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Aim: This work was performed to investigate the pharmacokinetics of the triamilide antibiotic, tulathromycin in healthy rabbits. Materials and Methods: Ten rabbits in each group were given a single dose of 2.5 mg/kg body weight (bw) of tulathromycin via intravenous (IV), intramuscular (IM) and subcutaneous (SC) administrations. The concentration of tulathromycin in plasma was determined by microbiological assay Bacillus subtilis ATCC6633 as the test organism. Results: Following IV administration, the total body clearance (Cltot) was 321.70 ml/kgh, the volume of distribution at steady-state (Vdss) was 13.26 L/kg and the value of the elimination half-life (t1/2β) was 29.29 h. After SC administration, the elimination half-life (t1/2el), mean residence time (MRT) and maximum plasma concentration (Cmax) were significantly higher (36.22 h, 52.54 h and 882.19 ng/ml) than after IM route (31.69 h, 45.89 h and 714.72 ng/ml), respectively. Tulathromycin was bound to the extent of 36% to plasma protein of healthy rabbits. The absolute bioavailabilities were 88.07 and 94.25% after IM and SC injections. Conclusion:Thus a single dose of tulathromycin is promising treatment for most respiratory disease in rabbits. [ABSTRACT FROM AUTHOR]

The Pharmacokinetic aspects of flunixin (FL) administered alone and in combination with enrofloxacin (EN), were studied in clinically healthy calves. The experiments were performed on two groups: FL alone (2.2 mg/kg, intramuscular (IM)), and combination of FL (2.2 mg/kg, IM) and EN (2.5 mg/kg, IM). Plasma concentrations of FL were determined using High Performance Liquid Chromatography (HPLC) method. Moreover, the effects of FLaloneor in combination on liver and kidney functions were also assessed. Flunixin was rapidly absorbed intramuscularly with a half-life of absorption (t ) of 0.094 h and the peak plasma concentration (C ) was 1.27 g/mLwas attained after 1/2ab max 0.49 h (T ). Enrofloxacin significantly altered the pharmacokinetics of FLby delaying its absorption and accelerate its max elimination from body. Significant increases (32%) in the area under the curve (AUC) and (37%) in the elimination rate constant (K ) from the central compartment and a significant decrease (27%) in the elimination half-life (t ) of FL el 1/2el were found following coadministration with EN, compared with administration of FL alone. The maximum plasma drug concentration (C ) showed significant increase(28%) following the coadministration of EN with FL as max compared to that following the administration of FL alone. It was concluded that the combination of FL and EN negatively altered the kinetics of FL and exaggerated the adverse effect on hepato-renal function in calves consequently; theconcomitant use of FL and EN should be avoided in calves. [ABSTRACT FROM AUTHOR]

Abo-El-Sooud, K., Goudah, A. Influence of Pasteurella multocida infection on the pharmacokinetic behavior of marbofloxacin after intravenous and intramuscular administrations in rabbits. J. vet. Pharmacol. Therap. 33, 63–68. The pharmacokinetic behavior of marbofloxacin was studied in healthy ( n = 12) and Pasteurella multocida infected rabbits ( n = 12) after single intravenous (i.v.) and intramuscular (i.m.) administrations. Six rabbits in each group (control and diseased) were given a single dose of 2 mg/kg body weight (bw) of marbofloxacin intravenously. The other six rabbits in each group were given the same dose of the drug intramuscularly. The concentration of marbofloxacin in plasma was determined using high-performance liquid chromatography. The plasma concentrations were higher in diseased rabbits than in healthy rabbits following both routes of injections. Following i.v. administration, the values of the elimination half-life ( t1/2β), and area under the curve were significantly higher, whereas total body clearance was significantly lower in diseased rabbits. After i.m. administration, the elimination half-life ( t1/2el), mean residence time, and maximum plasma concentration ( Cmax) were higher in diseased rabbits (5.33 h, 7.35 h and 2.24 μg/mL) than in healthy rabbits (4.33 h, 6.81 h and 1.81 μg/mL, respectively). Marbofloxacin was bound to the extent of 26 ± 1.3% and 23 ± 1.6% to plasma protein of healthy and diseased rabbits, respectively. The Cmax /MIC (minimum inhibitory concentration) and AUC/MIC ratios were significantly higher in diseased rabbits (28 and 189 h) than in healthy rabbits (23 and 157 h), indicating the favorable pharmacodynamic characteristics of the drug in diseased rabbits. [ABSTRACT FROM AUTHOR]

Purpose: The antibacterial properties of silver nanoparticles (AgNPs) are extensively identified. In large quantities, they might be harmful. So many fields of nanotechnology have shown a great deal of interest in the development of an environmentally friendly, efficient method for synthesizing metal nanoparticles. Because of its antibacterial and antifungal properties toward a wide range of microbes, chitosan silver nanoparticles (AgNPs@Cs) constitute a newly developing class of bio-nanostructured hybrid materials. Furthermore, the use of photothermal therapy (PTT) has been suggested as a means of elimination of germs. These light-stimulated treatments are minimally invasive and have a few side effects. In the present work, the antibacterial effect of AgNPs at low concentrations; prepared by chemical and green methods as antimicrobial and photothermal agents in photothermal therapy; with laser irradiation were explored as combined treatment against MRSA, Pseudomonas aeruginosa, and Klebsiella pneumoniae., Methods: Silver nanoparticles were produced in two ways. First, by sodium borohydrides, second, by chitosan (as a natural eco-friendly reducing, and capping agent). The nanostructure of AgNPs and AgNPs@Cs was confirmed by UV-visible spectrometer, transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FTIRs), and direct light scattering (DLS). The antibacterial activity of the prepared nanoparticles and the laser irradiation was tested against three bacterial species of zoonotic importance; MRSA, Pseudomonas aeruginosa, and Klebsiella pneumoniae; and was evaluated by measuring their minimum inhibitory concentrations (MIC)., Results: Silver nanoparticles produced by the two methods had spherical shapes with nearly the same particle size. The analysis of DLS showed that AgNPs were very stable with zeta potential - 28.8 mv, and 47.7 mv by chemical and chitosan synthesis, respectively. Furthermore, AgNPs@Cs showed higher antibacterial activity toward the tested bacterial species than AgNPs by chemical method. Additionally, the bacterial viability using photothermal laser therapy was reduced compared to laser and AgNPs alone. The bactericidal activities were higher when laser diode was coupled with AgNPs@Cs than by chemical reduction., Conclusion: The laser combined treatment had a higher antimicrobial effect than AgNPs alone or laser irradiation alone., (© 2024. The Author(s).)

