Ellagic Acid Protects Multiple Organ Injury Induced by Cyclophosphamide‐Mediated Oxidative Stress: Biochemical and Histological Insights

Cyclophosphamide, a commonly used alkylating chemotherapeutic, induces acute multiple organ injury through oxidative stress, inflammation, and redox imbalance. The present study identifies oxidative signalling as a key mechanism of cyclophosphamide-mediated liver, kidney, and brain injury and evaluates dose-dependent protective effects of ellagic acid, a natural dietary polyphenol. Male Wistar rats were orally pretreated with ellagic acid (10, 20, 30, and 40 mg/kg) for 6 days before receiving a single intraperitoneal dose of cyclophosphamide (200 mg/kg) on Day 6 to reliably induce multiple organ injury within 24 h. Animals were euthanized 24 h after administration of the last dose of cyclophosphamide for serological, tissue biochemical, and histological assessments. Cyclophosphamide significantly altered liver and kidney function markers, increased lipid peroxidation, and depleted antioxidant enzyme activities, confirming oxidative stress-driven injury. Severe deformities in the tissue architecture of liver, kidney, and brain were also evident after exposure to cyclophosphamide. Ellagic acid markedly restored antioxidant defense system, normalized biochemical indices, and preserved tissue integrity in a dose-dependent manner. These findings revealed mechanistic interplay between oxidative stress and systemic injury and demonstrated that ellagic acid effectively mitigates adverse effects of cyclophosphamide-induced multiple organ injury.