Abstract
BACKGROUND AND AIM: Cisplatin, a platinum-based chemotherapeutic agent, is widely employed in the treatment of various malignancies. However, its clinical utility is restricted by dose-limiting hepatorenal toxicities, primarily driven by oxidative stress, inflammation, and direct cytotoxicity. The present in vivo study was designed to evaluate the protective efficacy of Bacopa monnieri extract against cisplatin-induced hepatorenal toxicity in male Wistar rats, utilizing biochemical parameters, oxidative stress biomarkers, histopathological assessment, and the early renal injury marker Kidney Injury Molecule-1 (KIM-1). MATERIALS AND METHODS: Thirty male Wistar rats were randomly divided into five groups (n = 6 per group): control (normal saline), cisplatin (7.5 mg/kg intraperitoneally on day 7), and three intervention groups receiving B. monnieri (BM) extract orally at 100, 200, or 300 mg/kg daily for 10 consecutive days concomitantly with cisplatin. Urine samples were collected on day 9 for KIM-1 quantification. On day 11, animals were euthanized, and blood, liver, and kidney tissues were obtained for biochemical assays (liver and kidney function tests, malondialdehyde, glutathione, superoxide dismutase, catalase) and histopathological evaluation. RESULTS: Administration of BM at 200 and 300 mg/kg significantly attenuated cisplatin-induced elevations in serum alkaline phosphatase, aspartate aminotransferase, and alanine aminotransferase (all p < 0.001 versus the cisplatin group). Total protein and albumin levels were restored toward control values in the 300 mg/kg group. Urea concentrations decreased significantly at 300 mg/kg, while creatinine levels were reduced at both 200 and 300 mg/kg doses (p < 0.001). Urinary KIM-1 concentrations remained elevated in all cisplatin-exposed groups without significant mitigation by BM. Dose-dependent improvements in antioxidant status were observed, with increased glutathione, superoxide dismutase, and catalase activities and decreased malondialdehyde levels in both liver and kidney tissues (p < 0.001 at higher doses). These biochemical findings were strongly supported by histopathological evidence showing reduced inflammatory cell infiltration, tubular necrosis, hydropic degeneration, sinusoidal dilatation, and fatty change, with near-normal tissue architecture restored at the 300 mg/kg dose. CONCLUSION: BM extract confers significant, dose-dependent hepatorenal protection against cisplatin-induced toxicity, predominantly through its potent antioxidant mechanisms, with maximal efficacy at 300 mg/kg. However, it failed to prevent early proximal tubular injury as reflected by persistent KIM-1 elevation. These results position BM as a promising adjunctive agent in cisplatin-based chemotherapy regimens and justify further mechanistic and clinical translational studies.