This study investigated the effects of in-ovo inoculation of betaine on hatchability, hatching weight, and intestinal development, as well as serum and expression levels of some antioxidants in the posthatched chicks. A total of 350 fertile eggs of Hubbard efficiency plus breeder's flock were incubated at normal incubation temperature (37.5°C) and randomly assembled into 3 groups with 4 replicates, and 25 eggs per each. The experimental groups were allocated as noninjected control group (CN), diluent-injected group (CP, 0.1 mL saline), and betaine-injected group (B, 2.5 mg in 0.1 mL saline). The injections were performed in the air cells of the eggs on the 12th day of the embryonic phase. Hatchability percentage, hatching weight, serum-reduced glutathione (GSH), and superoxide dismutase (SOD) were estimated in 7-day-old chicks. Moreover, expression levels of the nuclear factor erythroid 2-related factor 2 (Nrf2) and SOD were determined in the breast skeletal muscles of chicks. Jejunum histo-morphometric analysis was assessed with computerised morphometric measurements. The results revealed that the hatchability percentage was not influenced by in-ovo injection of betaine or vehicle while betaine significantly increased the hatchling's weight of chicks. Moreover, there were a significant increase in SOD and Nrf2 mRNA expression levels. In-ovo injection of betaine significantly induced positive effects on intestinal morphometry by ameliorating the jejunal villus length, the ratio of villus height to villus width, and absorptive surface area., (© 2024 Wiley‐VCH GmbH. Published by John Wiley & Sons Ltd.)

The current study compared the effects of incorporated exposure to arsenic trioxide (As) and zinc oxide nanoparticles (ZnONPs) on male reproductive hormones, oxidative stress, and inflammatory biomarkers in adult rats to each metal alone. A defensive trial with gallic acid (GA) has also been studied. A total of 60 adult male Sprague Dawley rats were categorized into six groups: control, GA (20 mg/kg), ZnONPs (100 mg/kg), As (8 mg/kg), ZnONPs with As, and GA concurrently with ZnONPs and As at the same previous doses. The regimens were applied for 60 days in sequence. Current findings showed significant weight loss in all study groups, with testicular weights significantly decreased in the As and combined groups. Testosterone, follicular stimulating hormone, and luteinizing hormone serum levels were also considerably reduced, while serum levels of estradiol increased. Inducible nitric oxide synthase (iNOS) immunoexpression was significantly upregulated while proliferating cell nuclear antigen (PCNA) was downregulated. Moreover, there was a significant elevation of testicular malondialdehyde, reduction of testicular superoxide dismutase, and glutathione peroxidase with disruptive testes, prostate glands, and seminal vesicle alterations in all experimental groups with marked changes in the combined group. Additionally, the present results revealed the protective effects of GA on ZnONPs and As adverse alterations in rats. GA enhanced sperm picture, oxidant status, and hormonal profile. Also, it modulates iNOS and PCNA immunoexpression and recovers the histoarchitecture of the testes, prostate glands, and seminal vesicles. Ultimately, GA may be a promising safeguarding agent against ZnONPs and As-induced disturbances to reproductive parameters., (© 2024. The Author(s).)

Aim of the Work: The study was conducted to evaluate the influence of theophylline pre-treatment on serum pharmacokinetics and milk elimination of tylosin following single intramuscular (IM) administrations in lactating goats., Methods and Results: In a cross-over study, tylosin was injected via intramuscular (IM) at a single dose of 15 mg/kg b.wt. After a one-month washout period goats received theophylline at a daily IM dose of 2 mg/kg b.wt. for seven consecutive days then tylosin was injected IM dose of 15 mg/kg b.wt. two hours after the last theophylline dosing. Blood samples were collected before and at 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10, 12, and 24 h post-injection. Samples were left to clot and then centrifuged to yield serum. Milk samples were collected before and at 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 48, and 72 h post-injection from each goat by hand milking. Tylosin serum concentrations were determined by high-performance liquid chromatography (HPLC). Tylosin concentrations versus time were analyzed by a noncompartmental method. Tylosin C max significantly declined from 1.73 ± 0.10 to 1.01 ± 0.11 µg/ml, and attained T max values of 2 and 1 h, respectively in theophylline-pretreated goats. Moreover, theophylline pretreatment significantly shortened the elimination half-life (t 1/2el ) from 6.94 to 1.98 h, t 1/2ka from 0.62 to 0.36 h and the mean residence time (MRT) from 8.02 to 4.31 h, also Vz/F and AUCs decreased from 11.91 to 7.70 L/kg and from 12.64 to 4.57 µg*h/ml, respectively, consequently, theophylline enhanced the clearance (Cl/F) of tylosin from the body. Similarly, tylosin milk concentrations were significantly lower in theophylline-pretreated goats than in goats that received tylosin alone and were detected up to 24 and 72 h in both groups, respectively. Moreover, the t 1/2el and AUCs were significantly decreased from 14.68 ± 1.97 to 4.72 ± 0.48 h, and from 181 to 67.20 µg*h/ml, respectively., Conclusions: The withdrawal period for tylosin in goat milk is at least 72 h. Theophylline pretreatment significantly decreases serum and milk tylosin concentrations to subtherapeutic levels, which could have serious clinical consequences such as failure of therapy. This means that after administering tylosin to goats, milk from these animals should not be consumed for at least 96 h to ensure that the milk is free from residues of the antibiotic., (© 2024. The Author(s).)

