findings suggest that supplementing Californian male rabbits with 50 mg/kg dietary Nano-ZnO enhanced CP and EE digestibility, cecal Lactobacilli spp., as well as serum testosterone levels, and decreased serum ALT and AST levels under hot climatic conditions., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The experiment was conducted to investigate the effect of supplementary different levels of zinc-threonine (Zn-Thr) and zinc oxide (ZnO) on the Zn bioavailability, biological characteristics and performance of honey bees (Apis mellifera L.). The experiments were carried out with seven treatments in a completely randomized design with five replicates for each treatment. During the experiment, groups were fed a basal diet without extra zinc (10.4 mg Zn/kg diet), and it was used as the control diet and 3 levels of 20, 40, and 60 mg Zn/kg were added to the diet by ZnO and Zn-Thr sources. The results showed that different levels of organic Zn significantly increased Zn and Fe content in the carcass of caged bees compared to different levels of inorganic Zn and control groups. Also, honey bees fed with levels of 40 and 60 mg Zn/kg Zn-Thr supplementation significantly had lower Malondialdehyde (MDA) concentration and higher ash content, protein content, superoxide dismutase (SOD) activity in their tissues. In addition, they showed more life span, feed intake, population, brood rearing, and hive weight gain (p < 0.05). Totally, the results of the present experiments revealed that diets supplied with organic Zn compared to inorganic Zn play significant roles in the improvement of Zn bioavailability, biological characteristics, and performance in honey bees., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

An experiment was conducted to evaluate the effect of copper oxide (Cu 2 O) and potentiated zinc oxide (ZnO) on performance, intestinal morphology, oocyst excretion, coccidial lesion scores, and antioxidant properties in broilers during an Eimeria spp. challenge. A total of 288 1-day-old male broiler chickens (Ross 308) were divided into 18 treatments. Treatments included three levels of Cu (0, 15, or 150 mg/kg) from Cu 2 O and three levels of Zn (0, 80, or 160 mg/kg) from potentiated ZnO which were added to the basal diet and fed to broilers with or without challenge, using a completely randomized design in a factorial arrangement for 42 days. Live body weight, feed intake, mortality, and the cause of death were recorded weekly and histomorphology of jejunum was measured at the end of the experiment. Results showed that birds fed Cu and Zn linearly decreased (P < 0.0001) oocyst shedding. The number of excreted oocysts was reduced eight times in broilers fed a diet containing 150 mg/kg copper from Cu 2 O and 160 mg/kg zinc from potentiated ZnO, compared to the infected group without Cu and Zn supplementation (P < 0.0001). Microscopic features of both non-challenged and challenged broiler jejunum revealed significant improvement along with increased Cu 2 O and potentiated ZnO doses. Supplementation of Cu 2 O and potentiated ZnO decreased the jejunum structure damages and intestinal lesion score (P < 0.002). Eimeria caused a decrease (P < 0.006) in total antioxidant capacity. Superoxide dismutase increased by dietary zinc supplementation (P < 0.05). Results suggested that a combination of Cu 2 O and potentiated ZnO could exhibit efficient anticoccidial activity., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Zinc is an essential element affecting immune responses in aquatic organisms. In the present research, the immunomodulating effect of zinc oxide nanoparticles (ZnO NPs) was studied in Nile tilapia (Oreochromis niloticus). The minimum inhibitory concentration of zinc oxide nanoparticles (ZnO NPs) for Aeromonas hydrophila was estimated at 60 µg/mL. To evaluate the efficacy of ZnO NPs for improving disease resistance against A. hydrophila, three hundred fish were divided into 5 groups. Fish in the group T1 maintained on the control feed, T2 and T3 feed on ZnO at 60 and 30 µg/g, while T4 and T5 received ZnO NPs at 60 and 30 µg/g, respectively for 8 weeks. Immune responses were evaluated by determining the phagocytic activity, serum antibacterial activity, lysozymes, respiratory burst activity, and also gene expression of immunoglobin M-2, tumor necrosis factor-α, interleukin (IL)-1β, heat shock proteins, IL-10, insulin growth factor 1, transforming growth factor-β2, superoxide dismutase enzyme, and catalase enzyme genes. Results indicated that groups that received ZnO NPs have exaggerated immune response and upregulation in the most of expressed immune-related genes. After the feeding trial, all groups were experimentally infected with A. hydrophila, and the mortality rate was monitored. Among all the treated groups, a higher survival rate and disease resistance were observed for fish that received ZnO NPs at 30 and 60 µg/g. The inclusion of ZnO NPs in O. niloticus feed improves both fish immune response and disease resistance against A. hydrophila., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

