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The hilly and rural areas’ people of Bangladesh have a great history of putting into use numerous traditional medicinal plants to cure diseases. Therefore, with ethanol extract of Molineria capitulata (EEMC), methanol extract of Trichosanthes tricuspidata (METT), and methanol extract of Amorphophallus campanulatus (MEAC), we mandate evaluation of in vitro α-amylase inhibition, antioxidants, and molecular docking, and ADMET/T analysis. According to iodine starch methods, α-amylase inhibition was performed, and quantitative total phenolic and flavonoid content was determined by established methods, whereas DPPH free radical scavenging and reducing power assays were performed in previously established protocols, respectively. A comparative study among three plants (EEMC, METT, and MEAC) possessed a significant ( p < 0.01 ) effect but EEMC showed the highest impact on enzyme inhibition. Plants in the measuring phenolic content METT and flavonoid measurement MEAC displayed most potent in the same way in the DPPH test was METT, and in reducing power capability MEAC has showed the highest effect between three extracts. Docking’s study also reveals the compounds of METT (Cyclotricuspidoside A and Cyclotricuspidoside C) exhibit the superior score among all the compounds. This finding indicates that EEMC, METT, and MEAC substantially impact α-amylase inhibition along with antioxidants. In silico study also reveals the potency of these plants, but further in-depth, precise molecular studies are needed.

The edible herb Sterculia foetida L. has potential nutraceutical and medicinal effects. The present study is performed to assess the possible antidiabetic, neuropharmacological, and antidiarrheal activity of the methanolic extract of S. foetida seeds (MESF) through in vitro, in vivo, and in silico approaches. When compared to standard acarbose, the results of the antidiabetic study provided strong proof that the glucose level in the MESF was gradually decreased by inhibiting the function of α-amylase enzymes. The sedative potential of MESF (200 and 400 mg/kg) was determined by employing open field, hole cross, and thiopental sodium-induced sleeping time tests, which revealed significant reductions in locomotor performance and increased sleep duration following MESF treatment. In addition, mice treated with MESF exhibited superior exploration during elevated plus maze and hole board tests. MESF also showed good antidiarrheal activity in castor oil-induced diarrhea and intestinal motility tests. Previously isolated compounds (captan, 1-azuleneethanol, acetate, and tetraconazole) exhibited good binding affinity in docking studies and drug-likeliness properties in absorption, distribution, metabolism, excretion/toxicity (ADME/T), and toxicological studies. Collectively, these results indicate the bioactivity of S. foetida, which represents a potential candidate in the food and pharmaceutical industries.

The present study examines the neuropharmacological and antidiabetic properties of methanol leaves extract of Lannea coromandelica in animal models. This study is carried out by elevated plus-maze apparatus, motor coordination, thiopental sodium has an induction role in sleeping time, hole board, hole cross, open field, antidiabetic studies. Mice were treated doses of 100, 150, and 200 mg/kg body weight in elevated plus-maze apparatus and motor coordination; 100 and 200 mg/kg body weight in sleeping time, hole cross, hole board, and open field tests; and 200 and 400 mg/kg body weight in the antidiabetic activity test. Extraction specifies a significantly decreased time duration and sleeping time in a thiopental sodium-induced sleeping time test. The experimental extract decreased locomotor and exploratory behaviors of mice in the open-field and hole-cross tests compared to the effects of the control. Furthermore, the extract increased sleeping time with a dose-dependent onset of action. The hole-board test extract also demonstrated a reduced number of head dips. The findings showed that L. coromandelica has potential neuropharmacological effects. In addition, in alloxan-induced diabetic mice, leaves extract at 200 and 400 mg/kg body weight revealed significant antidiabetic properties and could be used to manage blood glucose levels with more research.

Ginkgo biloba is an ancient plant species that is thought to provide a variety of health benefits to living organisms and contains plenty of bioactive components, making it a chemically diversified plant. G. biloba has been shown to have a variety of medicinal and pharmacological properties, including anticancer, antidementia, antidiabetic, antiobesity, antilipidemic, antimicrobial, antioxidant, antilipid peroxidation, antiplatelet, anti-inflammatory, hepatoprotective, antidepressant, antiaging, immunomodulatory, antihypertensive, and neuroprotective effects and is frequently used to treat neurological, cardiovascular, and respiratory diseases, such as tardive dyskinesia. Therefore, this review described the therapeutic applications of G. biloba. In addition to describing the therapeutic potential, this review also evaluates the chemical constituents, toxicity, adverse effect, synergistic effect, and the clinical studies of this plant which have been utilized for therapeutic benefits but have demonstrated other consequences. The capacity of G. biloba components to act as free radical scavengers is critical, and combining its extract with other plant extracts has been shown to synergistically boost antioxidant properties. G. biloba used long-term or at high doses that resulted in some adverse effects. Severe drug interactions have also been reported in both animals and humans when combined with other medications. The available data established from both preclinical and clinical studies confirm the potential of G. biloba plant extract in various diseases. Besides, the safety and efficacy of G. biloba continue to require verification through additional experimentation to guide medicinal use.

The oxadiazole ring has long been used for the treatment of several diseases. This study aimed to analyze the antihyperglycemic and antioxidant roles of the 1,3,4-oxadiazole derivative with its toxicity. Diabetes was induced through intraperitoneal administration of alloxan monohydrate at 150 mg/kg in rats. Glimepiride and acarbose were used as standards. Rats were divided into groups of normal control, disease control, standard, and diabetic rats (treated with 5, 10, and 15 mg/kg of 1,3,4-oxadiazole derivative). After 14 days of oral administration of 1,3,4-oxadiazole derivatives (5, 10, and 15 mg/kg) to the diabetic group, the blood glucose level, body weight, glycated hemoglobin (HbA1c), insulin level, antioxidant effect, and histopathology of the pancreas were performed. The toxicity was measured by estimating liver enzyme, renal function, lipid profile, antioxidative effect, and liver and kidney histopathological study. The blood glucose and body weight were measured before and after treatment. Alloxan significantly increased blood glucose levels, HbA1c, alanine transaminase, aspartate aminotransferase, urea, cholesterol, triglycerides, and creatinine. In contrast, body weight, insulin level, and antioxidant factors were reduced compared to the normal control group. Treatment with oxadiazole derivatives showed a significant reduction in blood glucose levels, HbA1c, alanine transaminase, aspartate aminotransferase, urea, cholesterol, triglycerides, and creatinine as compared to the disease control group. The 1,3,4-oxadiazole derivative significantly improved body weight, insulin level, and antioxidant factors compared to the disease control group. In conclusion, the oxadiazole derivative showed potential antidiabetic activity and indicated its potential as a therapeutic.