Background: Feed additives are products used in poultry nutrition to improve the quality of feed and the safety of food byproducts from animal origin. They are promising antibiotic alternatives for the production of broilers., Aim: This study aimed to investigate the effect of sodium butyrate (SB) and RL on growth performance, biochemical profile, immunity, and carcass traits of broilers., Methods: Five hundred-one-day-old chicks of the Hubbard breed were reared on floor pens in a privet farm, Giza. The chicks were weighed on arrival (each chick weighted 43-45 gm) and randomly assigned into five equal groups, with four replicates each (25 chicks/replicate). Group 1 was fed on a broiler diet without any additions (control). The diets of groups 2 and 3 were supplemented with 500 g/ton SB and 4 kg/ton RL, respectively. In group 4, the diet was enriched with 250 g/ton SB plus 2 kg/ton RL. Chicks in group 5 were fed on a diet fortified with 500 g/ton SB plus 4 kg/ton RL., Results: Supplementation of broiler diet with 500 g/ton SB plus 4 kg /ton RL increased body weight gain (BWG) and feed efficiency ratio (FER) of birds. It decreased serum levels of aspartate aminotransferase, alanine aminotransferase, total cholesterol triglycerides, and malondialdehyde, but increased superoxide dismutase, catalase, and immunoglobulins, phagocytic activity, lysozyme activity, and nitric oxide concentrations. Antibody titers against the Newcastle disease virus were also elevated., Conclusion: Supplementation of broiler diet with 500 g/ton SB plus 4 kg/ton RL gives the best result regarding productive efficiency and immunity of broiler chickens., Competing Interests: All authors declare that there are no conflicts of interest.

Background and Objectives: Little is known about the implications of titanium dioxide nanoparticles (TiO 2 NPs) and cadmium chloride (Cd) co-exposure on the male reproductive system in mammals. As a result, this study researched the effects of oral TiO 2 NPs and/or Cd exposure on male reproduction and testicular functions. Additionally, a mitigation trial with co-enzyme Q10 (CoQ10) has also been conducted., Methods: In a 60-day experiment, seven experimental groups, each containing 10 male Sprague Dawley rats, were orally given distilled water (control), corn oil (vehicle control), CoQ10 (10 mg/kg b.wt), TiO 2 NPs (50 mg/kg b.wt), Cd (5 mg/kg b.wt), TiO 2 NPs + Cd, and TiO 2 NPs + Cd + CoQ10. Then, sperm quality, male sex hormones, oxidative stress indications, Ti and Cd testicular residues, testes and accessory gland architecture, and apoptotic and inflammatory markers in rat testes were assessed., Results: TiO 2 NPs and/or Cd exposure negatively impacted body weight, weight gain, testicular weights, semen quality, serum reproductive hormones, oxidative stress parameters, and Caspase-3 and tumor necrosis factor (TNF-α) immunoreactions. Histopathological changes were recorded in testicular, seminal vesicle, and prostatic tissues. Yet, co-administration of CoQ10 with TiO 2 NPs and Cd substantially mitigated these adverse consequences. The most notable aspect is that it effectively lowered testicular tissue Ti and Cd levels. It also improved oxidant status, hormonal profile, and sperm picture. CoQ10 minimized the testicular damage implied by histological examination. Furthermore, CoQ10 significantly diminished TiO 2 NPs and Cd-induced Caspase-3 and TNF-α immunoexpression in testicular tissue., Conclusion: As a result, CoQ10 could be utilized as a safe remedy to protect male reproductive physiology from TiO 2 NPs and Cd damage., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