This study aimed to investigate the effects of different levels of zinc oxide nanoparticles on broilers' performance, nutrient digestibility, carcass criteria, and blood biochemistry. A total of 120 1-day-old unsexed broiler chickens (Ross 308) were fed zinc oxide nanoparticles at different levels (0, 20, 40, or 60 mg/kg) in their diets. Each treatment included 6 replicate pens with 5 birds each. The experiment lasted 42 days. The brooding temperatures were 37.8 °C, 35.8 °C, and 29.9 °C during 1-10 days, 11-21 days, and 22-42 days of age, respectively. The results revealed that dietary supplementation of nanoparticles of zinc oxide at 20, 40, and 60 mg/kg diet significantly improved body weight, body weight gain, and feed conversion ratio showing linear effects (P < 0.05) compared to the birds fed the control diet under hot climatic conditions. Dietary addition of zinc oxide nanoparticles at 20, 40, and 60 mg/kg linearly increased (P < 0.05) the nutrient digestibility of crude protein, crude fiber, and ether extract compared to the control group. Birds fed the supplemented diets had improved liver and kidney function without any negative effects on zinc, inorganic phosphorus, triiodothyronine (T 3 ), and thyroxine (T 4 ) levels in serum compared to the control. Diets supplemented with zinc oxide nanoparticles linearly (P < 0.05) improved the dressing percent and reduced abdominal fat percent compared to the control group. In view of the above findings, it can be concluded that dietary supplementations of zinc oxide nanoparticles at 20, 40, and 60 mg/kg resulted in improved growth performance, nutrient digestibility, carcass criteria, and liver and kidney functions of broiler chickens under hot environmental conditions., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The aim of the current study was to determine protective effects of betaine on depressive-like behaviors in zinc oxide nanoparticles (ZnO NPs) exposed mice. Forty male mice randomly allocated into four experimental groups. Group 1 kept as control and groups 2-4 received oral administration of betaine (30 mg/kg), ZnO NPs (600 mg/kg), and ZnO NPs (600 mg/kg) 1 h after pre-administration of betaine (30 mg/kg) for 7 days, respectively. Then, forced swimming test (FST), tail suspension test (TST), open field test (OFT), and rotarod tests were done. Furthermore, serum malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GPx), and total antioxidant capacity (TAC) levels were determined. Hippocampal tissue samples were collected for histopathological assessment. According to the results, treatment with ZnO NPs significantly increased immobility time in the FST and TST (P<0.05). Betaine significantly decreased immobility time in the FST and TST (P<0.05). Pretreatment with betaine significantly decreased ZnO NPs-induced alterations in the FST and TST (P<0.05). The duration of staying on the rotarod and the numbers of crossings in the OFT significantly decreased in the mice that received ZnO NPs (P<0.05). These results were significantly improved in betaine+ZnO NPs treated mice as compared to the ZnO NPs group (P<0.05). Treatment with ZnO NPs significantly increased serum MDA level while decreased SOD and GPx compared to the control group (P<0.05). These changes were effectively ameliorated by pretreatment with betaine compared to the ZnO NPs group (P<0.05). No significant effect on serum TAC level was observed in all groups (P˃0.05). Administration of ZnO NPs decreased the thickness of hippocampus and pyramidal neurons in the hippocampal dentate gyrus (DG) and CA1 regions were sparsely arranged. Pretreatment with betaine caused an improvement in the histological features of the hippocampus when compared with ZnO NPs-treated mice. Taken together, these results suggest that betaine has protective role against ZnO NPs-induced toxicity in mice., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Zinc is an essential element for metabolism of Nile tilapia (Oreochromis niloticus). Nanomaterials have important benefits in aquaculture. The present study evaluated the effects of green-synthesized zinc oxide nanoparticles (ZnO-NPs) using Ulva fasciata extract as an anti-fungal agent against Candida albicans (C. albicans) in vitro and in vivo in O. niloticus. A total of 252 apparent healthy O. niloticus (20 ± 0.457 g/fish) were randomly allocated into six groups: The 1 st group fed on basal diet contaminated with C. albicans 15 × l0 6 CFU/g diet, the 2 nd group fed basal diet only, the 3 r d and 5 th groups fed the basal diet supplemented with 40 or 60 mg/kg ZnO-NPs, respectively, and the 4 th and 6 th groups fed the basal diet contaminated with C. albicans 15 × l0 6 CFU/g and concomitantly supplemented with 40 or 60 mg/kg ZnO-NPs, respectively. The experiment lasted for 8 weeks. The phyco-synthesized ZnO-NPs were characterized by XRD, UV-V, FTIR, TEM, and zeta potential. The anti-fungal activities of ZnO-NPs and the morphological changes to C. albicans cell due to ZnO-NPs were detected. The results revealed that dietary supplementation with the green-synthesized ZnO-NPs significantly improved the growth performance, survival, serum lysozyme activity, phagocytic activity, phagocytic index, respiratory burst activity, expression of immune-related genes (IL-1β, TGF, TNF-α), digestive enzyme activity, and histopathological finding in C. albicans-infected group, with a relative superiority to 40 mg/kg feed ZnO-NPs. It could be concluded that supplementing diets with 40 mg/kg of phyco-synthesized ZnO-NPs could be considered a better choice for controlling candidiasis in Nile tilapia., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The present study investigates the effect of different dietary protein levels suboptimum level (25%) and optimum level (35%), different Zn forms bulk zinc oxide (BZnO) or nanoparticles zinc oxide (NZnO), and their interaction on performance, intestinal topography, hematology, serum biochemical, antioxidant-immune responses, and related gene expression of Nile tilapia. Six experimental diets were formulated to contain approximately 25% and 35% crude protein and supplemented with Zn forms with 0 (normal level in ingredients), 60 mg kg -1 BZnO and 60 mg kg -1 nanoparticles of NZnO. Nile tilapia, Oreochromis niloticus, fingerlings (7.53 ± 0. 06 g) were fed on one of tested diets in triplicates with 5% of total biomass three times a day for 84 days. Results showed that, fish fed diet containing 35% crude protein and supplemented with NZnO form recorded the highest final body weight (FBW), weight gain (WG), and specific growth rate (SGR). However, no significant (P > 0.05) differences were recorded in FBW, WG, SGR, feed conversion ratio (FCR), and protein efficiency ratio (PER) between fish fed diet containing 35% crude protein without Zn supplementation and fish fed diet containing 25% crude protein supplemented with NZnO form. Either fish fed diet containing 25% or 35% crude protein and supplemented with NZnO exhibited the highest values of villi height/width. The highest absorption surface area (ASA) was obtained in fish fed diet containing 25% or 35% crude protein and supplemented with BZnO. Hemoglobin (Hb), hematocrit (Hct), and red blood cell count (RBCs) highest values were obtained for fish fed diet containing protein level 35% supplemented with NZnO. Fish fed diet containing protein level 35% and supplemented with NZnO had the lowest value of alanine amino transferase (ALT) and aspartate amino transferase (AST). The highest globulin value was recorded for fish provided with diet containing 35% crude protein and supplemented with BZnO followed by those fed diet containing 35% crude protein and supplemented with NZnO. Fish fed diet containing protein level 25% with NZnO supplementation recorded the highest super oxide dismutase (SOD), catalase (CAT), glutathione reductase (GSH), and glutathione peroxidase (GP X) , with decreasing malondialdehyde (MAD) values. The highest values of immunoglobulin g (IgG), immunoglobulin M (IgM), complement 4 (C4), and complement 3 (C3) were obtained for diet containing 35% crude protein and supplemented with NZnO form. Growth hormone gene (GH) was upregulated in fish fed 25% dietary protein without Zn supplementation, while it was downregulated in fish fed 25% dietary protein and supplemented with NZnO. Transcription of insulin-like growth factor-1 (IGF-I) gene recorded the highest value for fish fed 35% crude protein and supplemented with BZnO. This is although the diet of 35% crude protein + NZnO induced significant (IGF-I) gene expression compared with 25% crude protein with or without BZnO. Therefore, nano zinc is useful as a feed supplement for Nile tilapia (Oreochromis niloticus)., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Effective cancer therapy can be achieved by using nano-drug delivery systems which provide a targeted drug delivery strategy by overcoming the drawbacks of conventional treatments like chemotherapy and radiation. ZnO nanoparticles are a potent anticancer agent that causes tumor cell destruction with the targeted drug delivery. In this present study, green synthesis of ZnO nanoparticles has been done using the plant Solanum nigrum. The synthesized ZnO nanoparticles were studied by the characterization techniques like UV-visible spectroscopy, SEM, TEM, DLS, zeta potential, FTIR, and XRD. The synthesized ZnO nanoparticles of Solanum nigrum exhibited a significant anticancer activity against HeLa cell lines through the apoptotic pathway. The cytotoxicity of ZnO nanoparticles was assessed using MTT assay, wound healing assay, DAPI staining, and acridine orange and ethidium bromide double staining. The expression patterns of β-catenin, p53, caspase-3, and caspase-9 were analyzed using reverse transcriptase-PCR. The results obtained from the study indicate that the ZnO nanoparticles of Solanum nigrum possess a dose-dependent cytotoxic effect against HeLa cell lines through the inhibition of β-catenin and increasing the levels of p53, caspase-3, and caspase-9., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Zinc is one of the essential microelements involved in vital physiological and biological functions in the fish body. The study evaluated the growth performance, antioxidative capacity, and intestinal histomorphology of Grey Mullet (Liza ramada)-fed dietary zinc nanoparticles (ZnO-NPs) at 0, 10, 20, and 40 mg/kg for the first time. The final weight and specific growth rate (SGR) of Grey Mullet-fed dietary ZnO-NPs at 20 and 40 mg/kg were meaningfully enhanced (p < 0.05). Further, the weight gain (WG) was significantly higher in fish treated with ZnO-NPs than the control, and fish fed 20-40 mg/kg had the highest WG (p < 0.05). The feed conversion ratio (FCR) was meaningfully reduced in fish fed 20-40 mg ZnO-NPs/kg (p < 0.05). The histomorphology of the intestines revealed a significant improvement in villus height, villus width, and goblet cells by ZnO-NPs. The lysozyme activity, phagocytic activity, and phagocytic index showed higher levels in Grey Mullet-fed dietary ZnO-NPs at 20 mg/kg than fish fed 0, 10, and 40 mg/kg (p < 0.05). Superoxide dismutase (SOD) and catalase (CAT) were markedly improved in Grey Mullet treated with ZnO-NPs compared with the control, and the group of fish treated with 20 mg/kg had the highest SOD and CAT (p < 0.05). Glutathione peroxidase (GPx) was significantly higher in fish fed 20-40 mg/kg ZnO-NPs than fish fed 0-10 mg/kg and fish fed 40 mg ZnO-NPs/kg showing the highest GPx value (p < 0.05). The concentration of malondialdehyde was markedly lowered in Grey Mullet fed ZnO-NPs at varying levels (p < 0.05). Based on the overall results, the regression analysis suggests that ZnO-NPs can be included at 24.61-35.5 mg/kg for the best performances of Grey Mullet., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The current trial was conducted by using the 288 Japanese quails to evaluate the effects of a zinc-deficient diet supplemented with nano and micro zinc oxide on performance, fertility, hatchability, and egg quality characteristics. In this experiment, birds were randomly allocated to 9 dietary treatments includes diets supplemented with nano or micro particles of zinc oxide (amount of ZnO supplement for each treatment) to supply 49, 74, 99, and 124 mg zinc per kilogram of diet in a factorial arrangement (2 × 4) and a control non supplemented diet (24 mg/kg) with four replicates of eight birds (six females and two males) in each pen. Birds were fed the experimental diets from 47 to 75 days of age and had free access to water and feed during the experimental period. Results showed that Zn supplementation, regardless of particle size, improved the eggshell thickness (P < 0.01). A significant (P < 0.05) interaction was observed between zinc level and ZnO particle size for Shell breaking strength. Quails fed diets supplement with ZnO showed significantly higher egg weight and eggshell surface (P < 0.05) as compared with birds fed a non-supplemented control diet. Results obtained here showed that supplementation of nano ZnO enhanced fertility considerably. Application of non-linear quadratic models showed that the maximum egg production percentage was achieved when 67 or 72 mg/kg of dietary zinc was supplied from nano and micro ZnO, respectively. This result indicated that nano ZnO could reduce the zinc requirement in laying Japanese quail., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

