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西红花苷通过维持谷胱甘肽氧化还原系统减轻环磷酰胺诱导的睾丸毒性。

Crocin attenuates cyclophosphamide induced testicular toxicity by preserving glutathione redox system.

机构信息

Department of Pharmacology, St. Paul's College of Pharmacy, Turkayamjal, Hyderabad, Telangana, India.

Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research, Balanagar, Hyderabad, Telangana, India.

出版信息

Biomed Pharmacother. 2018 May;101:174-180. doi: 10.1016/j.biopha.2018.02.068. Epub 2018 Feb 24.

DOI:10.1016/j.biopha.2018.02.068
PMID:29486335
Abstract

Chemotherapy induced testicular toxicity is an emerging reason for azoospermia and impotency in males. Cyclophosphamide (CP) is a widely used chemotherapeutic agent to manage neoplastic and non-neoplastic autoimmune diseases. Testicular toxicity along with bladder and hepatotoxicity are its widely reported adverse effects. Crocin (CR) is the digentiobiosyl ester of crocetin, found in the fruits of gardenia (Gardenia jasminoides E.) and dried stigmas of saffron (Crocus sativus L.) possess antioxidant, anti-depressant, anti-tumor and aphrodisiac properties. In the light of these reports, the present study aimed to investigate protective effect of CR administration (10 mg/kg and 20 mg/kg per day for eight weeks) on CP induced (15 mg/kg per week for eight weeks) testicular toxicity in male Sprague dawley rats by analysing the Glutathione redox cycle, Sperm quality, spermatogenic and steroidogenesis hormonal axis, caspase 3 activity and histological investigations. Administration of CR preserved the glutathione redox cycle, sperm quality, hormonal mediators associated with sperm production. It also decreased testicular apoptosis as evident from the reduction of caspase 3 activity. These biochemical findings were well reflected on the histo-pathological investigation. Conclusively, the results of this study indicate that administration of CR can dose dependently attenuate the toxic effects of CP on testis.

摘要

化疗引起的睾丸毒性是男性无精子症和阳痿的一个新出现的原因。环磷酰胺(CP)是一种广泛用于治疗肿瘤和非肿瘤自身免疫性疾病的化疗药物。睾丸毒性以及膀胱和肝毒性是其广泛报道的不良反应。藏红花酸(CR)是西红花酸的二葡萄糖基酯,存在于栀子(栀子 jasminoides E.)的果实和藏红花(番红花 sativus L.)的干燥柱头中,具有抗氧化、抗抑郁、抗肿瘤和壮阳作用。鉴于这些报道,本研究旨在通过分析谷胱甘肽氧化还原循环、精子质量、生精和类固醇生成激素轴、caspase 3 活性和组织学研究,探讨 CR 给药(每天 10mg/kg 和 20mg/kg ,持续 8 周)对 CP 诱导的雄性 Sprague dawley 大鼠睾丸毒性(每周 15mg/kg ,持续 8 周)的保护作用。CR 的给药保存了谷胱甘肽氧化还原循环、精子质量、与精子生成相关的激素介质。它还降低了睾丸细胞凋亡,这从 caspase 3 活性的降低可以明显看出。这些生化发现很好地反映在组织病理学研究上。总之,这项研究的结果表明,CR 的给药可以剂量依赖性地减轻 CP 对睾丸的毒性作用。

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