This study investigated the effect of oral dosing of titanium dioxide nanoparticles (TNPs) and cadmium (Cd 2+ ) on rat liver and the potential protective role of coenzyme Q10 (CQ10) against TNPs and Cd 2+ -induced hepatic injury. Seventy male Sprague Dawley rats were divided into seven groups and orally given distilled water, corn oil, CQ10 (10 mg/kg b.wt), TNPs (50 mg/kg b.wt), Cd 2+ (5 mg/kg b.wt), TNPs + Cd 2+ , or TNPs + Cd 2+ +CQ10 by gastric gavage for 60 successive days. The results showed that individual or mutual exposure to TNPs and Cd 2+ significantly increased the serum levels of various hepatic enzymes and lipids, depleted the hepatic content of antioxidant enzymes, and increased malondialdehyde. Moreover, the hepatic titanium and Cd 2+ content were increased considerably in TNPs and/or Cd 2+ -exposed rats. Furthermore, marked histopathological perturbations with increased immunoexpression of tumor necrosis factor-alpha and nuclear factor kappa B were evident in TNPs and/or Cd 2+ -exposed rats. However, CQ10 significantly counteracted the damaging effect of combined exposure of TNPs and Cd 2+ on the liver. The study concluded that TNPs and Cd 2+ exposure harm hepatic function and its architecture, particularly at their mutual exposure, but CQ10 could be a candidate protective agent against TNPs and Cd 2+ hepatotoxic impacts., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background and Objectives: This study aimed to assess the effect of zinc oxide nanoparticles (ZNPs) and/or arsenic trioxide (ATO) exposure on the liver of adult male Sprague Dawley rats. Moreover, the probable ameliorative impact of gallic acid (GA) against ZNPs and ATO-induced hepatotoxicity and the possible underlying mechanisms were evaluated., Methods: Sixty male Sprague Dawley rats were distributed into six groups. The 1 st and 2 nd groups were orally given distilled water (1 ml/kg) and 20 mg GA/kg b. wt, respectively. The 3 rd and 4 th groups were orally given 100 mg ZNPs/kg b. wt and 8 mg ATO/kg b. wt, respectively. The 5 th group was co-administered ZNPs and ATO at the doses mentioned above. The last one was co-administered ZNPs, ATO, and GA at the earlier described doses. All tested compounds were orally given once a day for 60 successive days. Then, serum levels of alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), total, direct, indirect bilirubin, triglycerides, total cholesterol, HDL, VLDL, and LDL were estimated. The hepatic content of malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GPx) was evaluated. Moreover, Bcl-2 and Bax's reactive proteins were immunohistochemically detected, and Zn and As residual patterns in hepatic tissues were assessed., Results: ZNPs, ATO, and ZNPs+ATO-exposed rats showed significantly ( P  < 0.001) elevated serum AST (219%, 233%, and 333%), ALT (300%, 400%, and 475%), ALP (169%, 205%, and 294%), and total bilirubin (42%, 68%, and 109%) compared to the control ones. On the other hand, a significantly ( P  < 0.001) declined SOD (58%, 49%, and 43%) and GPx (70%, 63%, and 56%) but increased MDA (133%, 150%, and 224%) was recorded in the hepatic tissues of ZNPs, ATO, and ZNPs+ATO exposed rats, respectively, relative to the control rats. Moreover, the hepatic tissues of the ZNPs, ATO, and ZNPs+ATO exposed rats showed a significant ( P  < 0.001) decrease in Bcl-2 (28%, 33%, and 23%) but elevation in Bax (217%, 267%, and 236%) immunoreactivities compared to the control rats. These findings were consistent with the microscopic alterations in the hepatic architecture and accumulation of Zn and As. Furthermore, a notable hyperlipidemic condition was recorded following ZNPs and/or ATO exposure. On the contrary, GA notably reduced hepatic enzymes compared to ZNPs+ATO-exposed rats. Additionally, GA markedly improved ZNPs+ATO-afforded liver tissue damage and apoptotic events., Conclusion: Overall, GA oral dosing significantly mitigated the negative effects of ZNPs and ATO on the liver by improving the antioxidant defense system and controlling apoptotic changes., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Chemical food preservatives are extensively found in various processed food products in the human environment. Hence, this study aimed to investigate the effect of long-term exposure to five food preservatives (potassium sorbate (PS), butylated hydroxyanisole (BHA), sodium benzoate (SB), calcium propionate (CP), and boric acid (BA)) on the liver and kidney in rats and the probable underlying mechanisms. For 90 days, sixty male albino rats were orally given either water (control), 0.09 mg/kg b.wt BHA, 4.5 mg/kg b.wt PS, 0.9 mg/kg b.wt SB, 0.16 mg/kg b.wt BA, or 0.18 mg/kg b.wt CP. Liver and kidney function tests were assessed. Hepatic and renal oxidative stress biomarkers were estimated. Histologic examination analysis of liver and kidney tissues was achieved. Toll-like receptors 2 and 4 (TLR-2 and TLR-4), tumor necrosis factor-alpha (TNF-α), and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) mRNA expression levels were measured. The results revealed that long-term oral dosing of the five food preservatives resulted in significant increases in alkaline phosphatase, alanine transaminase, aspartate transaminase, urea, uric acid, and creatinine levels. There were significant reductions in hepatic and renal antioxidant enzymes, an increase in MDA concentrations, and pathological alterations in renal and hepatic tissues. The mRNA levels of TLR-4, TLR-2, NF-κB, and TNF-α were elevated in the food preservatives-exposed groups. Conclusively, the current findings revealed that long-term exposure to PS, BHA, SB, CP, and BA has a negative impact on liver and kidney function. Furthermore, these negative effects could be mediated via oxidative stress induction, inflammatory reactions, and cytokine production., (© 2023. The Author(s).)

The present study was designed to evaluate the probable ameliorative role of quercetin (QCN) against oxidative hepatotoxicity induced by aluminum oxide nanoparticles (Al 2 O 3 NPs) with a diameter < 30 nm and lead acetate (Pb) co-exposure in adult male Sprague-Dawley rats. Rats were weighed and allocated to seven groups (n = 10 each) and were treated orally via orogastric gavage for 60 successive days: rats of the 1st group were kept as control given distilled water (1 ml/kg), rats of the 2nd group received 2 ml/kg BW/day corn oil; rats of the 3rd group were administered 20 mg/kg BW QCN/day; rats of the 4th group received 100 mg/kg BW Al 2 O 3 NPs; rats of the 5th group received 50 mg/kg BW Pb; rats of the 6th group co-received Al 2 O 3 NPs and Pb at the same previous doses; and rats of the 7th group were co-administered Al 2 O 3 NPs, Pb, and QCN at the same previous doses. At the end of the experiment, serum levels of alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), total, direct, indirect bilirubin, triglycerides, total cholesterol, HDL, VLDL, and LDL were estimated. The hepatic oxidative stress biomarkers as superoxide dismutase (SOD), malondialdehyde (MDA), and glutathione peroxidase (GPx), were also evaluated. Finally, the histopathological and histomorphometric evaluations and the residues of Al and Pb in hepatic tissues were assessed. Al 2 O 3 NPs and/or Pb exposure significantly elevated lipid peroxidation levels and considerably altered the hepatic biochemical parameters; nevertheless, QCN significantly reduced hepatic enzymes compared to toxicant exposed groups. Additionally, QCN significantly improved Al 2 O 3 NPs-afforded liver tissue damage, as established in microscopic findings on the liver in the group treated with Al 2 O 3 NPs + Pb. Conclusively, QCN could be a candidate natural agent to safeguard the liver versus the co-harmful impacts of Al 2 O 3 NPs and Pb toxicity., (© 2022. The Author(s).)