This experiment was to study the effects of zinc oxide nanoparticles (ZnO-NPs) on growth, intestinal barrier, oxidative status, and mineral deposition. In total, 256 one-day-old chicks were randomly allotted to 4 dietary groups and fed with basal diet plus 80 mg/kg ZnSO 4 (ZnSO 4 group) or plus 40, 80, and 160 mg/kg ZnO-NPs, respectively, for 21 days. Compared with the ZnSO 4 group, dietary 40, 80, and 160 mg/kg ZnO-NPs did not alter growth (average daily gain, body weight, and gain to feed ratio), and serum activities of glutamic-pyruvic transaminase, alkaline phosphatase and glutamic oxalacetic transaminase (P > 0.05). However, dietary 80 and 160 mg/kg ZnO-NPs linearly decreased serum D-lactate content and diamine oxidase activity (P < 0.01). Moreover, 80 mg/kg ZnO-NPs enhanced zonula occludens-1 (ZO-1) mRNA expression in jejunal mucosa (P = 0.02). Dietary ZnO-NPs increased total antioxidant capacity activity (P = 0.01), and 80 mg/kg ZnO-NPs decreased malondialdehyde content in jejunal mucosa as compared to the ZnSO 4 group (P = 0.02). In contrast, dietary ZnO-NPs did not alter mRNA expressions of superoxide dismutase, catalase, glutathione peroxidase, glutathione S-transferase, heme oxygennase-1 (HO-1) and NAD (P)H: quinone oxidoreductase 1 (NQO1) (P > 0.05). No significant difference was found in selected mineral concentrations (Mn, Cu, Fe and Zn) in the liver among ZnSO 4 and 3 ZnO-NP groups (P > 0.05). However, 160 mg/kg ZnO-NPs increased fecal contents of Zn, Fe and Cu (P < 0.01), but did not affect fecal Mn level (P > 0.05). Therefore, results suggested that ZnO-NPs could be an additive to enhance the intestinal barrier and antioxidant capacity of broiler chicks, whereas the inclusion of 80 mg/kg would be more efficient., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