Repeated acrylamide (ACR) exposure in experimental animals and humans causes variable degrees of neuronal damage. Because of its unique features, several green synthesized nanomaterials are explored for neuromodulatory activity. Hence, this study investigated the effect of green synthesized zinc oxide nanoparticles using Moriga olifera leaves extract (MO-ZnONP) against acrylamide (ACR)-induced neurobehavioral and neurotoxic impacts in rat. Forty male Sprague Dawley rats were distributed into four groups orally given distilled water, MO-ZnONP (10 mg/kg b.wt), ACR (20 mg/kg b.wt), or MO-ZnONP + ACR for 60 days. Gait quality and muscular, motor, and sensory function were assessed. Acetylcholinesterase (AChE), dopamine, catalase, malondialdehyde (MDA), and Zn brain contents were determined. Brain histopathology and immunohistochemical localization of the amyloid-β protein and abnormal Tau were performed. The results revealed that MO-ZnONP significantly reduced ACR-induced sensory dysfunctions, hind limb abnormality, and motor deficits. Additionally, the ACR-induced increase in dopamine and AChE were significantly supressed by MO-ZnONP. Besides, MO-ZnONP significantly restored catalase and Zn content but reduced increased MDA brain content resulting from ACR. Furthermore, the ACR-induced neurodegenerative changes and increased amyloid-β and phosphorylated Tau immunoexpression was significantly abolished by MO-ZnONP. Conclusively, MO-ZnONP could be used as a biologically effective compound for mitigating ACR's neurotoxic and neurobehavioral effects.

© 2021 by the authors. Licensee MDPI, Basel, Switzerland.In many countries, the fruit of betel (Piper betle Linn) is traditionally used as medicine for treating malaria. It is a fatal disease, and existing medications are rapidly losing potency, necessitating the development of innovative pharmaceutics. The current study attempted to determine the compounds in the n-hexane fraction of betel fruit extract and investigate the potential inhibition of bioactive compounds against aspartic protease plasmepsin 1 (PDB ID: 3QS1) and plasmepsin 2 (PDB ID: 1LEE) of Plasmodium falciparum using a computational approach. The ethanol extract was fractionated into n-hexane and further analyzed using gas chromatography-mass spectrometry (GC-MS) to obtain information regarding the compounds contained in betel fruit. Each compound’s potential antimalarial activity was evaluated using AutoDock Vina and compared to artemisinin, an antimalarial drug. Molecular dynamics simulations (MDSs) were performed to evaluate the stability of the interaction between the ligand and receptors. Results detected 20 probable compounds in the n-hexane extract of betel fruit based on GC-MS analysis. The docking study revealed that androstan-17-one,3-ethyl-3-hydroxy-, (5 alpha)-has the highest binding affinity for plasmepsin 1 and plasmepsin 2. The compound exhibits a similar interaction with artemisinin at the active site of the receptors. The compound does not violate Lipinski’s rules of five. It belongs to class 5 toxicity with an LD50 of 3000 mg/kg. MDS results showed stable interactions between the compound and the receptors. Our study concluded that androstan-17-one,3-ethyl-3-hydroxy-, (5 alpha)-from betel fruit has the potential to be further investigated as a potential inhibitor of the aspartic protease plasmepsin 1 and plasmepsin 2 of Plasmodium falciparum.

The skin wound age determination in living subjects is an imperative task for forensic experts. In this study, we investigated the time-dependent expression of high-mobility group box-1 (HMGB1) and toll-like receptors 2 and 4 (TLR2 and 4) in rat skin wounds using real-time PCR and seek their forensic potentials during the skin wound repair process. In addition, the levels of serum pro-inflammatory cytokines (tumor necrosis factor-alpha (TNF-α) and interleukin 6 (IL-6)), as well as nitric oxide (NO) production, were measured. The wound tissue and serum samples were collected after 30 min, 2 h, 6 h, 12 h, 1 day, 3 days, 5 days, and 7 days after incision. As a control (zero time), skin specimens and blood samples were collected without incision. The results reveal that the HMGB1, TLR2, and TLR4 expression levels were increased in a time-dependent manner until the first day where the peak level was achieved for the three tested genes compared with the zero time. On the 7th day, the statistical significance was lost for TLR2 and TLR4 but persisted for HMGB1. The serum TNF-α, IL6, and NO levels peaked within 30 min and 1st and 3rd day after injury, respectively. On the 7th day after incision, no significant differences exist in the TNF-α serum level compared to the control group, but the statistical significance persisted for IL6 and NO. It was apparent that the analyzed genes in the wound tissues showed higher R2 values rather than the serum biochemical indicators. Of note, a strong positive correlation was evident between the HMGB1 and that of TLR2 and TLR4 relative expression as well as IL-6 serum level. Conclusively, based on the observed changes in the analyzed markers in wound tissues and serum and R2 values obtained from mathematical models established to determine the wound age, the relative expression of HMGB1, TLR2, and TLR4 could be a reliable indicator for wound age determination in living subjects. Further investigation of these markers and mathematical models in human tissues is necessary.

The existing study was designed to inspect the toxicological consequences of two pesticides; lambda-cyhalothrin (LCT) and methomyl (MTM) and their combination on Nile tilapia (Oreochromis niloticus) behaviors, oxidative stress, hepato-renal function indices and microarchitectural alterations. In addition, the efficiency of taurine (TUR) to rescue their toxicity was also considered. Juvenile O. niloticus were assigned into eight groups. The control and TUR groups were fed on a basal diet and TUR-enriched (10 g kg

Nicotine is one of several physiologically stable and active chemicals found in tobacco. The mechanism through which nicotine causes kidney damage is still obscure. As a result, the goal of this research was to investigate how oral nicotine intake can lead to kidney damage. Naturaly occurring superfood green algae are immense supplements help us using extra chemicals during cancer prevalence if the patient is exposed to nicotine. Hence, the mitigating role of Chlorella vulgaris extract (CVE) against nicotine-nephrotoxic impact in Ehrlich ascites carcinoma (EAC)-bearing mice was studied. For this purpose, four groups of Swiss female mice were assigned, nicotine group (NIC) (100 µg/ml/kg), CVE group (100 mg/kg), CVE + Nicotine, and a control group. Renal dysfunction was evaluated by estimating serum biomarkers ofrenal damage. The expression pattern of Nf