This study examined the effects of exposure to lead acetate (PbAc) and/or aluminum trioxide nanoparticles (Al 2 O 3 NPs) on testicular function. Additionally, the probable reproprotective effects of quercetin (QTN) against Al 2 O 3 NPs and PbAc co-exposure in male Sprague Dawely rats were assessed. Al 2 O 3 NPs (100 mg/kg b.wt.), PbAc (50 mg/kg b.wt.), and QTN (20 mg/kg b.wt.) were orally administered for 60 days. Then, spermiogram, histopathological examinations of the testis and accessory glands, and immunohistochemical detection of androgen receptors (AR) and tumor necrotic factor alpha (TNF-α) were achieved. Moreover, serum levels of male sex hormones and testicular levels of antioxidant indices were estimated. The results showed that Al 2 O 3 NP s and/or PbAc caused significant sperm abnormalities, testicular oxidative stress, and histopathological changes. Furthermore, serum testosterone, LH, and FSH levels significantly decreased, while estradiol levels significantly increased. The Al 2 O 3 NPs and/or PbAc co-exposed group had more obvious disturbances. Furthermore, QTN co-administration significantly reversed the Al 2 O 3 NPs and PbAc-induced testicular histopathological alterations, reduced antioxidant defenses, and altered AR and TNF-α immune expression in testicular tissues. Conclusively, Al 2 O 3 NPs and/or PbAc evoked testicular dysfunction by inducing oxidative injury and inflammation. However, QTN oral dosing effectively mitigated the negative effects of Al 2 O 3 NPs and PbAc by suppressing oxidative stress and inflammation and improving the antioxidant defense system.

Oxidative stress resulting from the disproportion of oxidants and antioxidants contributes to both physiological and pathological conditions in sepsis. To combat this, the antioxidant defense system comes into the picture, which contributes to limiting the amount of reactive oxygen species (ROS) leading to the reduction of oxidative stress. However, a strong relationship has been found between scavengers of ROS and antioxidants in preclinical in vitro and in vivo models. ROS is widely believed to cause human pathology most specifically in sepsis, where a small increase in ROS levels activates signaling pathways to initiate biological processes. An inclusive understanding of the effects of ROS scavenging in cellular antioxidant signaling is essentially lacking in sepsis. This review compiles the mechanisms of ROS scavenging as well as oxidative damage in sepsis, as well as antioxidants as a potent therapeutic. Direct interaction between ROS and cellular pathways greatly affects sepsis, but such interaction does not provide the explanation behind diverse biological outcomes. Animal models of sepsis and a number of clinical trials with septic patients exploring the efficiency of antioxidants in sepsis are reviewed. In line with this, both enzymatic and non-enzymatic antioxidants were effective, and results from recent studies are promising. The usage of these potent antioxidants in sepsis patients would greatly impact the field of medicine.

There is a global increase in daily dietary intake of acrylamide (ACR) owing to its presence in various foods. However, several toxicological issues are still unclear, particularly after oral exposure to low doses for long durations. As a result, the objective of this research was to investigate the effects of giving male Wistar rats two dosages of ACR (1 or 2 mg/kg b.wt.) via oral gavage once a day for 90 days on blood components, immune markers, and splenic tissue. The results revealed that leukopenia, lymphocytopenia, eosinophilia, and thrombocytopenia were all found to be ACR dose-dependent. In addition, ACR-treated rats had considerably higher IgG and IgM levels. Following ACR exposure, phagocytic activity, lysozyme, and nitric oxide levels were significantly reduced. In ACR-exposed rats, there was a significant reduction in lymphocyte proliferation but an increase in LDH activity. Both splenic tissue and bone marrow showed a variety of degenerative changes. There was a significant increase in CD4 + and CD8 + immunolabeling. Rats exposed to ACR at both levels showed a significant rise in comet variables. Overall, our findings suggested that long-term exposure to ACR could cause hematological disorders, DNA damage, and disturbances of immune functions., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Wide nanotechnology applications and the commercialization of consumer products containing engineered nanomaterials (ENMs) have increased the release of nanoparticles (NPs) to the environment. Titanium dioxide, aluminum oxide, zinc oxide, and silica NPs are widely implicated NPs in industrial, medicinal, and food products. Different types of pollutants usually co-exist in the environment. Heavy metals (HMs) are widely distributed pollutants that could potentially co-occur with NPs in the environment. Similar to what occurs with NPs, HMs accumulation in the environment results from anthropogenic activities, in addition to some natural sources. These pollutants remain in the environment for long periods and have an impact on several organisms through different routes of exposure in soil, water, and air. The impact on complex systems results from the interactions between NPs and HMs and the organisms. This review describes the outcomes of simultaneous exposure to the most commonly found ENMs and HMs, particularly on soil and aquatic organisms.