This study was aimed to investigate the synergistic effects of selenium (Se-NP) and zinc oxide (ZnO-NP) nanoparticles on growth performance, hemato-biochemical profile, immune and oxidative stress responses, and intestinal morphometry of Nile tilapia (Oreochromis niloticus). Monosex Nile tilapia (12.50 ± 1.03 g, N= 180) were randomly allocated into 4 groups in triplicates. Fish were fed diet supplemented with 0 Se-NP and Zn-NP (control group, CG), while fish in the other experimental groups were fed diet supplemented with 1 mg/kg diet Se-NP (Se-NP group), 10 mg/kg diet ZnO-NP (Zn-NP group), and a mixture of 1 and 10 mg/kg diet Se-NP and Zn-NP, respectively (Se/Zn-NP group) for 60 days. Fish fed diet containing Se-NP, Zn-NP, and Se/Zn-NP showed higher final body weight, weight gain, weight gain rate, specific growth rate, and lower feed conversion ratio with respect to CG (P<0.05) with the highest being in fish fed with Se/Zn-NP. Fish fed with Se/Zn-NP showed higher hemoglobin, red blood cells, and globulin (P<0.05). The highest phagocytic activity, phagocytic index, lysozyme activity, and immunoglobulin M was recorded in fish that received Se/Zn-NP followed by Se-NP, Zn-NP, and the lowest in CG (P<0.05). Fish that received diet supplemented with Se-NP, Zn-NP, and Se/Zn-NP significantly (P<0.05) increased superoxide dismutase and catalase while reduced malonaldehyde activity compared to CG. Intestinal morphometry revealed significantly (P<0.05) increased villi length and goblet cells number in fish fed with Se-NP and/or Zn-NP. In conclusion, dietary supplementation of Nile tilapia with Se-NP and Zn-NP induces synergistic effects that improve growth performance, blood health, and intestinal histomorphology., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC part of Springer Nature.)

An experiment was conducted to evaluate the effect of supplementation of zinc in the diet in the form of nano zinc oxide (nano ZnO) on the performance of broilers. A total of 240 day-old commercial broiler chicks were distributed in a completely randomized design into 6 treatments with 8 replicates of 5 chicks each. Treatments comprised of T 1 - basal diet (BD) without ZnO supplementation, T 2 - 2.5 ppm ZnO, T 3 - 5 ppm ZnO, T 4 - 10 ppm ZnO, T 5 - 20 ppm ZnO, and T 6 - 40 ppm inorganic ZnO. The results revealed that supplementation of nano ZnO at 2.5 ppm recorded significantly (P < 0.05) higher body weight gain, feed intake, and better feed conversion ratio (FCR) compared to control and other treatment groups at 42 days of age. All dietary treatments failed to exert any significant (P > 0.05) effect on various carcass parameters (dressing percentage, abdominal fat, giblet yields), serum protein and cholesterol concentrations, and meat quality parameters (water holding capacity and pH) of broiler chicken at 42 days of age. Finally, it could be concluded that supplementation of nano ZnO at 2.5 ppm improved the performance of broilers., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC part of Springer Nature.)

Mycogenic synthesis of medically applied zinc oxide (ZnO) and copper oxide (CuO) nanoparticles (NPs) were exploited using Penicillium chrysogenum. The biogenesis and capping processes of the produced nano-metals were conducted by functional fungal extracellular enzymes and proteins. The obtained ZnO-NPs and CuO-NPs were characterized. Also, the antibacterial activity and minimum inhibitory concentration (MIC) values of ZnO-NPs and CuO-NPs were determined. Also, antibiofilm and antifungal activities were investigated. Results have demonstrated the ability of the bio-secreted proteins to cape and reduce ZnO and CuO to hexagonal and spherical ZnO-NPs and CuO-NPs with particle size at 9.0-35.0 nm and 10.5-59.7 nm, respectively. Both ZnO-NPs and CuO-NPs showed high antimicrobial activities not only against Gram-positive and Gram-negative bacteria but also against some phytopathogenic fungal strains. Besides this, those NPs showed varied antibiofilm effects against different microorganisms. Quantitative and qualitative analyses indicated that CuO-NPs had an effective antibiofilm activity against Staphylococcus aureus and therefore can be applied in diverse medical devices. Thus, the mycogenic green synthesized ZnO-NPs and CuO-NPs have the potential as smart nano-materials to be used in the medical field to limit the spread of some pathogenic microbes.

Zinc oxide nanoparticles (ZnO-NPs) are used immensely in technology and medicine, but very less is known about toxicity mechanism to human epidermal cells. The objective of this study was to evaluate possible anticancer properties of ZnO-NPs on human epidermoid carcinoma cells using MTT assay, measurement of reactive oxygen species, DNA fragmentation, and nuclear condensation. ZnO-NPs were synthesized by sol-gel method using zinc acetate dihydrate, ethylene glycol, and 2-propyl alcohol. Numerous characterization techniques such as UV-visible spectroscopy, X-ray powder diffraction, transmission electron microscopy, and dynamic light scattering spectroscopy were used to confirm synthesis, purity, optical, and surface characteristics, size, shape, and distribution of ZnO-NPs. Our finding showed that ZnO-NPs considerably decreased cell viability of human epidermoid carcinoma A431 cells with a parallel increase in nuclear condensation and DNA fragmentation in a dose dependent manner. Moreover, real time PCR expression study showed that treatment of human epidermoid carcinoma cells with ZnO-NPs trigger increased expression of tumor suppressor gene p53, bax, and caspase-3 while downregulate antiapoptotic gene bcl-2. Thus ZnO-NPs induce apoptosis in A431 cells through DNA degradation and generation of reactive oxygen species via p53, bax/bcl-2, and caspase pathways.

