Diosmin and Coenzyme q10: Synergistic histopathological and functional protection against doxorubicin-induced hepatorenal injury in rats.

Abstract

Doxorubicin (DOX) is a cytotoxic anthracycline used to treat a variety of cancers. Cardiotoxicity, hepatotoxicity, and nephrotoxicity are adverse effects of DOX, that limit prognosis. The study aims to determine if diosmin (DIOS) and coenzyme Q10 (CoQ10) alone or in combination protect rats against DOX-induced liver and kidney damage. Adult male rats were assigned randomly in five groups. An intraperitoneal injection of DOX (2.5 mg/kg) was given to the DOX group every other day for three weeks, whereas a normal control group received the vehicle. Diosmin group received oral DIOS (100 mg/kg), Co-Q10 group received oral CoQ10 (10 mg/kg) and combination group received oral DIOS and CoQ10 daily for three weeks concomitantly with DOX. Sera and tissues were obtained 24 hours after last DOX injection. Serum aspartate transaminase (AST), alanine transaminase (ALT), creatinine, urea, total bilirubin and direct bilirubin were detected with hepatic and renal reduced glutathione (GSH), malondialdehyde (MDA), tumor necrosis factor-alpha (TNF-α) and nuclear factor kappa-B (NF-κB). Histopathology and morphometry of liver and kidney were assessed. DOX exerted significant hepatorenal toxicity via elevation of liver and kidney functions, inducing oxidative stress by reducing GSH and elevating MDA, triggering renal and hepatic TNF-α and NF-kB. DIOS and CoQ10 modulated hepatic and renal functions, oxidative stress and inflammatory biomarkers. DIOS-CoQ10 combination treatment showed significant improvement in histopathology of liver and kidney along with morphometry compared to DOX group. In conclusion, combining DIOS and CoQ10 exhibited synergistic protective activity against DOX-induced hepatic and renal insult via their antioxidant and anti-inflammatory properties.