Cola hispida Leaf Extract Attenuates Carbon Tetrachloride-Induced Hepato-Reno-Hematotoxicity via Antioxidant Modulation in Rats.

Carbon tetrachloride (CCl4) induces oxidative stress, leading to liver, kidney, and hematological toxicity. Cola hispida, a plant with ethnomedicinal relevance, possesses bioactive compounds with potential antioxidant properties. This study investigates the protective effects of the methanolic extract of C. hispida (MECH) against CCl4-induced systemic toxicity in rats. Thirty rats were randomly assigned to six groups: controls, CCl4-only, and co-treatment with MECH at doses of 100, 300, and 600 mg/kg for 21 days, as well as the MECH-only group. CCl4 (liquid form, Sigma-Aldrich) was diluted in olive oil to 30% (v/v) and administered intraperitoneally at 10 mL/kg once weekly. CCl4-induced organ toxicity was assessed via changes in body and organ weights, liver and kidney function markers, hematological indices, malondialdehyde (MDA), oxidative stress biomarkers [superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), glutathione peroxidase (GPx)], and histopathology. The administration of CCl4 caused a significant (p < 0.001) increase in hepatic and renal indices [Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP), urea, creatinine, sodium], oxidative stress (elevated malondialdehyde [MDA]), and hematological disturbances [significant decrease in packed cell volume (PCV), red blood cell count (RBC), hemoglobin (Hb), and increased erythrocyte sedimentation rate (ESR) and white blood cell count (WBC)]. The methanolic extract of C. hispida (MECH) co-administration dose-dependently reversed these alterations. Antioxidant enzymes were significantly restored, and histopathological evaluation confirmed reduced tissue damage in the MECH-treated groups. Correlation and Principal Component Analysis (PCA) revealed strong inverse relationships between oxidative stress markers and organ function parameters. MECH exhibits potent systemic protective effects against CCl4-induced hepato-renal and hematological damage, primarily through antioxidant and anti-inflammatory mechanisms. These findings underscore the therapeutic promise of C. hispida in the management of oxidative stress-related multi-organ toxicity and support its ethnopharmacological use.