Indiscriminate use of insecticides is a major concern due to its ubiquitous occurrence and potential toxicity to aquatic animals. This study investigated the adverse effects of lambda-cyhalothrin (LCT, C23H19ClF3NO3) and methomyl (MTM, C5H10N2O2S) on immune system modulations and growth performance of juvenile fishes. The supportive role of a taurine (TUR, C2H7NO3S)-supplemented diet was also evaluated. Juvenile O. niloticus fishes were exposed to LCT (0.079 µg/L), MTM (20.39 µg/L), or both in water and were fed on a basal diet only or taurine-supplemented basal diet. Exposure to LCT and MTM retarded growth and increased mortality rate. LCT and MTM reduced antioxidant enzyme activities (superoxide dismutase and glutathione peroxidase) and innate and humoral immunity but upregulated interleukin and chemokine expressions. Moreover, exposure to LCT and MTM elevated 8-OHdG levels and increased the mortality of Oreochromis niloticus after the experimental bacterial challenge. The TUR-enriched diet enhanced antioxidant enzymes and acted as a growth promoter and anti-inflammatory agent. TUR can modify innate and adaptive immune responses. Furthermore, TUR supplementation is a beneficial additive candidate for mitigating LCT and MTM toxicities mixed with O. niloticus aquafeed.

Fenpropathrin (FNP) is a member of the synthetic pyrethroids. Herein, the present study was conducted to investigate, for the first time, the potentially harmful effects of FNP on the reproductive system of male rats. In addition, the prophylactic or concurrent influence of camel milk (CM) was assessed. Adult male rats were divided into five groups; control, vehicle control (oil), CM (2ml/rat/day), FNP (15mg/kg bwt/60 days), CM/FNP (prophylaxis) and FNP /CM (co-treated) groups. Sperm morphology, count, serum testosterone (TES), luteinizing hormone (LH) and follicle-stimulating hormone (FSH), thiobarbituric acid reactive substances (TBARS), total antioxidant capacity (TAC), superoxide dismutase (SOD), testicular enzymes, and comet assay analysis were estimated. In addition, histopathology, the ultrastructure of testicular tissue and apoptosis were evaluated. Reduced body weight and gonadosomatic index were observed in the FNP exposed group. TES, LH, FSH were markedly declined following FNP treatment. SOD and TAC concentrations were reduced while PC and TBARS were significantly elevated in FNP group indicating oxidative stress. Furthermore, FNP induced DNA damage and apoptosis in the testis which was evidenced histopathologically and by electron microscope examination. CM significantly counteracted FNP reprotoxic effects, particularly at the prophylactic routine (CM/FNP) than the co-exposure (FNP/CM) one. Conclusively, these findings verified that CM could be a potential candidate therapy against FNP reprotoxic impacts.

Heavy metals (HM) are widespread contaminants of water affecting aquatic organisms and aquatic ecosystems. Indian lotus, Nelumbo nucifera (Gaertn.), is a beneficial medicinal plant that exhibits several pharmacological properties. It is hypothesized that incorporation of Indian lotus leaf (ILL) powder may be able to alleviate toxic effects exerted by a mixture of lead (Pb), cadmium (Cd), mercury (Hg), and zinc (Zn) in Nile tilapia, Oreochromis niloticus (L.). A total of two hundred and forty fish were randomly allocated into eight groups in triplicate, in a bifactorial design (4 ILL levels × 2 HM exposures). The fish in the first four groups were fed on a basal diet (39.9% crude protein) that was enriched with 0.0, 0.1, 0.2, and 0.4% ILL (in G1–G4, respectively), with no HM exposure. In the remaining four groups, fish were fed with the same diets and, in addition, were exposed to 1/20 of the 96 h-LC50 of Pb, Cd, Hg, and Zn mixture (in G5–G8, respectively), for 45 days. The HM exposure significantly elevated the levels of serum alanine and aspartate aminotransferases, creatinine, urea, malondialdehyde, and activities of catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPX). The expression level of hepatic metallothionein (MT) was up-regulated as well as high residual levels of HM in fish musculature were recorded in the HM-exposed fish. Two-way ANOVA revealed that all the studied variables were significantly affected by the ILL supplementation, HM exposure, and their interaction. Moreover, levels of MDA, CAT, SOD, and MT showed significant positive correlations with HM concentrations. Moreover, necrosis and degeneration of hepatopancreatic cells with congestion, hyperplasia, and fusion of gills lamellae were observed in HM-exposed fish. Interestingly, ILL supplementation, especially in the fish fed with 0.2 and 0.4% ILL, was observed to reduce the HM concentration in the fish body, resulting in the reduction of its toxic effects on the biochemical and antioxidant activities. These results demonstrated that dietary ILL supplementation could protect Nile tilapia against the toxic effects of HM, and therefore, may serve as a beneficial feed additive for application in the aquaculture industry.

Hypoxia-induced oxidative stress and apoptosis are the major hallmark explanations underlying brain dysfunction. Hypoxia in the current study was induced by Cobalt chloride (CoCl2) treatment in rats. The aim of this experiment was to explore the potential ameliorative potency of Moringa oleifera ethanolic extract (MO) against experimentally induced hypoxia on the structure and function of the rat’s brain. Fifty male rats were allocated to five groups (10 rats each): a control group, a MO-treated group (400 mg/kg bw, orally), a CoCl2-treated group (40 mg/kg bw/day, orally), a prophylaxis group, and a therapeutic co-treated group. Oxidative stress biomarkers and monoamine neurotransmitter were evaluated in brain tissue. In addition, qRT-PCR for expression pattern of HIF-1α, EPO, CYTO, NF-kB, and MAO-A. Glial fibrillary acidic protein (GFAP), apoptotic markers (BCL-2 and caspase 3) were detected immunohistochemically in brain cells. The results revealed a significantly lower concentration of GABA, monoamine neurotransmitter in hypoxic rat’s brain. Moreover, an evident up-regulation of the mRNA expression of HIF-1α, EPO, CYTO, NF-kB, and MAO-A. There was marked encephalopathy manifested by pyknotic neurons with eosinophilic cytoplasm, vacuolations and cerebral congestions in the hypoxic rat brains. Additionally, the score of neuronal expression occupied by GFAP- positive astroglia, Caspase-3 and microglial CD68 were elevated but Bcl-2 expression was found decreased in the hypoxic group than control. The endpoints of this study clearly stated that MO ethanolic extract suggestively counteracted neurotoxic impacts caused by hypoxia, particularly when it administered prior to and concurrently with CoCl2 administration.

