El-Sheikh Azza A K, Morsy Mohamed A, Mahmoud Marwa M, Rifaai Rehab A
Department of Pharmacology, Faculty of Medicine, Minia University, El-Minia, Egypt.
Department of Pharmacology, Faculty of Medicine, Minia University, El-Minia, Egypt.
Environ Toxicol Pharmacol. 2014 Mar;37(2):772-81. doi: 10.1016/j.etap.2014.02.010. Epub 2014 Feb 19.
The anticancer drug; doxorubicin (DOX), causes testicular toxicity as an adverse effect. P-glycoprotein (P-gp) is a multidrug resistance efflux transporter expressed in blood-testis barrier, which extrudes DOX from the testis. We investigated whether DOX-induced gonadal injury could be prevented by the use of antioxidant; coenzyme-Q10 (CoQ10). The involvement of P-gp expression, as a possible protective mechanism, was also investigated. CoQ10 was administered orally for 8 days, and DOX toxicity was induced via a single i.p. dose of 15 mg/kg at day 4. Concomitant administration of CoQ10 with DOX significantly restored testicular oxidative stress parameters and the distorted histopathological picture, reduced the up-regulation of caspase 3 caused by DOX, and increased P-gp expression. We show for the first time that CoQ10 up-regulates P-gp as a novel mechanism for gonadal protection. In conclusion, CoQ10 protects against DOX-induced testicular toxicity in rats via ameliorating oxidative stress, reducing apoptosis and up-regulating testicular P-gp.
抗癌药物阿霉素（DOX）会产生睾丸毒性这一副作用。P-糖蛋白（P-gp）是一种在血睾屏障中表达的多药耐药外排转运蛋白，它能将DOX从睾丸中排出。我们研究了使用抗氧化剂辅酶Q10（CoQ10）是否可以预防DOX诱导的性腺损伤。同时还研究了P-gp表达作为一种可能的保护机制所起的作用。CoQ10口服给药8天，在第4天通过腹腔注射15mg/kg的单次剂量诱导DOX毒性。CoQ10与DOX联合给药可显著恢复睾丸氧化应激参数和扭曲的组织病理学图像，减少DOX引起的半胱天冬酶3上调，并增加P-gp表达。我们首次表明CoQ10上调P-gp是一种新的性腺保护机制。总之，CoQ10通过改善氧化应激、减少细胞凋亡和上调睾丸P-gp来保护大鼠免受DOX诱导的睾丸毒性。