The food additives thiabendazole (TBZ), monosodium glutamate (MSG), and brilliant blue (BB) are commonly used in many daily-consumed food products worldwide. They are widely used in major agricultural and industrial applications. Yet, many of its toxicological aspects are still unclear, especially immune modulation. This research was therefore intended to investigate the effects of male Wistar rats' daily oral exposure for 90 days to TBZ (10 mg/kg b.wt), MSG (20 mg/kg b.wt), or BB (1.2 mg/kg b.wt) on the blood cells, immunity, and inflammatory indicators. The three tested food additives showed varying degrees of hematological alterations. Initially, megaloblastic anemia and thrombocytopenia were evident with the three tested food additives. At the same time, TBZ showed no significant changes in the leukogram element except eosinopenia. MSG induced leukopenia, lymphocytopenia, neutrophilia, and eosinophilia. BB evoked neutrophilia and lymphopenia. The immunoglobins M (IgM) and IgG were significantly reduced with the three tested food additives. In contrast, lysozyme and nitric oxide levels were elevated. A reduced considerably lymphocyte proliferation was detected with TBZ and MSG exposure without affecting the phagocytic activity. Various pathologic disturbances in splenic tissues have been detected. An obvious increase in CD4 + but a lessening in CD8 + immunolabeling was evident in TBZ and MSG groups. The cytokines, including interferon-gamma, tumor necrosis factor-alpha, and interleukin 1β, 6, 10, and 13, were significantly upregulated in the spleen of rats exposed to TBZ, MSG, and BB. These results concluded that TBZ, MSG, and BB negatively affect hematological parameters, innate and humoral immune functions together with inflammatory responses. TBZ achieved the maximal negative impacts followed by MSG and finally with BB. Given the prevalence of these food additives, TBZ and MSG should be limited to a minimal volume use, or natural food additives should be used instead., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Fresh stem cell exosomes are usually obtained and reused in the same individual. It cannot be kept viable for a long period of time regardless of the lengthy preparation time. Freezing is typically used to preserve the viability of perishable materials and increase their lifetime. Regrettably, normal freezing of biomaterials leads to cell damage. Therefore, a cryoprotectant can save the cells from the conventional cryodamage. Sodium carboxymethylcellulose (NA-CMC) is a powdery substance that is used to manufacture bio-safe hydrofilm gels because of its high viscosity, cytocompatibility, and nonallergenic nature. Materials and Methods:  Sterile CMC hydrogel was prepared, part of which was loaded with exosomal solution derived from MSCs. The gel was kept at -20°C for preservation. Two bilateral full-thickness circular skin wounds of 2-cm diameter were created on the back of experimental dogs. The wounds were at least 2.5 cm apart. Treatment started 24 hours after wound creation. Group I received CMC gel solely, whereas group II received frozen CMC exosomal gel. The gel was applied 4 times, a single application per day with 1- day interval. Results: Clinically, the frozen exosomal gel significantly promoted wound healing with no scaring. Histologically, enhanced dermal fibroblasts and organized collagen deposition were seen in the treated group. Conclusion: CMC proved to be an efficient cryoprotectant and a suitable vehicle for exosomes. Deep freezing was proven to conserve the viability, extended the preservation, and facilitated the usage of exosomal gel. This technique of preserved cell-free therapy is inexpensive, time-saving, and proficient and seems suitable for treating cutaneous wounds., (Copyright © 2021 Tehran University of Medical Sciences.)

The pharmacokinetics of marbofloxacin (MAR) was compared in geese (Anser Anser domesticus) after single intravenous (IV) and intramuscular (IM) (thigh and pectoral muscles) administrations of 5 mg/kg. Serum concentrations of MAR were determined with high-performance liquid chromatography (HPLC) method. Serum MAR concentrations versus time were analyzed by a noncompartmental method. After IV administration, MAR showed high volume of distribution at steady state (V dss ) of 5.24 ± 1.08 L/kg. The serum body clearance (Cl) and elimination half-life (T 1/2 λz) of MAR were 0.79 ± 0.07 L hr -1  kg -1 and 6.94 ± 1.12 hr, respectively. The peak of MAR serum concentrations C max achieved at one and 0.50 hr after thigh and pectoral IM sites of injections, respectively, were 1.20 and 0.91 μg/ml. Significant differences were found in the mean absorption time (MAT), the systemic bioavailability (F%), and elimination parameters of MAR between two sites of injections, indicating that the absorption was fairly slow and complete after thigh IM injection. The pharmacokinetics of MAR in geese diverged according to the site of IM injection following a parallel study design. We recommend the thigh muscle as IM site of injection to obtain maximum concentrations of the administered drug in geese., (© 2020 John Wiley & Sons Ltd.)

Background: Titanium dioxide "TiO 2 , E171″ is a widely used food additive that exists in various everyday food products all over the world together with vast applications in cosmetics and industry. However, many toxicological aspects particularly following oral exposure still unclear., Methods: Hence, this study was planned to examine the effect of oral exposure of male Wistar rats to two doses of TiO 2 (20 or 40 mg/kg b.wt.) through oral gavage once daily for 90 consecutive days on the blood components, immunity, cytotoxic, and genotoxic indicators., Results: A dose-dependent leukopenia, eosinophilia, neutrophilia, and thrombocytopenia were noted. Also, the immunoglobins G (IgG) and IgM were significantly elevated in TiO 2 treated rats. The phagocytic activities, lysozyme, nitric oxide, and immunoglobulin levels were significantly depleted following TiO 2 exposure. A significantly reduced lymphocyte proliferation but elevated LDH activity was prominent in TiO 2 treated rats. Different pathological perturbations were observed in both splenic tissue and bone marrow. A marked increase in CD4 + and CD8 + immunolabeling was evident. A significant increase in the comet variables was recorded in response to the exposure of rats to the increasing level of TiO 2 at both levels., Conclusion: Overall, these results indicated that TiO 2 could induce hematotoxicity, genotoxic, and immunotoxic alterations with exposure for long durations., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2020 Elsevier GmbH. All rights reserved.)

