Doxorubicin-induced Hepatorenal Dysfunctions in Wistar rats: Mechanistic Protective Role of Diosmin-Hesperidin Fixed-Dose Combinations Mediated via Oxidative and Inflammatory Stress Suppression

Background and Purpose: Doxorubicin (DOX), a widely used chemotherapeutic agent, is associated with severe off target hepatorenal toxicity due to oxidative stress, inflammation and apoptosis. This study investigated the possible protective effects of 50-200 mg/kg/day pretreatment of a fixed-dose combination of diosmin-hesperidin (DH) against DOX-induced hepatorenal toxicity in male Wistar rats. Methods: Forty-eight (48) young adult male Wistar rats were randomly allotted to 8 treatment groups of 6 rats per group and orally pretreated with DH at doses of 50, 100, and 200 mg/kg/day as well as 20 mg/kg/day silymarin (SIL), before DOX administration (3 mg/kg/i.p. route on alternate days), all for 10 days. Hepatic and renal function tests, oxidative stress markers [superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA), and reduced glutathione (GSH)], inflammatory markers [tumor necrosis factor-alpha (TNF-?) and interleukin-10 (IL-10)], and histopathological assessments were the measuring endpoints. Results: Biochemical analysis revealed that repeated treatment with DOX significantly (P