Aims We investigate the consequence of adjuvant anastrozole (ANA) in monotherapy or associated with biochanin A (BCA) in ovariectomized (OVX) rat model and the degree of developing bone loss in both conditions. Materials and methods Sixty female rats were assigned to six groups. Five groups were bilaterally OVX, and one was sham operated. The five groups were; ANA group (0.5 mg/kg b.wt orally), BCA (5 mg/kg b.wt intraperitoneally (I/P), co-treated group (BCA + ANA), two control groups receiving even distilled water orally or DMSO I/P for twenty weeks. Bone turnover biomarkers BALP, OC, PTH, TRAP and TNFα were determined in serum. Bone mineral content, histological and morphometric measurements on rat femurs were performed. BMD by X-ray technique on tibias of rats and CT analysis of lumbar vertebrae of all treated and sham groups were applied. Key findings There was marked elevation in bone turnover biomarkers with high serum Ca and P content in the ANA-treated rats. Moreover marked elevation of TNFα, PTH, TC and TG, ANA caused severe changes in the BMD detected by X-ray in tibial bones and CT analysis of lumbar vertebrae of OVX rats. While I/P injection of BCA ameliorated the adverse bone health decrements caused by ANA. Significance The study highlights the importance of the BCA supplementation in accordance with the ANA therapy in case of ovariectomized rat model of osteoporosis which is clinically presented in Postmenopausal women with breast cancer during which considerable risk of developing osteoporosis is predicted during treatment.

One of the global alarming prevalent metabolic diseases is Type 2 diabetes mellitus (T2DM) than other diabetes and sustains a substantial burden on public and healthcare systems. This study attempts to endeavor the beneficial effect of chitosan stabilized nanoparticles Ch-SeNPs on combating diabetic nephropathy (DN) after induction of T2DM in rats (DN.STZ-induced T2D). High-fat diet (HFD) and STZ were used for the induction of T2DM in rats, and then they were treated with either metformin alone (MEF) (500 mg/kg b.wt.) or combined with (Ch-SeNPs) (2 mg Se/kg b.wt.) for eight weeks. The microvascular complications in renal tissue of diabetic rats were pronounced by the prevalence of microalbuminuria and elevated levels of urea, creatinine, and BUN. Pronounced oxidative stress with enhanced inflammatory response. In the urine of diabetic rats, a marked increase in Kim 1, β2-microglobulin, and urinary albumin. Renal morphological alterations were observed in all groups upon induction of T2DM, except for the Ch-SeNPs/MEF group showed noticeable improvements. The expression levels of Aldo-keto reductase AKr1B1, profibrotic protein transforming growth factor-β1 (TGF-β1), nestin, desmin, and vimentin, were up-regulated in the diabetic group. Significant down-regulation of their expression and restored antioxidant capacity was observed in the combined-treated group than single treated ones. Ch-SeNPs helped limit the prevalence of TNF-α, IL-6, and IL-1β while used after T2DM induction by STZ and HFD. Ch-SeNPs/MEF co-therapy could effectively guard the kidneys and reduce the renal tissue injury via inhibiting oxidative stress and restoring glucose hemostasis, which indicates a promising line for treating T2DM nephropathy.

Background Lead (Pb) and aluminum (Al) are ubiquitous environmental pollutants and are known to induce neurodegenerative disorders. They enhance neuronal changes and may involve glial alterations and other consequences. We intend to evaluate the mechanism through which the long-term exposure to Pb acetate alone or in combination with aluminum-chloride induced neurological impacts in rats. Methods For this aim, a total number of forty male Sprague Dawley rats were assigned into four groups. Control (DW), Pb acetate (12.5 mg/kg BW), Al chloride (64 mg/kg BW), and the combination group were experimentally exposed for 60 days. Biochemical evaluation of oxidative stress biomarkers, transcriptional-mediated changes in the expression pattern of OGG1 and P53 genes by qRT-PCR were applied. Histopathological modifications in the brain tissue with immunohistochemical reactivity of GFAP were also detected. Results Our findings revealed that lipid peroxidation was markedly enhanced but inhibited antioxidant enzyme activity in brain tissue in all exposed groups regarding the control. Pb-acetate elevated the biochemical concentration of dopamine and serotonin while AlCl3 declined their levels in the brain homogenate of rats. Furthermore, the exposure to one or both metals elevated the comet assay indices and serum level of 8-hydroxy-2′ –deoxyguanosine, up-regulated the expression of P53, OGG1 and GFAP immunoreactivity in the central nervous system. Histologically, they caused several brain tissue alterations. Conclusion The exposure to Pb and/or Al could be key candidates for neurodegenerative changes in the brain of rats via oxidative, apoptotic, and DNA damaging pathways. Besides, according to our findings, exposure to both Pb acetate and Aluminium chloride have synergistic damaging effects on the central nervous system of rats. Also, they have opposing effects on the secretion of monoamine neurotransmitters DA and 5 H T.

Background: this study examined the metformin (MF) and/or chitosan stabilized selenium nanoparticles (CH-SeNPs) efficacy to alleviate the male reproductive function impairment in a high-fat diet feed with low-dose streptozotocin (HFD/STZ) induced type 2 diabetes mellitus (T2DM) diabetic rat model. Methods: control non-diabetic, HFD/STZ diabetic, HFD/STZ+MF, HFD/STZ+CH-SeNPs, and HFD/STZ+MF+CH-SeNPs rat groups were used. After 60 days, semen evaluation, hormonal assay, enzymatic antioxidant, lipid peroxidation, testis histopathology, and the steroidogenesis-related genes mRNA expressions were assessed. Results: in the HFD/STZ diabetic rats, sperm count and motility, male sexual hormones, and testicular antioxidant enzymes were significantly reduced. However, sperm abnormalities and testicular malondialdehyde were significantly incremented. The steroidogenesis-related genes, including steroidogenic acute regulatory protein (StAr), cytochrome11A1 (CYP11A1), cytochrome17A1 (CYP17A1), and hydroxysteroid 17-beta dehydrogenase 3 (HSD17B3), and the mitochondrial biogenesis related genes, including peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC&alpha, ) and sirtuin (SIRT), were significantly downregulated in the HFD/STZ diabetic rats. However, CYP19A1mRNA expression was significantly upregulated. In contrast, MF and/or CH-SeNPs oral dosing significantly rescued the T2DM-induced sperm abnormalities, reduced sperm motility, diminished sexual hormones level, testicular oxidative damage, and steroidogenesis-related genes dysregulation. In the MF and CH-SeNP co-treated group, many of the estimated parameters differ considerably from single MF or CH-SeNPs treated groups. Conclusions: the MF and CH-SeNPs combined treatment could efficiently limit the diabetic complications largely than monotherapeutic approach and they could be considered a hopeful treatment option in the T2DM.

