N-acetylcysteine and zinc sulphate abate di-2-ethylhexyl phthalate-mediated reproductive dysfunction in rats:Focus on oxidative and sex hormone receptors mechanisms

Objective:To investigate the potential of N-acetylcysteine(NAC)and zinc sulphate(ZnSO_(4))in mitigating reproductive dysfunction caused by di-2-ethylhexyl phthalate(DEHP)in rats and to understand the underlying mechanisms,specifically oxidative stress and sex hormone receptor activity.Methods:Thirty-five male Wistar rats were randomly divided into five equal groups(n=7 per group).Group 1 was administered 0.5 mL of distilled water and served as the control group.Group 2 was given only DEHP(750 mg/kg/day),while group 3,4 and 5 were given DEHP(750 mg/kg/day)plus NAC(100 mg/kg/day),DEHP(750 mg/kg/day)plus ZnSO_(4)(0.5 mg/kg/day),and DEHP(750 mg/kg/day)plus NAC(100 mg/kg/day)as well as ZnSO_(4)(0.5 mg/kg/day),respectively.All treatments lasted for 21 days.Samples were obtained after the rats were sacrificed,and hormones levels in the serum and markers of oxidative stress in the testicles were analyzed using the enzyme-linked immunosorbent assay.The amount of androgen receptors in the testicles was determined by immunohistochemistry,and the susceptibility of testosterone and DEHP to bind to androgen receptor and 5α-reductase was determined by molecular docking studies.Results:DEHP decreased reproductive hormones,testicular antioxidant enzymes,increased malondialdehyde levels,and negatively impacted histology of the pituitary and testes.NAC or ZnSO_(4) treatment showed a marked improvement in testicular antioxidant status and hormone levels,as well as a positive effect on the histology of the pituitary and testes.The combination of both treatments appeared to be more effective.The affinity of DEHP to bind to androgen receptors may lead to disruption of androgen receptor signaling,which can further result in dysfunction of hormones related to androgen.However,NAC is more likely to form stronger binding interactions with follicle stimulating hormone and luteinizing hormone receptors,as well as gonadotropin-releasing hormone receptors,when compared to DEHP.Conclusions:The possibility that NAC and ZnSO_(4) could downregulate DEHP-induced sex hormone changes is suggested by their potential to reduce toxicity.

Modulations in Anti-Oxidant Activities of Selected Gastro-Intestinal Tissues in Alloxan-Induced, Silymarin Treated Diabetic Wistar Rats

Diabetes mellitus (DM) is reportedly the commonest metabolic disorder with multi organ involvement. By inducing DM (with Alloxan) in Wistar rats, current study investigated the changes in antioxidant activities of selected gastrointestinal (GI) tissues [stomach, duodenum, pancreas and liver], upon treatment with Silymarin and/or Vitamin C. One hundred and twenty five (125) adult male wistar rats of between 130 to 180 grams were procured for the study. Five units of one control and four experimental units were designated with twenty five (25) rats per group (n = 25);Unit 1: Control rats, Unit 2 were DM induced, Silymarin untreated rats, and Units 3, 4 and 5 were DM induced, vitamin C, Silymarin and Vitamin C + Silymarin treated respectively. Following four (4) weeks of administration of test substance(s), rats were euthanized and blood samples obtained for biochemical and antioxidant assay on aforementioned GI tissues. One way analysis of variance (ANOVA) and Students t-test at p p < 0.05) at comparison of extract treated unit to control. Study also observed a significant change in pancreatic, liver, and duodenal anti-oxidant marker levels with Vitamin C, Silymarin and Vitamin C + Silymarin co-administrations to diabetic rats. It can therefore be said, that DM caused a destructive alteration pancreatic histo-architecture with improved functional capabilities in wistar rats at administration of Silymarin and vitamin C. Thus, Silymarin posed antioxidant potentials, with ameliorated pancreatic dysfunctions.