IntroductionCadmium (Cd) is a highly toxic heavy metal that can be found everywhere in the environment and can have harmful effects on both human and animal health. Pinostrobin (PSB) is a bioactive natural flavonoid isolated from Boesenbergia rotunda with several pharmacological properties, such as antiinflammatory, anticancer, antioxidant, and antiviral. This investigation was intended to assess the therapeutic potential of PSB against Cd-induced kidney damage in rats.MethodsIn total, 48 Sprague Dawley rats were divided into four groups: a control, a Cd (5 mg/kg), a Cd + PSB group (5 mg/kg Cd and 10 mg/kg PSB), and a PSB group (10 mg/kg) that received supplementation for 30 days.ResultsExposure to Cd led to a decrease in the activities of catalase (CAT), glutathione reductase (GSR), superoxide dismutase (SOD), and glutathione peroxidase (GSH-PX), whereas levels of reactive oxygen species (ROS) and malondialdehyde (MDA) increased. Cd exposure also caused a substantial increase in urea, kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), and creatinine levels. Moreover, a noticeable decline was noticed in creatinine clearance. Moreover, Cd exposure considerably increased the levels of inflammatory indices, including interleukin-1b (IL-1b), tumor necrosis factor-a (TNF-a), interleukin-6 (IL-6), nuclear factor kappa-B (NF-kB), inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) activity. Cd treatment decreased the expression of the antiapoptotic markers (Bcl-2) while increasing the expression of apoptotic markers (Bax and Caspase-3). Furthermore, Cd treatment substantially reduced the TCA cycle enzyme activity, such as alpha-ketoglutarate dehydrogenase, succinate dehydrogenase, malate dehydrogenase, and isocitrate dehydrogenase. Moreover, mitochondrial electron transport chain enzymes, succinatedehydrogenase, NADH dehydrogenase, cytochrome c-oxidase, and coenzyme Q-cytochrome reductase activities were also decreased following Cd exposure. PSB administration substantially reduced the mitochondrial membrane potential while inducing significant histological damage. However, PSB treatment significantly reduced Cd-mediated renal damage in rats.ConclusionThus, the present investigation discovered that PSB has ameliorative potential against Cd-induced renal dysfunction in rats.

Background Male reproductive damage is one of the most adverse side effects of doxorubicin (DOX). Isorhamnetin is a natural flavonoid, which displays remarkable antioxidant potential. Objective The current research was designed to assess the protective effects of Isorhamnetin against DOX-instigated testicular damages. Methods Adult male Wistar rats (n=32) were divided into 4 groups: control, DOX (3 mg/kg i.p. 3 doses each after 1 week), DOX + Isorhamnetin (3 mg/kg 3 doses each after 1 week +10 mg/kg i.p. daily for 28 days, respectively), and Isorhamnetin (10 mg/kg i.p. per day). After 28 days of treatment, biochemical, spermatogenic, steroidogenic, hormonal, proapoptotic, antiapoptotic, and histopathological parameters were estimated. Results DOX exposure significantly decreased the activity of acid phosphatase, lactate dehydrogenase, and gamma-glutamyl transferase. Furthermore, DOX substantially decreased the activities of antioxidant enzymes, i.e. catalase, superoxide dismutase, glutathione reductase, and glutathione peroxidase along with protein content, whereas it increased the malondialdehyde level. It also reduced sperm progressive motility, viability, the number of hypoosmotic tail swelled spermatozoa, and epididymis sperm count and increased the sperm morphological anomalies (head, midpiece, and tail). Besides, it decreased the levels of follicle-stimulating hormone, luteinizing hormone, and plasma testosterone and lowered the expression of steroidogenic enzymes (3β-hydroxysteroid dehydrogenase, 17β-hydroxysteroid dehydrogenase, and steroidogenic acute regulatory protein) and testicular antiapoptotic marker (B-cell lymphoma 2) but increased the expression of proapoptotic markers (BCL2-associated X protein and caspase-3) along with histopathological impairments. However, isorhamnetin prevented all the damages caused by DOX. Conclusion Conclusively, Isorhamnetin can be used as a powerful mitigating agent to avert DOX-induced testicular damages.