Cisplatin (CP) is an anticancer medication that is commonly used to treat solid tumors. Its use is, however, dose-restricted due to nephrotoxicity. We planned to compare the nephroprotective effects of three major compounds, including melatonin (MN), Ozone, or vitamin E, against the CP-induced renal damage in rats. CP was given once intraperitoneally (10 mg/kg,) eliciting acute kidney injury as assured by several adverse histological changes; glomerulopathy, tubulopathy, and vasculopathy, an inflammatory response including elevated TNF-α, IL-6, and IL-1β. Furthermore, biochemical alterations including, elevated plasma levels of urea, uric acid, creatinine, phosphorous, decreased plasma calcium levels, and gene expression abnormalities; upregulation of N-acetyl-β-d-glucosaminidase (NAG) and Transforming growth factor-β1 (TGF-β1), downregulation of CAT and SOD. Concurrent supplementation with either MN (10 mg/kg per os) or Ozone (1.1 mg/kg ip) and Vit E given by oral gavage (1 g/kg) for five consecutive days prior to CP injection and five days afterward displayed variable significant nephroprotective effects by mitigating the pro-inflammatory secretion, augmenting antioxidant competence, and modulating the gene expression in the renal tissue. The obtained biochemical, histological, and gene expression data suggested that MN had foremost rescue effects followed by Ozone then Vit E. MN's ameliorative effect was augmented in many indices including TNF-α, IL-6 , IL1-β, uric acid, creatinine, sNGAL and GGT, more than observed in Ozone, and Vit E therapy. A combination of these medications is expected to be more useful in relieving the damaging renal effects of CP given to cancer patients, pending further toxicological and pharmacological research.

The present study was carried out to explore a novel strategy with the hypothesis that the combined treatment with standard antidiabetic drug metformin (MET) and chitosan stabilized nanoparticles (CTS-Se-NPs) may have a potential role on insulin level, hepatic damage and apoptosis, and cardiac injury markers of type 2 diabetes mellitus (T2DM) in rat model. T2DM was induced by a high fat diet (HFD) for 8 weeks and a single injection of a low dose streptozotocin (STZ) (35 mg/kg) in Sprague Dawley rats. A total number of one hundred rats were divided into five groups; the first served as a control (non-diabetic) group and the other four groups served as diabetic rats. The treatments were even mono or combined therapy by CTS-Se-NPs and/or MET for 8 weeks. A group was given only MET (500 mg/kg bw/day), another was administered only CTS-Se-NPs at a dose of 2 mg se/kg/day, while the last group was given both of them (co-treated group). Biochemical, molecular and histopathological analyses were conducted to figure out the efficiency of the treatment by the monotherapeutic mode or combination therapy on the insulin level, oxidants/antioxidants status, inflammatory mediators, hepatic and cardiac injury biomarkers and apoptotic/anti-apoptotic gene expressions. Our results indicated that HFD/STZ-induced toxic effects on the serum, hepatic and cardiac tissues including a remarkable elevation of the oxidative and inflammatory mediators, and up-regulation of the apoptotic genes (Bax, Caspase-3, Fas, Fas-L) expression. Histologically, the heart tissue revealed various degenerative, vascular and inflammatory alterations characteristic to murine cardiomyopathy. Besides, livers from HFD-STZ-treated rats showed numerous cytotoxic, circulatory and inflammatory alterations. Combined therapy with MET and CTS-Se-NPs resulted in a better remarkable anti-diabetic effect demonstrated by substantial decreases in fasting blood glucose and insulin levels, and elevated with up-regulation of anti-apoptotic gene (BCL-2) and down-regulation of apoptotic genes after 8 weeks of treatment than that revealed in the monotherapeutic strategy. In addition, it ameliorated the damage of cardiac and hepatic tissues and reduced lipid accumulation, and pro-inflammatory cytokines levels and restored the antioxidant capacity. It could be concluded that, the combined strategy applied in the current study have a potential role to limit the diabetic complications and restore insulin resistance to a higher extent than monotherapeutic strategy and could be considered a promising therapeutic alternative in T2DM rat model.

This study explored the probable in vivo cardiac and renal toxicities together with in silico approaches for predicting the apoptogenic potential of Euphorbia peplus methanolic extract (EPME) in rats. Cardiac and renal injury biomarkers were estimated with histopathological and immunohistochemical evaluations of both kidney and heart. The probable underlying mechanism of E. peplus compounds to potentiate p53 activity is examined using Molecular Operating Environment (MOE) docking software and validated experimentally by immunohistochemical localization of p53 protein in the kidney and heart tissues. The gas chromatography/mass spectrometry analysis of E. peplus revealed the presence of nine different compounds dominated by di-(2-ethylhexyl) phthalate (DEHP). Significant elevations of troponin, creatine phosphokinase, creatine kinase&ndash, myocardium bound, lactate dehydrogenase, aspartate transaminase, alkaline phosphatase, urea, creatinine, and uric acid were evident in the EPME treated rats. The EPME treated rats showed strong renal and cardiac p53 expression and moderate cardiac TNF-&alpha, expression. Further, our in silico results predicted the higher affinity and good inhibition of DEHP, glyceryl linolenate, and lucenin 2 to the MDM2-p53 interface compared to the standard reference 15 a compound. Conclusively, EPME long-term exposure could adversely affect the cardiac and renal tissues probably due to their inflammatory and apoptotic activity. Moreover, the in silico study hypothesizes that EPME inhibits MDM2-mediated degradation of p53 suggesting possible anticancer potentials which confirmed experimental by strong p53 expression in renal and cardiac tissues.

