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橙花叔醇对环磷酰胺诱导的瑞士白化病小鼠生殖毒性的改善作用:基于生化、组织学和免疫组织化学的证据。

Ameliorative effect of nerolidol on cyclophosphamide-induced gonadal toxicity in Swiss Albino mice: Biochemical-, histological- and immunohistochemical-based evidences.

机构信息

Department of Pharmacology, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi, India.

Department of Biotechnology, Jamia Millia Islamia, New Delhi, India.

出版信息

Andrologia. 2020 May;52(4):e13535. doi: 10.1111/and.13535. Epub 2020 Feb 12.

DOI:10.1111/and.13535
PMID:32048763
Abstract

Cyclophosphamide (CP) is commonly used as antineoplastic and immunosuppressant drug with noticeable gonadotoxic profile. Nerolidol (NER) is a sesquiterpene with potent antioxidant and anti-inflammatory properties. Thus, the present study was designed to explore its possible gonadal protective potential against cyclophosphamide-induced testicular, epididymal, seminal and spermatozoal toxicities. Animals were divided into five groups: control (normal saline for 14 days), treatment group (NER 200 and 400 mg/kg, p.o) for 14 days along with a single dose of cyclophosphamide (200 mg/kg, i.p) on 7 day, toxic and Per se groups (cyclophosphamide 200 mg/kg i.p) on 7 day and NER 400 mg/kg for 14 days respectively. Animals were sacrificed on the 15 day, and body weight, weight of reproductive organs, testosterone level, sperm count, biochemical parameters, histopathological and immunohistochemical studies were performed in the testes, epididymis and in the serum. CP administration induced oxidative stress, nitrative stress, inflammation, reduced testosterone level, sperm count, increased expression of MPO and caused histological aberrations in the testes, epididymis and seminal vesicles. CP caused reduced sperm count, sperm motility and testosterone level which got reversed upon treatment with nerolidol in a dose-dependent manner. Nerolidol thus acted as a gonadoprotective molecule and prevented the gonadotoxicity of CP.

摘要

环磷酰胺(CP)是一种常用的抗肿瘤和免疫抑制剂,具有明显的性腺毒性。橙花叔醇(NER)是一种具有强大抗氧化和抗炎特性的倍半萜烯。因此,本研究旨在探讨其对环磷酰胺诱导的睾丸、附睾、精液和精子毒性的可能性腺保护潜力。动物分为五组:对照组(生理盐水 14 天)、治疗组(NER200 和 400mg/kg,po)14 天,第 7 天单次腹腔注射环磷酰胺(200mg/kg),毒性组和单独给药组(环磷酰胺 200mg/kg,ip)第 7 天和 NER400mg/kg,分别给药 14 天。第 15 天处死动物,检测体重、生殖器官重量、睾酮水平、精子计数、生化参数、睾丸、附睾和血清的组织病理学和免疫组织化学研究。CP 给药诱导氧化应激、硝化应激、炎症、降低睾酮水平、精子计数、增加 MPO 表达,并导致睾丸、附睾和精囊的组织学异常。CP 导致精子计数、精子活力和睾酮水平降低,NER 以剂量依赖的方式治疗可逆转这些变化。因此,橙花叔醇是一种性腺保护分子,可防止 CP 的性腺毒性。

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