This experiment was conducted to investigate the effects of zinc oxide/zeolite on growth performance, serum biochemistry, intestinal morphology, and microflora of weaned piglets. Two hundred and fifty-six weaned piglets (Duroc × Landrace × Large) at 21 days of age were randomly assigned to 2 groups with 8 replicates and 16 piglets in each pen. The diets of high dose of zinc oxide group (HD-ZnO) supplemented with 1500 mg/kg zinc as zinc oxide, but the diet of experimental group supplemented with 500 mg/kg zinc as zinc oxide that supported on zeolite (SR-ZnO). The experiment was conducted for 2 weeks after weanling. The results showed replacement of high-dosed zinc oxide by SR-ZnO had no significant effects on growth performance and intestinal morphology. However, the dietary supplementation of SR-ZnO reduced the diarrhea rate (P < 0.05), increased the activity of serum alkaline phosphatase (ALP) (P < 0.01), and tended to reduce zinc release in stomach (P = 0.06) and increase serum total protein (TP) (P = 0.07). Although there were no significant effects in ileal microflora on α diversity, the abundance of Campylobacters was found significantly decreased (P < 0.05), whereas the abundance of Clostridium was increased (P < 0.05) after lower-dosed SR-ZnO replacement. It is revealed that replacement of HD-ZnO (1500 mg/kg) by SR-ZnO (500 mg/kg) in creep feed could improve the zinc bioavailability, regulate the intestinal flora, and alleviate the postweaning diarrhea in weaned piglets. Accordingly, the application of SR-ZnO would reduce the zinc in feed and therefore benefits for the ecological environment.

The purposes of this work are to evaluate the antimicrobial, antibiofilm, anticancer, and antioxidant abilities of anisotropic zinc oxide nanoparticles (ZnO NPs) synthesized by a cost-effective and eco-friendly sol-gel method. The synthesized ZnO NPs were entirely characterized by UV-Vis, XRD, FTIR, HRTEM, zeta potential, SEM mapping, BET surface analyzer, and EDX elemental analysis. Antimicrobial and antibiofilm activities of ZnO NPs were investigated against multidrug-resistant (MDR) bacteria and yeast causing serious diseases like urinary tract infection (UTI). The anticancer activity was performed against Ehrlich ascites carcinoma (EAC). Additionally, antioxidant scavenging activity against 2,2-diphenyl-1-picrylhydrazyl (DPPH) was observed. The synthesized ZnO NPs exhibited an absorption peak at 385.0 nm characteristic to the surface plasmon resonance (SPR). Data obtained from HRTEM, SEM, and XRD confirmed the anisotropic crystalline nature of the prepared ZnO NPs with an average particle size of 68.2 nm. The calculated surface area of the prepared ZnO NPs was 10.62 m 2 /g and the porosity was 13.16%, while pore volume was calculated to be 0.013 cm 3 /g and the average pore size was about 3.10 nm. The prepared ZnO NPs showed promising antimicrobial activity against all tested UTI-causing pathogens. It showed a prominent antimicrobial capability against Candida tropicalis with a zone of inhibition (ZOI) reaching 22.4 mm, 13 mm ZOI for Bacillus subtilis, and 12.5 mm ZOI for Pseudomonas aeruginosa. Additionally, the prepared ZnO NPs showed enhanced biofilm repression of about 79.33%, 72.94%, and 33.68% against B. subtilis, C. tropicalis, and P. aeruginosa, respectively. Moreover, the prepared ZnO NPs had a powerful antioxidant property with 33.0% scavenging ability after applied DPPH assay. Surprisingly, upon ZnO NPs treatment, cancer cell viability reduced from 100 to 58.5% after only 24 h due to their unique antitumor activity. Therefore, according to these outstanding properties, this study could give insights for solving serious industrial, pharmaceutical, and medical challenges, particularly in the EAC and UTI medications.

Zinc deficiency in aquatic animals affects the biological processes and physiological functions. Thus, the supplement of ZnONPs can be used as an alternative method to overcome zinc deficiency. Nanoparticles have the potential to enhance the growth and health of the fish. The main aim of this study is to evaluate the growth efficacy of ZnONP-supplemented diet with fingerlings of Labeo rohita. The green synthesized ZnONPs were characterized by ultraviolet-visible (UV-Vis) spectroscopy, Fourier transformer infrared spectroscopy (FTIR), X-ray diffraction (XRD), scanning electron microscopy (SEM), and energy dispersive spectroscopy (EDS). Different concentrations of ZnONPs (5, 7.5, and 10 mg/kg) were administered in the basal diet of freshwater fish Labeo rohita for 45 days to observe the growth and metabolic functions of the body. However, the fish fed with 10 mg/kg ZnONP-supplemented diet shows that the growth performance was highly increased followed by 7.5 mg/kg and 5 mg/kg ZnONPs when compared with the control. The biochemical, hematological, and digestive enzyme activities were also significantly increased with different concentrations of ZnONPs. The effects of zinc oxide nanoparticles show the higher improvement of growth and metabolic functions in Labeo rohita. These results suggest that the nanotechnology could apply for feed formulation technology and pave the way for the dietary supplementation of zinc oxide nanoparticles as safe ingredients for aquatic animals to overcome the zinc deficiency.

A study was conducted to validate the effects of nano form of zinc (NZn) on nutrient digestibility, zinc retention, organ and serum zinc profile, and hepatic metallothionein gene expression in Wistar albino rats (WAR). Nano zinc (NZn) was synthesized through chemical method, by using 0.45 M zinc nitrate [Zn(NO 3 ) 2 .6H 2 O] and 0.9 M sodium hydroxide (NaOH). The NZn particle in its oxide form was characterized by TEM-EDAX and XRD, and found to be in nano range (below 100 nm. Zinc was supplemented to the Wistar albino rats (WAR) through synthetic semi-purified diet either without Zn, or as inorganic zinc (IZn; 25 mg/kg), or as synthesized NZn (25, 12.5, 6.25, 3.125 or 50 mg/kg DM) for 60 days. The zinc content was observed to be significantly (P < 0.05) higher in liver, bone, kidney, and serum due to NZn supplementation where NZn-50 had highest zinc content and control had the least, without affecting Fe, Mn, and Cu. NZn at 12.5 mg/kg group rats were either comparable or better than IZn at 25 mg/kg in terms of zinc retention, CP digestibility, zinc level in serum, liver, bone, and kidney suggesting its better bioavailability simultaneously also reduced fecal excretion of zinc to the environment. Metallothionein mRNA expression was upregulated in NZn at 25 mg/kg and NZn at 50 mg/kg than IZn at 50 mg/kg. Thus, in WAR, NZn at half of the ICAR recommendation (25 mg/kg DM) is as effective as inorganic zinc at 100% of recommended dose.

