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

作　　者：Victor Oghenekparobo Emojevwe Mega Obukohwo Oyovwi Kayode Ezekiel Adewole Peggy Ejiro Ohwin Adeniran Oluwadamilare Akinola Alexander Obidike Naiho Eze Kingsley Nwangwa Victor Omo-Idonije Motunrayo Lade-Ige Benneth Ben-Azu 

机构地区：[1]Department of Physiology,University of Medical Sciences,Ondo City,Ondo State,Nigeria [2]Department of Physiology,Delta State University,Abraka,Delta State,Nigeria [3]Department of Physiology,Adeleke University,Ede,Osun State,Nigeria [4]Department of Biochemistry,University of Medical Sciences,Ondo City,Ondo State,Nigeria [5]Department of Pharmacology,Delta State University,Abraka,Delta State,Nigeria

出　　处：《Asian pacific Journal of Reproduction》2024年第5期228-240,共13页亚太生殖杂志（英文版）

摘　　要：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 downregula

关 键 词：Di-2-ethylhexyl phthalate TESTOSTERONE Androgen receptor 5Α-REDUCTASE OESTROGEN Luteinizing hormone 

分 类 号：R71[医药卫生—妇产科学] R69[医药卫生—临床医学]