Protective mechanisms of coenzyme-Q10 may involve up-regulation of testicular P-glycoprotein in doxorubicin-induced toxicity

• CoQ10 has a testicular protective effect against DOX-induced toxicity.
• CoQ10 reverses DOX-induced oxidative and nitrosative stress plus its apoptotic effect.
• DOX up-regulates P-gp, the efflux transporter, as an endogenous defensive mechanism.
• Co-administering CoQ10 further increases testicular expression of P-gp.
• This expression presenting a novel mechanism of CoQ10-mediated gonadal protection.

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.