Background/aims: Food preservatives are abundant in many products in the human environment. However, little is known about the impact of many food preservatives on the immune system and the immune related genes. Hence, this study aimed to evaluate the effects of five widespread food preservatives, including butylated hydroxyanisole (BHA), potassium sorbate (PS), sodium benzoate (SB), boric acid (BA), and calcium propionate (CP), on haemato-immune functions., Method: Sixty Sprague-Dawley rats were assigned to groups orally administered water (control), BHA (0.09 mg/kg), PS (4.5 mg/kg), SB (0.9 mg/kg), BA (0.16 mg/kg) or CP (0.18 mg/kg) for 90 consecutive days. Leukogram and erythrogram profiles were assessed. Nitric oxide and immunoglobulin levels together with phagocytic and lysozyme activities were estimated. Histologic examinations and histomorphometric analysis of splenic tissues were performed. Variations in the mRNA expression levels of tumour necrosis factor alpha (TNF-α), interferon gamma (IFNγ), interleukin (IL)-1β, IL-6, and IL-10 were assessed., Results: Anemic conditions, thrombocytopenia, leucocytopaenia simultaneous with lymphocytopaenia, monocytopenia, and esinopenia have been obvious following long term exposure to the tested food additives. Prominent exhaustion was noted in immunoglobulin and NO levels and in lysozyme and phagocytic activities. IFNγ, TNF-α, IL-1β, IL-6, and IL-10 were obviously upregulated in the groups exposed to food preservatives., Conclusion: These results confirmed that continued exposure to high levels of BHA, PS, SB, BA, and CP has haematotoxic and immunotoxic effects. Furthermore, these adverse effects are mediated by cytokine production., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Extracellular vesicles (EVs) are nanosized vesicles released by different cells and have been separated from most of the body fluids. These vesicles play a central role in cell-to-cell communications as carry a distinct cargo including proteins, RNA species, DNAs, and lipids that are meant to be shipped and exchanged between cells at both systemic and paracrine levels. They serve in regulating normal physiological processes. EVs released from stem cells exert similar therapeutic effect to their originating cells. Clinical application of EVs requires the preparation of sufficient and viable active therapeutic EVs as well as implementing suitable methods for long-term preservation to expedite both their clinical and commercial uses. Cryopreservation is the most common method used to preserve decomposable biomaterials. However, cryopreservation causes cryoinjury to cells which therefore necessitate the use of cryoprotectants. Two types of cryoprotectants exist: penetrating and non-penetrating. In freeze drying, the watery content is sublimed from the product after it is frozen. This drying process is pertinent to thermo-liable substances and those unstable in aqueous solutions for prolonged storage periods. In spray drying technique, the solution containing EVs is firstly atomized, then droplets are rapidly converted into a dry powder using heated gas. Even with the exposure to high temperatures of the drying gas, spray drying is considered suitable for heat-sensitive materials. EVs are considered a promising cell-free therapy, but the lack of proper preservation limits its benefits. Preservation of EVs will initiate a vast amount of clinical trials on different species and different clinical problems., (© 2019 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Colouring agents are highly present in diverse products in the human environment. We aimed to elucidate the fibrogenic cascade triggered by the food dyes tartrazine and chlorophyll. Rats were orally given distilled water, tenfold of the acceptable daily intake of tartrazine, or chlorophyll for 90 consecutive days. Tartrazine-treated rats displayed a significant rise (p < 0.05) in the mRNA levels and immunohistochemical localization of the renal and hepatic fibrotic markers collagen 1-α, TGFβ-1, and fibronectin and the apoptotic marker caspase-3. Moreover, a significant increment (p < 0.05) in the levels of AST, ALP, creatinine, and urea was evident in both experimental groups but more significant differences were noticed in the tartrazine group. Furthermore, we found a marked increment in the MDA level and significant declines (p < 0.05) in the levels of the SOD, CAT, and GSH enzymes in the kidney and liver from tartrazine-treated rats. The histological investigation reinforced the aforementioned data, revealing hepatocytes with fibrous connective tissue proliferation, apoptotic hepatocytes and periportal fibrosis with tubular necrosis, and shrunken glomeruli and interstitial fibrous tissue proliferation. We concluded that, even at the exposure to high concentrations for long durations, chlorophyll exhibited a lower propensity to induce fibrosis, apoptosis, and histopathological perturbations than tartrazine.

Tartrazine (TAZ) is one of the most commonly used artificial dyes for foods and drugs. We determined the effect of TAZ on fetal development by examining morphological, visceral, and skeletal malformations in rat fetuses following daily oral administration of TAZ to pregnant Wistar rats at the 6th-15th day of gestation. TAZ at 0.45 and 4.5 mg/kg induced 6.0 and 7.1% fetal resorptions, as well as 10.0 and 10.5% fetal mortality, respectively. Fetal body weight and length were significantly lower in the groups treated with TAZ at 0.45 (3.97 ± 0.21 g and 27.3 ± 0.54 mm, respectively) and 4.5 mg/kg (3.48 ± 0.15 g and 23.22 ± 1.02 mm, respectively) than in the control group (4.0 ± 0.15 g and 30.01 ± 0.42 mm, respectively). TAZ at 0.45 and 4.5 mg/kg induced hepatic damage (20 and 33.3%, respectively), dark brown pigmentation due to hemosiderin in the splenic parenchyma (16.7 and 21.7%, respectively), as well as destructed and necrotic renal tubules (16.7 and 26.7%, respectively) in the fetuses. Moreover, TAZ at 0.45 and 4.5 mg/kg caused one or more missing coccygeal vertebrae (20 and 40%, respectively), missing sternebrae (6 and 10%, respectively), missing hind limbs (24 and 4%, respectively), and irregular ribs (16 and 20, respectively) in the fetuses. We concluded that TAZ has embryotoxic and teratogenic potentials in rats., Competing Interests: CONFLICT OF INTEREST The authors declare no conflict of interest.

The haemato-immunotoxic effects of the food colourants tartrazine and chlorophyll were evaluated. Thirty adult Sprague Dawley rats were distributed into three groups and orally administered water, tartrazine (1.35 mg/kg), or chlorophyll (1.35 mg/kg) daily for 90 days. Erythrogram and leukogram profiles were evaluated. The lysozyme, nitric oxide, phagocytic activity, and immunoglobulin levels were measured. Histological and immunohistochemical evaluations of splenic tissues were conducted. Changes in the interleukin (IL) 1β, 6, and 10 mRNA expression levels were assessed. In the tartrazine-treated rats, a significant anaemic condition and marked leukocytosis were observed. Both the innate and humoural parameters were significantly depressed. Different pathological lesions were observed, including red pulp haemorrhages, vacuolation of some splenic cells, focal hyperplasia of the white pulp, and capsular and parenchymal fibrosis. A marked increase in vascular endothelial growth factor (VEGF) and endothelial nitric oxide synthase (e-NOS) immunolabelling was evident. Marked upregulation of IL-1β, IL-6, and IL-10 was recorded. In contrast, the chlorophyll-treated rats showed minimal haemato-immune responses. These results indicate that tartrazine exerts haematotoxic and immunotoxic effects following long-term exposure, whereas chlorophyll is a less hazardous food colourant., (Copyright © 2018 Elsevier B.V. All rights reserved.)