Mentha longifolia L (ML) is locally used as an herbal contraceptive. We aim to assess the toxicity profile and validate the antifertility effects of its leaves in male rats. Adult male Sprague Dawley rats (n = 10 animals/group) were divided into four groups. The Control group received .9% saline, while groups II, III, and IV received 50, 75, and 100 mg/kg/day ML doses for 28 days. ML induced a dose-dependent decrease in percent fertility as well as the number of pups born in ML preexposed pairs, with maximum change observed in the ML3 group (60%, 3.75 ± 1.25) as compared to control (100%, 8.75 ± .48) group. A significant (P < .01) decrease in the rate of daily sperm production was observed in the ML3 group (.86 ± .16) in contrast to the control (2.93 ± .05). The levels of catalase and superoxide dismutase declined significantly in treatment groups (ML1-P < .001, ML2-P < .05, and ML3-P < .01). A significant increase in the production of reactive oxygen species (P < .001) was found in all treatment groups. The concentrations of LH (P < .001), FSH (P < .001), and testosterone (P < .001) were significantly reduced in a dose-dependent manner among ML-treated groups. Decreases in spermatogonial populations, mature spermatids, seminiferous tubule diameter, lumen diameter, and epithelial height were noticed at higher doses. The reversibility study depicted a reduction in both pregnancy outcomes and litter size. Besides contraceptive effects, M. longifolia L usage is associated with oxidative stress; therefore, it is important to consume this herb appropriately and its excessive usage should be prohibited.

Background: Polypropylene is a thermoplastic polymer playing the role of an endocrine disruptor that interferes with the union, emission, transport or elimination of normal hormones. Epidemiological information indicated the relation of endocrinedisturbing chemicals with prostate cancer, testis tumor and diminished fertility. p53 is a key tumor silencer gene. The present study aimed to evaluate luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels and the risk of p53 mutations as a result of exposure to polypropylene in non-tumorous adult male factory workers.Methods: In total, 150 (controls = 35, workers = 115) subjects were recruited.Groups were maintained according to the tenure of exposure G1 (1-5 years), G2 (6-10 years), G3 (11-15 years) and G4 (16-20 years). Concentrations of LH and FSH were determined through an enzyme-linked immunosorbent assay. Genotyping analysis was performed by polymerase chain reaction based gel electrophoresis followed by DNA sequencing. The structural and functional impact of the mutation on the p53 structure was evaluated using 50-ns molecular dynamics (MD) simulations and protein-DNA docking.Results: Mean plasma LH levels were significantly decreased in G1 (p > 0.05) as well as the G2, G3 and G4 (p > 0.001) groups. Similarly, FSH levels were significant decrease in G1 (p > 0.05), G2 (p > 0.01), G3 (p > 0.001) and G4 (p > 0.001) compared to the control group. Sequencing results found three variants i.e. g.13450 T>G, g.13430C>T and g.13737G>A. One of them was predicted to be disease-causing others are polymorphisms. MD simulation of missense mutation R273H showed no structural impact on the protein structure in MD simulation, but it resulted in weaker binding of p53 with the DNA that might lower the gene expression of cell cycle regulatory proteins.Conclusions: These findings predict decreased fertility and risk of malignancies in the future. The spectrum of p53 mutations as a result of polypropylene exposure in the Pakistani population has not been investigated before. Further studies and metaanalyses are required to elucidate the role of different plasticizers in reproduction and cancer-causing risk factors in a larger population.

An outbreak of pneumonia occurred on December 2019 in Wuhan, China, which caused a serious public health emergency by spreading around the globe. Globally, natural products are being focused on more than synthetic ones. So, keeping that in view, the current study was conducted to discover potential antiviral compounds from Allium sativum. Twenty-five phytocompounds of this plant were selected from the literature and databases including 3-(Allylsulphinyl)-L-alanine, Allicin, Diallyl sulfide, Diallyl disulfide, Diallyl trisulfide, Glutathione, L-Cysteine, S-allyl-mercapto-glutathione, Quercetin, Myricetin, Thiocysteine, Gamma-glutamyl-Lcysteine, Gamma-glutamylallyl-cysteine, Fructan, Lauricacid, Linoleicacid, Allixin, Ajoene, Diazinon Kaempferol, Levamisole, Caffeicacid, Ethyl linoleate, Scutellarein, and S-allylcysteine methyl-ester. Virtual screening of these selected ligands was carried out against drug target 3CL protease by CB-dock. Pharmacokinetic and pharmacodynamic properties defined the final destiny of compounds as drug or non-drug molecules. The best five compounds screened were Allicin, Diallyl Sulfide, Diallyl Disulfide, Diallyl Trisulfide, Ajoene, and Levamisole, which showed themselves as hit compounds. Further refining by screening filters represented Levamisole as a lead compound. All the interaction visualization analysis studies were performed using the PyMol molecular visualization tool and LigPlot+. Conclusively, Levamisole was screened as a likely antiviral compound which might be a drug candidate to treat SARS-CoV-2 in the future. Nevertheless, further research needs to be carried out to study their potential medicinal use.