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

ABSTRACT Carbon tetrachloride (CCl 4 ) 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 CCl 4 ‐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. CCl 4 (liquid form, Sigma‐Aldrich) was diluted in olive oil to 30% (v/v) and administered intraperitoneally at 10 mL/kg once weekly. CCl 4 ‐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 CCl 4 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 CCl 4 ‐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.