Department of Histology and Embryology, Faculty of Medicine, Harran University, Sanlıurfa, Turkey.
Department of Histology and Embryology, Faculty of Medicine, Yozgat Bozok University, Yozgat, Turkey.
Hum Exp Toxicol. 2020 Oct;39(10):1364-1373. doi: 10.1177/0960327120924108. Epub 2020 May 12.
Doxorubicin (DOX) is used for treatment of many cancer types. Thymoquinone (THQ) is a powerful antioxidant agent used for reducing side effects of several drugs. The aim of this study is to determine possible therapeutic effects of THQ on doxorubicin-induced testicular toxicity in rats.
Rats were divided into five groups ( = 8): control, THQ, olive oil, DOX (a single dose of 15 mg/kg intraperitoneally (i.p.) on seventh day of the experiment), and DOX + THQ (10 mg/kg THQ per day and 15 mg/kg DOX i.p. on seventh day). Animals were euthanized, and testis tissues were evaluated histopathologically. Caspase 3 and HSP90 immunostaining were performed to determine the expression levels of these proteins among groups. Terminal deoxynucleotidyl transferase 2'-deoxyuridine, 5'-triphosphate nick-end labeling method was used for evaluation of apoptotic index. Moreover, serum testosterone levels and total antioxidant status (TAS) and total oxidant status (TOS) in testicular tissue were measured by ELISA assay.
The DOX group had histopathological deterioration compared to the control group. There was an increase in apoptotic index, caspase 3 and HSP90 expressions in the DOX group. While TAS level of the DOX group decreased, TOS level increased when compared with the other groups. Serum testosterone levels in the DOX group decreased compared to the control group. However, there was improvement in testicular tissue in DOX + THQ group compared to the DOX group. There was a decrease in apoptotic index, caspase 3, and HSP90 expressions in DOX + THQ group compared to the DOX group. Testosterone level of DOX + THQ significantly increased compared to the DOX group.
We suggest that THQ can be used as a protective agent to reduce the toxic effects of DOX.
阿霉素(DOX)用于治疗多种癌症类型。百里醌(THQ)是一种强大的抗氧化剂,用于减少几种药物的副作用。本研究旨在确定 THQ 对大鼠阿霉素诱导的睾丸毒性的可能治疗作用。
将大鼠分为五组(n=8):对照组、THQ 组、橄榄油组、DOX 组(实验第 7 天腹腔内给予 15mg/kg DOX 单次剂量)和 DOX+THQ 组(第 7 天每天给予 10mg/kg THQ 和 15mg/kg DOX 腹腔内注射)。处死动物,评估睾丸组织的组织病理学。进行 caspase 3 和 HSP90 免疫染色,以确定各组中这些蛋白的表达水平。末端脱氧核苷酸转移酶 2'-脱氧尿苷,5'-三磷酸末端标记法用于评估细胞凋亡指数。此外,通过 ELISA 测定睾丸组织中的血清睾酮水平以及总抗氧化状态(TAS)和总氧化状态(TOS)。
与对照组相比,DOX 组的组织病理学恶化。DOX 组的细胞凋亡指数、caspase 3 和 HSP90 表达增加。与其他组相比,DOX 组的 TAS 水平降低,TOS 水平升高。与对照组相比,DOX 组的血清睾酮水平降低。然而,与 DOX 组相比,DOX+THQ 组睾丸组织得到改善。与 DOX 组相比,DOX+THQ 组的细胞凋亡指数、caspase 3 和 HSP90 表达减少。与 DOX 组相比,DOX+THQ 组的睾酮水平显著升高。
我们认为 THQ 可用作保护剂,以减少 DOX 的毒性作用。