Little is known regarding the impact of penoxsulam, a fluorinated benzenesulfonamid rice herbicide, on Oreochromis niloticus (O. niloticus). Therefore, the current study was undertaken to highlight the effects of penoxsulam exposure on O. niloticus and to evaluate the advantages of Chlorella vulgaris (CV) dietary supplementation against the induced effects. The 96-h lethal concentration 50 (LC50) penoxsulam value for O. niloticus was estimated at 8.948 mg/L by probit analysis in a static bioassay experiment. Next, 360 healthy fish were randomly allocated into 6 treatment groups. The T1 group served as the negative control and was fed a basal diet. The T2 group served as the positive control and was fed a basal diet supplemented with 10% CV. The fish in the T3 and T4 groups were exposed to 1/10 the 96-h LC50 of penoxsulam (0.8948 mg/L) and were fed the basal diet alone or the basal diet supplemented with 10% CV, respectively. The fish in the T5 and T6 groups were exposed to 1/5 the 96-h LC50 of penoxsulam (1.7896 mg/L) and fed the basal diet alone or the basal diet supplemented with 10% CV, respectively. Sub-acute penoxsulam exposure significantly altered hematological indices, as well as compromised the fish's immune defense mechanisms, including the phagocytic percentage, phagocytic index, nitric oxide production, immunoglobulin M levels and lysozyme, anti-trypsin and bactericidal activities subsequently decreasing O. niloticus's resistance to the Aeromonus sobria challenge and increasing disease symptoms and the mortality rate. Furthermore, sub-chronic penoxsulam exposure markedly altered growth performance, oxidant/antioxidant status and liver status and down-regulated the expression of interleukin-1β (IL-1β) and tumor necrosis-α (TNF-α). Interestingly, incorporating 10% CV into the diet protects fish against sub-acute penoxsulam-induced immunotoxicity via improvement of immune responses that increases the resistance against bacterial infection. Further, it improved the growth performance, oxidant/antioxidant status, liver status and markedly up-regulated immune-related gene expression, IL-1β and TNF-α, in the spleens of fish sub-chronically exposed to penoxsulam. These outcomes showed that dietary CV supplementation can protect the commercially valuable freshwater fish O. niloticus against penoxsulam toxicity and may be a potential feed supplement for Nile tilapia in aquaculture.

Antimicrobial resistance is a major public health and development concern on a global scale. The increasing resistance of the pathogenic bacteria Neisseria gonorrhoeae to antibiotics necessitates efforts to identify potential alternative antibiotics from nature, including insects, which are already recognized as a source of natural antibiotics by the scientific community. This study aimed to determine the potential of components of gut-associated bacteria isolated from Apis dorsata, an Asian giant honeybee, as an antibacterial against N. gonorrhoeae by in vitro and in silico methods as an initial process in the stage of new drug discovery. The identified gut-associated bacteria of A. dorsata included Acinetobacter indicus and Bacillus cereus with 100% identity to referenced bacteria from GenBank. Cell-free culture supernatants (CFCS) of B. cereus had a very strong antibacterial activity against N. gonorrhoeae in an in vitro antibacterial testing. Meanwhile, molecular docking revealed that antimicrobial lipopeptides from B. cereus (surfactin, fengycin, and iturin A) had a comparable value of binding-free energy (BFE) with the target protein receptor for N. gonorrhoeae, namely penicillin-binding protein (PBP) 1 and PBP2 when compared with the ceftriaxone, cefixime, and doxycycline. The molecular dynamics simulation (MDS) study revealed that the surfactin remains stable at the active site of PBP2 despite the alteration of the H-bond and hydrophobic interactions. According to this finding, surfactin has the greatest antibacterial potential against PBP2 of N. gonorrhoeae.

This study aimed to assess the potential apoptotic and oxidative damaging impacts of Triclosan (TCS) and Sodium Fluoride (NaF) administered separately or in combination, in rats for thirty days. For this purpose, forty immature female Sprague-Dawley rats were equally allocated into five groups. TCS group administered 185 mg TCS/kg Bw dissolved in distilled water (DW), while its control group received only DW. NaF group was given 50 mg/kg NaF in corn oil BW and its respective control had corn oil alone. The co-treated group was administered TCS and NaF. The oxidative stress biomarkers were evaluated in lung tissue homogenate and apoptotic proteins (BcL-2 and Caspase-3) expression were quantified in lung tissues. The results of TCS or NaF treated groups revealed a prominent depletion of super oxide dismutase (SOD), Catalase (CAT) and Glutathione (GSH) in lung tissue homogenate. On contrary, a marked increase in the tissue levels of Malondialdehyde (MDA) and lactate dehydrogenase (LDH) enzymatic assay levels. The co-exposed group evoked less severity in the oxidative stress biomarkers concentration than individually exposed groups. The apoptotic genes protein expression was significantly higher in TCS or NaF treated rats when compared to the control with intense to moderate immunolabeling of the bronchiolar lining epithelium and surrounding mononuclear inflammatory cells. On the contrary, no significant differences were detected in the expression of the investigated apoptotic biomarkers between the control and the combined exposed group. We concluded that the exposure to either TCS or NaF resulted in significant perturbations in lung tissue after short term oral administration at variable instances but the co-exposure resulted in less severe toxicological consequences.

This study aimed to evaluate the adverse effects of the insecticide imidacloprid (IMI) on male spermatogenesis, steroidogenesis, and DNA damage in sexually mature and immature rats. Forty male rats (mature and immature) were equally divided into four groups: two mature and two immature groups. IMI groups of both ages were orally administered IMI in corn oil at a concentration of 1 mg/mL for kg BW/day, whereas their respective controls were orally administered corn oil only (1 mL/kg of body weight) daily for 65 days. On day 66, the rats were lightly anesthetized and then euthanized by cervical dislocation. Whole blood was collected for hemogram, serum for hormonal profile, semen for sperm profile, and testes for gene expression and histopathological, and immunohistochemical examinations. The obtained results revealed that both sexually mature and immature rats orally exposed to IMI showed serious abnormalities in sperm morphology and concentrations, with an imbalance of sexual hormones. There were increases in the level of serum 8-hydroxy-2′-deoxyguanosine and in the percentage of comet (tailed) sperm DNA in the IMI-treated groups. The results exhibited the upregulation of a DNA damage tolerance gene (8-oxoguanine glycosylase 1) and downregulation of the activity of steroidogenic genes (nuclear receptor subfamily 5, group A, member 1 and 3β-hydroxysteroid dehydrogenase). Immunohistochemical examination of the B-cell lymphoma 2-associated X apoptotic protein in testicular sections showed various degrees of apoptosis in the spermatogonial cells of the IMI-treated rats compared to the control groups. These damaging effects of IMI were more pronounced in the sexually mature rats than in the immature rats. In conclusion, despite using a low dose of IMI in the present study, there were noticeable harmful consequences on the reproductive system at different stages of sexual maturity in male rats.

