Diosmin-Hesperidin fixed-dose combination ameliorates cisplatin-induced hepotorenal toxicities in wistar rats: Involvements of antioxidant and anti-inflammatory mechanisms

The chemotherapeutic agent, cisplatin (CIS), is limited by significant hepatorenal toxicity. This study evaluated the protective efficacy of a micronized diosmin (90 %) and hesperidin (10 %) combination (DH) against this toxicity in young adult male Wistar rats. In a dose-response study, rats were orally pre-treated with DH (50, 100, and 200 mg/kg/day) for 10 days before receiving CIS. Control groups received distilled water, CIS alone, DH alone, or silymarin (SIL) as a positive control. Following euthanasia and sacrifice, serum and tissue samples were analyzed for biochemical markers of liver and kidney function, oxidative stress (SOD, CAT, MDA, GSH), and inflammation (TNF-α, IL-10), along with histopathological assessments.Results showed that cisplatin administration induced significant hepatorenal dysfunction, oxidative imbalance, and inflammatory responses (p < 0.05, p < 0.0001 versus control). However, DH pre-treatment provided a dose-dependent protective effect, significantly attenuating these adverse changes, preserving tissue integrity, and improving biochemical indices of oxidative stress and inflammation (p < 0.05, p < 0.0001 versus CIS alone). These results provide compelling preclinical evidence for the capacity of a diosmin-hesperidin combination to mitigate CIS-induced hepatotoxicity and nephrotoxicity. The primary mechanism of this protection appears to involve the synergistic modulation of oxidative stress and inflammatory pathways. As this specific micronized flavonoid formulation is already an approved clinical agent with a well-established safety profile for its venotonic and vasoprotective effects, these findings support its potential for drug repositioning. It represents a promising candidate for off-label use as an adjunctive therapy to ameliorate debilitating side effects, potentially improving therapeutic outcomes and patient quality of life during cisplatin-based chemotherapy.