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己酮可可碱对顺铂诱导的大鼠睾丸毒性作用的评估

Evaluation of the Effect of Pentoxifylline on Cisplatin-Induced Testicular Toxicity in Rats.

作者信息

Fallahzadeh Ali Reza, Rezaei Zohreh, Rahimi Hamid Reza, Barmak Mehrazd Jafari, Sadeghi Hossein, Mehrabi Sadrollah, Rabani Seyed Mohammadreza, Kashani Iraj Ragerdi, Barati Vahid, Mahmoudi Reza

机构信息

Cellular and Molecular Research Center, Yasuj University of Medical Sciences, Yasuj, Iran.

Student Research Committee, Yasuj University of Medical Sciences, Yasuj, Iran.

出版信息

Toxicol Res. 2017 Jul;33(3):255-263. doi: 10.5487/TR.2017.33.3.255. Epub 2017 Jul 15.

Abstract

Chemotherapy is associated with male infertility. Cisplatin (cis-diamminedichloro-platinum (II) (CDDP) as a chemotherapy medication used to treat a number of cancers has been reported to most likely induce testicular toxicity. Administration of antioxidants, such as pentoxifylline (PTX) may reduce some Adverse Drug Reactions (ADRs) of CDDP. Therefore, this study investigated the potentially protective effects of PTX on CDDP-induced testicular toxicity in adult male rats. For this purpose, 42 male rats were randomly divided into 7 groups. The rats were orally pretreated with PTX at the 3 doses of 75, 150, and 300 mg/kg once a day for 14 successive days. On the 14 day of the study, they were intraperitoneally (IP) administered with a single dose of CDDP (7 mg/kg). Finally, the sperm/testis parameters, serum levels of reproductive hormones, including testosterone, Luteinizing Hormone (LH), and Follicle Stimulating Hormone (FSH) as the pivotal endocrine factors controlling testicular functions, and histopathological changes of testis tissue were examined. Pretreatment with the two doses of 75 and 150 mg/kg PTX indicated significant increases in the sperm count and motility induced by CDDP administration. The right and significantly left testis weights were decreased following the treatment with 300 mg/kg of PTX plus CDDP. However, 75 mg/kg of PTX plus CDDP showed the best near-to-normal histopathological features. The results demonstrated that PTX alone enhanced some parameters, such as the sperm count, while reducing other parameters, including sperm fast motility and germ layer thickness. Furthermore, despite testosterone or LH levels, the mean serum FSH level was significantly augmented by the doses of 75 and 150 mg/kg. It was concluded that PTX administration cannot reduce CDDP-induced testicular toxicity even at high doses (e.g., 300 mg/kg), while it seemed to partially intensify CDDP toxicity effects at a dose of 75 mg/kg. Thus, further research is required in this regard.

摘要

化疗与男性不育有关。顺铂(顺二氨二氯铂(II),即CDDP)作为一种用于治疗多种癌症的化疗药物,据报道极有可能诱发睾丸毒性。给予抗氧化剂,如己酮可可碱(PTX),可能会减少CDDP的一些药物不良反应(ADR)。因此,本研究调查了PTX对成年雄性大鼠CDDP诱导的睾丸毒性的潜在保护作用。为此,将42只雄性大鼠随机分为7组。大鼠连续14天每天口服3种剂量(75、150和300 mg/kg)的PTX进行预处理。在研究的第14天,它们通过腹腔注射(IP)给予单剂量的CDDP(7 mg/kg)。最后,检测精子/睾丸参数、生殖激素的血清水平,包括睾酮、促黄体生成素(LH)和促卵泡生成素(FSH),这些是控制睾丸功能的关键内分泌因子,以及睾丸组织的组织病理学变化。75和150 mg/kg两种剂量的PTX预处理表明,CDDP给药后精子数量和活力显著增加。用300 mg/kg的PTX加CDDP治疗后,右侧和左侧睾丸重量明显下降。然而,75 mg/kg的PTX加CDDP显示出最接近正常的组织病理学特征。结果表明,单独使用PTX可提高一些参数,如精子数量,同时降低其他参数,包括精子快速运动能力和胚层厚度。此外,尽管睾酮或LH水平未受影响,但75和150 mg/kg剂量的PTX显著提高了平均血清FSH水平。得出的结论是,即使高剂量(如300 mg/kg)给予PTX也不能降低CDDP诱导的睾丸毒性,而75 mg/kg剂量的PTX似乎会部分增强CDDP的毒性作用。因此,在这方面需要进一步研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3327/5523557/c7b2169d5cde/tr-33-255f1.jpg

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