Currently, feed adulteration and contamination with melamine (MEL) are considered one of the serious issues in the aquatic industry. With the limited studies of MEL exposure alone in fish, its adverse impacts on fish cannot be evaluated well. Accordingly, this study aimed to investigate the effects of MEL containing diets on the immune response, disease resistance to Aeromonas hydrophila, growth performance, chemical composition, immune-related genes expression, and histopathology of both spleen and head kidneys. Also, the efficacy of curcumin (CUR) dietary supplementation to alleviate MEL negative impacts were evaluated. A total of 180 apparently healthy Oreochromis niloticus (O. niloticus) were divided into four groups with three replicates fed the basal diet only, basal diet fortified with 200 mg/kg CUR, basal diet containing 1 % MEL, or a basal diet containing CUR + MEL. The results displayed that MEL significantly reduced growth performance indices and body crude lipid contents. Anemic, leukopenic, lymphocytopenic, heterocytopenic, esonipenic, hypoproteinemic and hypoalbuminic conditions were apparent. Moreover, depleted immune and antioxidant indicators including lysozyme activity, nitric oxide, immunoglobulin M, complement 3, glutathione peroxidase, and superoxide dismutase enzyme activity were recorded. Also, MEL reduced the disease resistance of O. niloticus to bacterial infection. Furthermore, MEL induced downregulation of mRNA levels of interleukin 1β and tumor necrosis factor α in the spleen together with obvious pathological perturbations in both spleen and head kidneys. The CUR addition resulted in a significant enhancement in most indices. These results may conclude that MEL could alter both innate and adaptive immune responses via the negative transcriptional effect on immune-related genes together with the oxidative damage of the immune organs. Furthermore, CUR dietary supplements could be advantageous for mitigating MEL negative impacts, thus offering a favorable aquafeed additive for O. niloticus.

The present study evaluated the adverse effects of the hexavalent chromium (Cr (VI)) at sub-lethal concentrations and the ameliorative potential of curcumin (CUR) over a sub-chronic exposure period on Oreochromis niloticus. Fish were exposed to Cr (VI) (4.57 mg/L) and CUR (0.02% in diet or 200 mg/kg diet), individually or in combination for 60-days. The growth rate during the period of experiment, condition factor, body composition, hepatosomatic index (HSI), hematological parameters, oxidative stress, apoptotic and DNA damage, branchial, hepato- and nephrotoxicity were estimated in this study. Moreover, the changes in mRNA expression of Cytochromes (CYP450) and glutathione S-transferase (GST) in kidney and liver tissues were assessed by qRT-PCR. Additionally, the concentration of metallothionine in the liver, histological investigation, and lesion scoring to the branchial, hepatic, renal and gill tissues were applied. The results revealed that Cr (VI) exposure caused a significant decline in most hematological variables and growth rate with down-regulation of CYP450 and GST expression. Histologically, Cr (VI) induced diverse forms of cell injury, vascular, and inflammatory alterations with upregulation of caspase-3 and downregulation of Bcl2 expression in the examined tissues. Additionally, it elevated the levels of serum MDA and 8-hydroxy-2' -deoxyguanosine than control. CUR-supplementation resulted in a significant improvement in most indices, amelioration of histological alterations and up-regulation of CYP450 and GST expression. These results may conclude that dietary supplements with CUR could be useful for modulation of the growth with protective effects to the branchial, hepatic, and renal tissues in response to Cr (VI) exposure, thereby presenting a promising feed additive for Nile tilapia in aquaculture.

Currently, the contamination of water with different insecticides like profenofos (PFF) is a critical concern in the aquatic ecosystem. There are limited studies available on the negative impacts of PFF on common carp fish (Cyprinus carpio L.). Therefore, the existing study was designed to investigate the effect of PFF exposure (1/10 of the 96 h-LC50) on the neurobehavior, growth performance, chemical composition, oxidative status, DNA damage, apoptotic status and histological indices of the brain and gill tissues. In addition, this study seeks to detect the ability of geranium essential oil (GEO) dietary supplementation to mitigate the negative impacts of PFF. Accordingly, a total of 120 healthy fish were divided into four groups: the control group, fed on basal diet only; the other groups were fed on a basal diet supplemented with 400 mg kg-1 GEO, basal diet and PFF in water (PFF group), and supplemented diet with GEO and PFF in water (GEO + PFF), respectively, for 60 days. The results showed that PFF significantly reduced fish growth performance, crude protein, and lipid contents. It caused several behavioral alterations including spiral movement, decreased activeness, and changes in feeding behavior. Moreover, PFF increased the DNA tail length, tail moment, and the level of 8-hydroxy-2'-deoxyguanosine. Histologically, PFF induced a wide array of circulatory, inflammatory, regressive and progressive alterations in the brain and gill tissues. PFF significantly downregulated Bcl-2 and upregulated caspase-3 immuno-expression in both organs. Further, it considerably depleted the antioxidant enzymes, including superoxide dismutase, catalase, and glutathione peroxidase. The GEO supplementation did not reach the respective control values but markedly improved most of the behavioral, physical, biochemical, oxidative, apoptotic, and inflammatory markers, altered by PFF exposure. It also protected the gill and brain tissues from the branchial and encephalopathic effects of PFF. These findings suggest that GEO dietary supplements could be advantageous for mitigating PFF negative impacts and presenting a promising feed additive for common carp in aquaculture.