This study was conducted to investigate effects of dietary zinc oxide nanoparticles (nano-ZnOs) on growth, diarrhea rate, mineral deposition (Zn, Fe, and Mn), intestinal morphology, and barrier of weaned piglets. A total of 384 weaned piglets (Duroc × Landrace × Yorkshire) in 4 groups were fed a basal diet supplemented with 0, 400, and 800 mg/kg nano-ZnOs or 3000 mg/kg ZnO for 14 days. Compared with the control group, 800 mg/kg nano-ZnOs and 3000 mg/kg ZnO significantly increased average daily gain and decreased diarrhea rate of weaned piglets. There was no significant difference among ZnO and nano-ZnO groups. ZnO and nano-ZnOs did not affect serum activities of glutamic oxalacetic transaminase, glutamic-pyruvic transaminase, and lactate dehydrogenase. However, ZnO and 800 mg/kg nano-ZnOs significantly increased zinc concentrations in plasma, liver, pancreas, and tibia, without affecting Fe and Mn concentrations. Compared with the control group, 800 mg/kg nano-ZnOs significantly reduced plasma diamine oxidase activity, decreased total aerobic bacterial population in mesenteric lymph node, enhanced mRNA expressions of occludin, ZO-1, IL-1β, IL-10, TNF-α, and ki67 in ileal mucosa, and increased villous height, width, crypt depth, and surface area. Compared to ZnO group, 800 mg/kg nano-ZnOs significantly decreased aerobic bacterial population, enhanced mRNA expressions of occludin, IL-1β, IL-10, and TNF-α, and reduced fecal zinc concentration. These results indicated that 800 mg/kg nano-ZnOs might be a potential substitute for 3000 mg/kg ZnO in diets of weaned piglets.

The objective of this study was to evaluate the effectiveness of dietary zinc oxide (ZnO) and zinc methionine (Zn-Met) supplementation on layer performance, quality of egg, some blood constituents, and oxidative status in blood of laying hens. A total of 120 laying hens (Hisex Brown) 22-week-old were indiscriminately allotted into five groups of 24 hens with six replications (four birds/replicate). A complete randomized design experiment was performed including control (basal diet), two levels of ZnO (50 and 100 mg/kg basal diet), and two levels of Zn-Met (50 and 100 mg/kg basal diet) through 22 to 34 weeks of age. Supplementation of 100 mg of Zn-Met significantly (P = 0.001) increased feed intake compared to other treatment groups. The groups supplemented with 50 mg of ZnO and 100 mg of Zn-Met reported the significantly higher egg production rate (P = 0.002) and egg mass (P < 0.001) compared to other treated groups. All traits of egg quality were not statistically (P < 0.05 or 0.01) affected by ZnO or Zn-Met supplementation except shell thickness, Haugh unit score, and yolk to albumin ratio. Dietary supplementation of either ZnO or Zn-Met did not affect the oxidative parameters in serum except the activity of Cu-Zn-SOD. Serum triglyceride, total cholesterol, and LDL cholesterol (low-density lipoprotein) were significantly (P < 0.05) affected by Zn supplementation, while HDL cholesterol (high-density lipoprotein) did not affect. Compared to the control group, supplementation of ZnO or Zn-Met increased serum content of zinc with no differences among supplemental zinc doses. It could be concluded that dietary inorganic (ZnO) and organic (Zn-Met) supplemented up to 50 and 100 mg/kg, respectively, can be used as effective supplements to improve productivity of laying hens, serum zinc level, lipid profile (triglyceride and LDL cholesterol), and activity of Cu-Zn-SOD.

In the present study, toxicity of commercial zinc oxide nanoparticles (ZnO NPs) was studied on the bacterium Pseudomonas sp., human promyelocytic leukemia (HL-60) cells, and peripheral blood mononuclear cells (PBMC). The toxicity was assessed by measuring growth, cell viability, and protein expression in bacterial cell. The bacterial growth and viability decreased with increasing concentrations of ZnO NP. Three major proteins, ribosomal protein L1 and L9 along with alkyl hydroperoxides reductase, were upregulated by 1.5-, 1.7-, and 2.0-fold, respectively, after ZnO NP exposure. The results indicated oxidative stress as the leading cause of toxic effect in bacteria. In HL-60 cells, cytotoxic and genotoxic effects along with antioxidant enzyme activity and reactive oxygen species (ROS) generation were studied upon ZnO NP treatment. ZnO NP exhibited dose-dependent increase in cell death after 24-h exposure. The DNA-damaging potential of ZnO NP in HL-60 cells was maximum at 0.05 mg/L concentration. Comet assay showed 70-80% increase in tail DNA at 0.025 to 0.05 mg/L ZnO NP concentration. A significant increase of 1.6-, 1.4-, and 2.0-fold in ROS level was observed after 12 h. Genotoxic potential of ZnO NPs was also demonstrated in PBMC through DNA fragmentation. Thus, ZnO NP, besides being an essential element having antibacterial activity, also showed toxicity towards human cells (HL-60 and PBMC).

Due to their small size, zinc oxide (ZnO) nanoparticles (NPs) are readily absorbed and easily cross biological barriers, which make them promising candidates as diet additives. However, some studies have reported that ZnO NPs cause toxicity; therefore, their safety and potency as diet additives for farm animals should be established. This study was the first to fully evaluate the effects of ZnO NPs on the homeostasis of eight elements in seven organs/tissues. The regulation of element homeostasis was found to be organ specific with no influence on oxidation status, anti-oxidation capability, or organ damage. ZnO NPs may specifically regulate the homeostasis of mineral elements and affect the following correlations: (1) between the element content in each organ and the concentration of Zn used in ZnSO 4 or ZnO NP treatments; (2) between ZnO NP and ZnSO 4 treatments for the same element in each organ; and (3) between elements (in each organ in ZnSO 4 or ZnO NP treatments) in layers' organs/tissues. The use of ZnO NPs as diet additives for animals should be implemented cautiously because, among other uncertainties, they may affect mineral element content.