The present study assessed the long-term daily administration of benzoic acid (BA), potassium sorbate (PS), chlorophyll (CPL), tartrazine (TAZ), and butylated hydroxyanisole (BHA) on hepato-renal changes and DNA damage in rats. Animals were orally administered with the 10 times of the acceptable daily intake (ADI) from each tested substance daily for 60 consecutive days. Blood, liver, and kidney samples were collected to evaluate hematological, biochemical, histopathological, and genotoxic alterations. The extent of liver and kidney damage was evaluated by comet assay and histopathologically. Significant reduction of leukocyte numbers and lymphocytes % in CPL- and TAZ-treated rats. However, significant increases in platelet count in all treated groups after 60 days were detected. The levels of serum transaminases enzymes (ALT, AST), alkaline phosphatase (ALP), and creatinine were significantly increased in all treatments except with BHA group, but no substantial differences were found in urea after 60 days. Aside from BHA, results of DNA damage revealed significant increases in tailed nuclei, tail moment, DNA% in the tail, and tail length in liver and kidney at different degrees. Moreover, the histopathological figures of liver and kidneys affirmed destructive and degenerative changes. The study indicates that most of the tested food additives may provoke genotoxicity and hepato-nephropathy, which could be serious for human health. Therefore, it is necessary to be informed about the hazardous effects of food additives and more attention should be focused towards using natural substitutes.

The present study was planned to examine the effect of butylated hydroxy toluene (BHT) on the immune response of Rift Valley fever vaccine (RVFV) in Swiss mice. Animals were divided into four equal groups. The first group was kept as negative control. The 2nd group was orally administrated with the acceptable daily intake (ADI) of BHT 0.3 mg/kg b.wt. daily for 21 days and the 3rd group were vaccinated only by inactivated RVFV at a dose of 0.2 ml I/P two times. The 4th group was orally administrated BHT as in the 2nd group and vaccinated by inactivated RVFV as in the 4th group. Blood samples were collected from all groups two weeks from booster vaccination. The cellular immunity was determined by leucocytic indices and the neutrophil-lymphocyte ratio (NLR) whereas, humoral immunity was evaluated with IgG antibodies titer using enzyme-linked immune-sorbent assay (ELISA) test, serum neutralization test (SNT) and challenge test. BHT induced leucopenia, neutrophilia and marked lymphocytopenia in both non-vaccinated and vaccinated mice. Moreover, BHT significantly decreased the efficiency of vaccination by inducing 70% cytopathic effect (CPE) in the infected cell cultures and increasing the ED 50 value of RVFV vaccine. The present study indicates that BHT possesses a potential for decreasing both cellular and humoral mediated mechanisms., (Copyright © 2018 Elsevier B.V. All rights reserved.)

The food additives sodium acid pyrophosphate (SAPP), sodium acetate (SA), and citric acid (CA) were evaluated for their hemato-immunotoxic effects. Forty adult Sprague-Dawley rats were distributed into four groups and were orally administered water, SAPP (12.6 mg/kg), CA (180 mg/kg), or SA (13.5 mg /kg) daily for 90 days. Erythrogram and leukogram profiles were evaluated. The levels of lysozyme, nitric oxide, immunoglobulin, and phagocytic activity were measured. Histologic and immunohistochemical evaluations of splenic tissues were performed. Changes in the mRNA expression levels of peroxisome proliferator-activated receptor α and γ (PPAR-α and PPAR-γ), and tumor necrosis factor α (TNF-α) genes were assessed. A significant leukopenic condition was observed with SAPP, while CA induced marked leukocytosis, and SA showed a lymphocytosis condition. Both the innate and humoral parameters were significantly depressed. Various pathological lesions were observed, including diffuse hyperplasia of the red pulp, depletion of the white pulp, and capsular and parenchymal fibrosis. A marked decrease in CD3 T-lymphocyte and CD20 B-lymphocyte immunolabeling in rats treated with SAPP and SA was evident. Marked downregulation of PPAR-α and PPAR-γ together with upregulation of TNF-α was recorded. These results indicate that high doses of SAPP, SA and CA exert hematotoxic and immunotoxic effects with long-term exposure., (Copyright © 2018 Elsevier B.V. All rights reserved.)

The present study examined the impacts of sodium acetate (SA), sodium acid pyrophosphate (SAPP), and citric acid (CA) on the viability, proliferation, and DNA damage of isolated lymphocytes in vitro. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and lactate dehydrogenase (LDH) release assays were adopted to evaluate cell viability, while comet assay was employed to assess the genotoxic effects. The cells were incubated with different levels of SA (50, 100, and 200 mM), SAPP (25, 50, and 100 mM/L), or CA (100, 200, and 300 μg/mL). The lymphocytes treated with the tested food additives showed concentration-dependent decreases in both cell viability and proliferation. A concentration-dependent increase in LDH release was also observed. The comet assay results indicated that SA, SAPP, and CA increased DNA damage percentage, tail DNA percentage, tail length, and tail moment in a concentration-dependent manner. The current results showed that SA, SAPP, and CA are cytotoxic and genotoxic to isolated lymphocytes in vitro., (© 2018 Wiley Periodicals, Inc.)

In this review, we have discussed the recent potential effects of plants and their derivatives in treating diseases of veterinary importance in livestock. The therapeutic value of these natural products depends upon their bioactive metabolites that are developed and isolated from crude plants, thus produced a selective action on the body. The crises of drug resistance in most pathogenic bacteria and parasites that cause economic loss in animals necessitate developing new sources for drugs to overcome therapeutic failure. We summarized the different antibacterial and antiparasitic plants with their bioactive compounds that have widely used in animals. Finally, the environmental friendly feed additives that may be used as alternatives to an antibiotic growth promoter for broiler chickens were illustrated.