The present study investigated the possible effect of profenofos (PFF) on hepato-renal functions, non specific-immunity, and oxidants/antioxidants status in common carp, Cyprinus carpio (L.), and the supportive role of geranium (Pelargonium graveolens) essential oil (GEO). A static 96-h acute toxicity test was performed to determine the 96-h LC50 of PFF in common carp fingerlings and it was found to be 47.46 μg L−1 calculated by Finney probit analysis. One hundred and twenty fish were randomly allocated into four groups in triplicate. The first served as control and second groups were fed on basal diets that were enriched with 0.0 and 400 mg kg−1 of diet GEO, respectively without PFF exposure. The third and fourth groups were fed on the same diets and in addition, were exposed to 1/10 of the 96 h-LC50 of PFF (4.74 μg L−1), respectively for 60 days. The results revealed that the PFF exposure induced marked increases in the levels of serum alanine and aspartate aminotransferases (ALT and AST), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), creatinine, urea, cholesterol, triglycerides (TG), and malondialdehyde (MDA). Meanwhile, the serum total protein (TP), globulins, glucose, lysozyme activity, complement3 (C3), nitric oxide (NO), and hepatic antioxidant enzyme activities as well as the reduced glutathione (GSH) content were markedly declined in the PFF-exposed fish compared to the control group. Additionally, vacuolation, pyknosis, and degeneration of hepatocytes and epithelial cells of renal tubules with mononuclear cell infiltration were observed. A strong caspase-3 and weak BCL-2 immunohisto-reactivity in the liver and kidney tissues of PFF-exposed fish were noted respective to the control. Interestingly, GEO supplementation improved these variables with nearly restoring to control values with improving the histological architecture of liver and kidney tissues. The apoptotic condition of the examined tissues was markedly restricted in the combination group than PFF-exposed group. These results concluded that GEO has ameliorative influence against toxic impacts of PFF on hepato-renal functions, immunological parameters, and oxidative stress in common carp, and therefore, maybe a valuable candidate as a dietary supplement in aquaculture.

Hypoxia-induced oxidative stress and apoptosis are the major hallmark explanations underlying brain dysfunction. Hypoxia in the current study was induced by Cobalt chloride (CoCl

Aims This study was designed to assess the beneficial role of biochanin A (BCA) in the protection of the cutaneous and renal tissues of ovariectomized rats, even in those treated with anastrozole (ANA). Materials and methods For this purpose, 60 adult female Wistar rats were allocated into 6 equal groups. Rats in group I (sham) underwent a sham operation and received distilled water orally. In groups II and III, OVX rats received either distilled water orally or DMSO intraperitoneally, respectively. In groups IV and V, OVX rats were either treated orally with 0.5 mg ANA/kg.b.wt. or administered 5 mg of BCA/kg.b.wt. intraperitoneally, respectively. In group VI (OVX-ANA-BCA), OVX rats were co-treated with BCA and ANA. All treatments were given daily for 20 weeks. Key findings The IP administration of BCA significantly decreased serum levels of urea, creatinine, uric acid and MDA and significantly increased serum CAT, GSH and TAC and cutaneous IL-4 and GATA3 concentrations in the fifth and sixth groups compared to OVX-DMSO and OVX-ANA groups, respectively. Additionally, it induced down-regulation of renal TNF-α and iNOS expression as well as up-regulation of cutaneous TGF-β expression. Furthermore, BCA ameliorated to variable degrees histological changes of renal and cutaneous tissue related to ovariectomy and/or ANA treatment. Significance These data suggest that BCA might be a useful alternative estrogen therapy for the management of renal and cutaneous changes observed in postmenopausal women, even in those treated with ANA.

The present study declares the relationship between the cause of death and postmortem biochemical marker alterations in CSF, serum and plasma. In addition, immunohistochemical and microarchitecture examination of brain tissue of White New Zealand rabbits at different PMI after traumatized death. Thirty adult male White New Zealand rabbits were divided into two main equal groups; the first was physically killed by cervical dislocation and the second through head trauma. Each group was subdivided into three PMIs (zero, 6, and 12hrs PM). CSF was used to detect the levels of K+, Na+, Ca++, albumin While, lactic acid, hypoxanthine, ammonia and uric acid concentrations were measured in plasma. Estimation of HMGB1, IL-1β and TNF-α were assessed in serum. In addition to immunohistochemical observations of Bcl-2 and P53 apoptotic proteins in brain tissue. The results revealed that some of the examined parameters as K+, Na+, albumin, ammonia, hypoxanthine and HMGB1 had the potential role in estimation of PMI at examined time periods in physical and traumatized death. Traumatic death induced severe cerebral hemorrhages and necrosis of cerebral parenchyma than physical death. Immunohistochemical results of P53 and Bcl-2 in brain tissue declared focal positive reactions of some neurons, astrocytes and microglia in different degrees with time since death. It was concluded that biochemical analysis of some body fluids, tissue pathological changes and apoptotic markers are applicable tools for assessing accurate PMI after traumatic brain injury and could have a crucial role in legal medicine

This study is aimed to evaluate the possible neurotoxic effect of tartrazine (T), an extensively used synthetic azo dye, as well as to determine the potential modulatory role of cod liver oil (CLO) or royal jelly (RJ) against such effects. For this purpose, thirty-six male rat pups were allocated into six groups. The 1st group received distilled water (control group), the 2nd group was given 300 mg RJ/kg bw (RJ group), the 3rd group was given 0.4 ml CLO/kg bw (CLO group), the 4th was given 500 mg T/kg bw (T group). The 5th group was given T concurrently with RJ (TRJ group) and the 6th group was given T concurrently with CLO (TCLO group), at the same doses as the former groups. All treatments were given orally for 30 consecutive days. The concentrations of different brain neurotransmitters, gamma amino butyric acid (GABA), dopamine (DA) and serotonin (5HT) as well as the antioxidant and oxidative stress biomarkers were measured in the brain homogenates. An immunohistochemical staining of the cerebral cortex was applied with the anti-ssDNA antibody (an apoptotic cell marker) to reveal the changes in brain structure. The T group revealed a significant decrease in the concentration of the brain neurotransmitters, a sharp shortage in the level of antioxidant biomarkers (super oxide dismutase, catalase and the reduced glutathione), a marked increase in malondialdehyde levels, and numerous apoptotic cells in the brain cortex compared with the other groups. Interestingly, all the previously mentioned parameters were almost retrieved in both the TRJ and TCLO groups compared to the T group. These results conclusively demonstrate that RJ and CLO administration provides sufficient protection against the ruinous effects of T on rat pups brain tissue function and structure.