The current study was conducted to investigate the effects of dietary zinc oxide (ZnO) on the antioxidant capacity, small intestine development, and jejunal gene expression in weaned piglets. Ninety-six 21-day-old piglets were randomly assigned to three dietary treatments. Each treatment had eight replicates with four piglets per replicate. The piglets were fed either control diet (control) or control diet supplemented with in-feed antibiotics (300 mg/kg chlortetracycline and 60 mg/kg colistin sulfate) or pharmacological doses of ZnO (3000 mg/kg). The experiment lasted 4 weeks. Blood samples were collected at days 14 and 28, while intestinal samples were harvested at day 28 of the experiment. Dietary high doses of ZnO supplementation significantly increased the body weight (BW) at day 14 and average daily gain (ADG) of days 1 to 14 in weaned piglets, when compared to control group (P < 0.05). The incidence of diarrhea of piglets fed ZnO-supplemented diets, at either days 1 to 14, days 14 to 28, or the overall experimental period, was significantly decreased in comparison with those in other groups (P < 0.05). Supplementation with ZnO increased the villus height of the duodenum and ileum in weaned piglets and decreased the crypt depth of the duodenum, when compared to the other groups (P < 0.05). Dietary ZnO supplementation decreased the malondialdehyde (MDA) concentration at either day 14 or day 28, but increased total superoxide dismutase (T-SOD) at day 14, when compared to that in the control (P < 0.05). ZnO supplementation upregulated the messenger RNA (mRNA) expression of zonula occludens-1 (ZO-1) and occludin in the jejunum mucosa of weaned piglets, compared to those in the control (P < 0.05). The pro-inflammatory cytokine interleukin-lβ (IL-1β) mRNA expression in the jejunum mucosa was downregulated in the ZnO-supplemented group, compared with the control (P < 0.05). Both in-feed antibiotics and ZnO supplementation decreased the mRNA expression of interferon-γ (IFN-γ), but increased the mRNA expression of transforming growth factor-β (TGF-β), in the jejunum mucosa of piglets, when compared to those in the control (P < 0.05). In summary, supplemental ZnO was effective on the prevention of post-weaning diarrhea (PWD) in weaned piglets and showed comparative growth-promoting effect on in-feed antibiotics, probably by the mechanism of improvement of the antioxidant capacity, restoration of intestinal barrier function and development, and modulation of immune functions.

The zinc oxide (ZnO) nanoparticle has been widely used in biomedical applications and cancer therapy and has been reported to induce a selective cytotoxic effect on cancer cell proliferation. The present study investigated the cytotoxicity of ZnO nanoparticles against co-cultured C2C12 myoblastoma cancer cells and 3T3-L1 adipocytes. Our results showed that the ZnO nanoparticles could be cytotoxic to C2C12 myoblastoma cancer cells than 3T3-L1 cells. The messenger RNA (mRNA) expressions of p53 and bax were significantly increased 114.3 and 118.2 % in the C2C12 cells, whereas 42.5 and 40 % were increased in 3T3-L1 cells, respectively. The mRNA expression of bcl-2 was reduced 38.2 and 28.5 % in the C2C12 and 3T3-L1 cells, respectively, whereas the mRNA expression of caspase-3 was increased 80.7 and 51.6 % in the C2C12 and 3T3-L1 cells, respectively. The protein expressions of p53, bax, and caspase-3 were significantly increased 40, 81.8, and 80 % in C2C12 cells, whereas 20.3, 28.2, and 37.9 % were increased in 3T3-L1 cells, respectively. The mRNA expression of bcl-2 was significantly reduced 32.2 and 22.7 % in C2C12 and 3T3-L1 cells, respectively. Caspase-3 enzyme activity and reactive oxygen species (ROS) were increased in co-cultured C2C12 cells compared to 3T3-L1 cells. Taking all these data together, it may suggest that ZnO nanoparticles severely induce apoptosis in C2C12 myoblastoma cancer cells than 3T3-L1 cells.

Although toxic effects of zinc oxide nanoparticles (ZnO NPs) have been previously studied, there are still controversies in terms of dose, size, shape, and affecting cells. By such a perspective, in this study, small size of ZnO NPs with a diameter of 10 nm at low concentrations was studied for any effect on the viability and function of isolated rat pancreatic islets. Islets of Langerhans were isolated and assessed for viability, functionality (insulin secretion), cytosolic reactive oxygen species (ROS), and apoptosis by flow cytometry. The LC50 of ZnO NPs was found at 1,400 ng/mL at the first phase of the study. A meaningful increase in viability of islets and insulin secretion in basal and even stimulated concentrations of glucose was found by ZnO NPs (70 ng/mL) with p < 0.001 and p < 0.05, respectively. Likewise, ZnO NPs in 70 ng/mL concentration decreased cytosolic ROS generation (p < 0.05). In the meantime, the percentage of early stage of apoptotic cells dropped down to 17 % (from 29 % of control). These results for the first time confirm that ZnO NPs are not only safe when used at dose of 70 ng/mL but also improve viability and function of pancreatic islets and meanwhile reduce oxidative stress and prevent cells from entering the apoptotic phase.

Broilers in four groups were fed a basal diet supplemented with 60 mg/kg zinc oxide (60-ZnO; control), or 20, 60, or 100 mg/kg ZnO nanoparticles (20-, 60-, and 100-nano-ZnO, respectively). Compared with the controls, after 14 days, birds in the 20- and 60-nano-ZnO groups had significantly greater weight gains and better feed conversion ratios. However, the body weight of birds in the 100-nano-ZnO group was dramatically reduced after 28 days. Relative to the control group, the total antioxidant capability (T-AOC) in serum and liver tissue was significantly higher in the 20-nano-ZnO group at all time points and also significantly higher in the 60- and 100-nano-ZnO groups in serum on days 28 and 35 and in liver tissues on days 21 and 28. Compared with the controls, the activity of copper-zinc superoxide dismutase (Cu-Zn-SOD) was significantly greater in the 60- and 100-nano-ZnO groups in serum on days 28 and 35 and in liver tissues after 21 days. Catalase activity in serum samples was significantly higher in the 20- and 60-nano-ZnO groups relative to the control and 100-nano-ZnO birds, but catalase activity in liver tissue was not affected by different nano-ZnO levels. Malondialdehyde content in serum and liver tissues was significantly reduced in the 20-, 60-, and 100-nano-ZnO groups compared with that in the control group at all time points except day 42. Taken together, our data indicate that appropriate concentration of dietary ZnO nanoparticles improves growth performance and antioxidative capabilities in broilers, and 20 mg/kg nano-ZnO is the optimal concentration.

