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二烯丙基二硫对铅诱导的大鼠睾丸氧化损伤、细胞凋亡及 CYP19 基因表达下调的保护作用。

Protective effect of diallyl sulfide against lead-mediated oxidative damage, apoptosis and down-regulation of CYP19 gene expression in rat testes.

机构信息

Department of Biochemistry, Faculty of Science, Mansoura University, Eldakahliya, Egypt.

Department of Biochemistry, Faculty of Veterinary Medicine, Kafr-Elsheikh University, Egypt.

出版信息

Life Sci. 2019 Jun 1;226:193-201. doi: 10.1016/j.lfs.2019.04.020. Epub 2019 Apr 12.

DOI:10.1016/j.lfs.2019.04.020
PMID:30986445
Abstract

AIMS

The present study aimed to investigate the potential therapeutic effect of diallyl sulfide (DAS), a natural component of garlic (Allium sativum), in the improvement of lead (Pb)-induced testicular toxicity and its underlying mechanisms.

MATERIALS AND METHODS

Thirty-two male albino rats were randomly divided into control, PbAc (20 mg lead acetate/kg bwt, orally), DAS (200 mg/kg bwt, orally), and PbAc + DAS groups for 49 successive days. The investigation based on the following criteria: Paired testes and epididymides weights, epididymal sperm analysis, level of serum sex hormones (Testosterone and17β-estradiol (E2)), aromatase (CYP19) expression, Malondialdehyde (MDA), Nitric oxide (NO), Superoxide dismutase (SOD) enzyme, reduced glutathione (GSH), testicular histopathology, spermatogenesis score and apoptosis detection (Caspase-3 immunoexpression).

KEY FINDINGS

Pb caused significant decline in epididymal sperm count and motility, testes and epididymes weights, spermatogenesis score and serum testosterone and1E2, as well as a significant decrease in SOD and GSH level, and a significant elevation of MDA and NO compared to a control group. In addition, Pb induced significant downregulation of CYP19 gene expression, increase of Caspase-3 immunoreactivity, various testicular degenerative and necrotic changes. Whereas, co-treatment of rats with DAS improved sperm analysis, and testicular histology and antioxidative status. Furthermore, DAS co-administration regulated testicular CYP19 and Caspase-3 expressions.

SIGNIFICANCE

Collectively, DAS seemed to be a promising agent for protection against Pb-induced testicular toxicity through antioxidative properties, beside regulation of testicular apoptosis and aromatase expression.

摘要

目的

本研究旨在探讨大蒜(Allium sativum)天然成分二烯丙基二硫(DAS)在改善铅(Pb)诱导的睾丸毒性及其潜在机制方面的潜在治疗效果。

材料和方法

32 只雄性白化大鼠随机分为对照组、PbAc(20mg 醋酸铅/公斤体重,口服)、DAS(200mg/kg 体重,口服)和 PbAc+DAS 组,连续 49 天。研究基于以下标准:配对睾丸和附睾重量、附睾精子分析、血清性激素(睾酮和 17β-雌二醇(E2))水平、芳香酶(CYP19)表达、丙二醛(MDA)、一氧化氮(NO)、超氧化物歧化酶(SOD)酶、还原型谷胱甘肽(GSH)、睾丸组织病理学、精子发生评分和凋亡检测(Caspase-3 免疫表达)。

主要发现

与对照组相比,Pb 导致附睾精子计数和活力、睾丸和附睾重量、精子发生评分以及血清睾酮和 1E2 显著下降,SOD 和 GSH 水平显著降低,MDA 和 NO 显著升高。此外,Pb 诱导 CYP19 基因表达显著下调,Caspase-3 免疫反应性增加,各种睾丸退行性和坏死变化。然而,DAS 治疗可改善精子分析和睾丸组织学以及抗氧化状态。此外,DAS 联合给药调节睾丸 CYP19 和 Caspase-3 的表达。

意义

总的来说,DAS 似乎是一种有前途的药物,可通过抗氧化特性,以及调节睾丸细胞凋亡和芳香酶表达来预防 Pb 诱导的睾丸毒性。

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