Zinc oxide nanoparticles (ZnO NPs) can be ingested directly when used in food, food packaging, drug delivery, and cosmetics. This study evaluated the cellular effects of ZnO NPs (50 and 100 nm diameter particle sizes) on the function of osteoblastic MC3T3-E1 cells. ZnO NPs showed cytotoxicity at concentrations of above 50 μg/ml, and there was no significant effect of the size on the cytotoxicity of ZnO NPs. Within the testing concentrations of 0.01~1 μg/ml, which did not cause a marked drop in cell viability, ZnO NPs (0.1 μg/ml) caused a significant elevation of alkaline phosphatase activity, collagen synthesis, mineralization, and osteocalcin content in the cells (P < 0.05). Moreover, pretreatment with ZnO NPs (0.01~1 μg/ml) significantly reduced antimycin A-induced cell damage by preventing mitochondrial membrane potential dissipation, complex IV inactivation, and ATP loss. Measurement of reactive oxygen species (ROS) indicated decrease in ROS level upon exposure to ZnO nanoparticles (0.01 μg/ml). Hence, our study indicated that ZnO nanoparticles can have protective effects on osteoblasts at low concentrations where there are little or no observable cytotoxic effects.

Zinc has been shown to be an inhibitor of apoptosis for many years. The present study was designed to investigate effects of three zinc chemical forms on H2O2-induced cell apoptosis in IEC-6 cells via analysis of cell vitality, LDH activity, apoptosis percentage, caspase-3 activity, and Bcl-2, Bax, and caspase-3, -8, and -9 gene expression. Cells were divided into H2O2 and zinc sources+H2O2 groups, and there are three different zinc sources [zinc oxide nanoparticle (nano-ZnO), zinc oxide (ZnO), and zinc sulfate (ZnSO4)] and three concentrations (normal = 25 μM, medium = 50 μM, and high = 100 μM) used in this article. In the present study, we found the striking cytotoxicity of H2O2 higher than 200 μM on cell vitality, LDH activity, and apoptosis percentage in the cells using five different concentrations (50, 100, 200, 400, and 800 μM) of H2O2 for 4 h. Moreover, we observed that cell vitality was increased, LDH activity and apoptotic percentage were decreased, and gene expression level of Bax and caspase-3 and -9 was markedly reduced, while gene expression level of Bcl-2 and ratio of Bcl-2/Bax were increased in normal concentration groups of nano-ZnO and ZnSO4 compared with H2O2 group, but no significant difference was observed in caspase-8 gene expression. Furthermore, medium or, more intensely, high concentrations of nano-ZnO and ZnSO4 enhanced H2O2-induced cell apoptosis. Compared with nano-ZnO and ZnSO4, ZnO showed weakest protective effect on H2O2-induced apoptosis at normal concentration and was less toxic to cells at high level. Taken together, we proposed that preventive and protective effects of zinc on H2O2-induced cell apoptosis varied in IEC-6 cells with its chemical forms and concentrations, and maybe for the first time, we suggested that nano-ZnO have a protective effect on H2O2-induced cell apoptosis in IEC-6 cells.

Pharmacological dietary zinc (Zn) concentrations of 1,000 to 3,000 mg/kg diet from Zn oxide have been found to increase growth in post-weaning pigs. However, results were inconsistent among studies. A frequentist meta-analysis, in which effects were numerically described with standardized effect sizes (Hedges's g), was conducted in order to identify and quantify the responses in average daily gain (ADG), average daily feed intake (ADFI), and gain to feed ratio (G/F) in post-weaning pigs upon dietary Zn supplementation from Zn oxide. The inability of independent continuous variables to explain significant heterogeneity obtained with fixed effect models necessitated the use of random effects models to calculate summary statistics. Dietary Zn supplementation increased (P < 0.05) ADG (mean effect size = 1.086, 95 % confidence intervals = 0.905-1.266, 26 studies, 72 comparisons), ADFI (mean effect size = 0.794, 95 % confidence intervals = 0.616-0.971, 25 studies, 71 comparisons), and G/F (mean effect size = 0.566, 95 % confidence intervals = 0.422-0.710, 24 studies, 70 comparisons). Zinc oxide provided a feasible alternative to in-feed antibiotics to improve growth in post-weaning pigs, and its reduction in diets due to potential environmental pollution will have to be negated by alternative feed additives and management strategies in order to prevent economic losses.

This experiment was conducted to evaluate the effect of zinc, manganese, and copper sources (inorganic vs. organic) in the diet on laying performance and eggshell quality characteristics. One hundred and eighty Hy-Line W-36 layers at 38 weeks of age were allocated to 36-layer cages of five hens each. Each six cages were randomly assigned to one of the six experimental diets fed from 38 to 53 week of age. In three experimental treatments, the basal diet was supplemented with 65-75-7 or 65-75-7 or 40-40-7 mg/kg of Zn, Mn, and Cu, respectively, from their oxide or sulfate sources. Three other groups were fed diets supplemented with 20-20-3.5 or 40-40-7.5 or 60-60-10.5 mg/kg of organic forms of Zn, Mn, and Cu, respectively. Dietary treatments significantly did affect feed intake (P < 0.001), feed conversion ratio (P < 0.001) and percentage of broken eggs (P < 0.05). Substitution of Zn and Mn oxides (65 and 75 mg kg(-1), respectively) with equal amounts of their sulfate forms significantly improved feed intake, feed conversion ratio, percentage of broken eggs, and Haugh Unit (P < 0.05). In addition, laying hens maintained their performance when substitution of Zn and Mn oxides and Cu sulfate (65, 75, and 7 mg kg(-1), respectively) reduced up to 20, 20, and 3.5 mg kg(-1) by amino acid complexes of the microelements. The results showed that a corn-soybean diet supplemented with the organic forms of Zn, Mn, and Cu at a dosage 50% to 75% lower than NRC recommendation is sufficient to maintain laying performance and can improve eggshell and albumen qualities of the egg in laying hens.