Multi-organ protective role of ellagic acid-selenium nanoparticles against cyclophosphamide-mediated oxidative damage: biochemical and histological insights.

Abstract

OBJECTIVES: Cyclophosphamide induces severe oxidative stress-mediated multi-organ toxicity, limiting its therapeutic application. The present study evaluated the protective effects of ellagic acid-selenium nanoparticles against cyclophosphamide-induced injury to liver, kidney, and brain. METHODS: Male Wistar rats were pretreated orally with ellagic acid-selenium nanoparticles at doses of 1, 2, 3, and 4 mg/kg for six consecutive days followed by a single intraperitoneal administration of cyclophosphamide at 200 mg/kg on Day 6. Body and organ weights, oxidative stress markers, antioxidant enzymes, microsomal enzyme activity, biochemical and neurochemical parameters, and histopathological alterations were assessed. KEY FINDINGS: Cyclophosphamide exposure markedly increased lipid peroxidation and significantly reduced glutathione, superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glutathione-S-transferase, and glucose-6-phosphate dehydrogenase activities. Altered microsomal enzyme activity, elevated liver and kidney function markers, dyslipidaemia, increased acetylcholinesterase and butyrylcholinesterase activities, reduction in body weight, altered relative organ weights, and severe histopathological damage in liver, kidney, and brain tissues were also observed. Pretreatment with ellagic acid-selenium nanoparticles significantly restored antioxidant defence systems, normalized biochemical and neurochemical alterations, and preserved tissue architecture in a dose-dependent manner. CONCLUSIONS: Ellagic acid-selenium nanoparticles demonstrated substantial multi-organ protective effects against cyclophosphamide-induced oxidative injury and may represent a promising adjunctive nanomedicine strategy for reducing chemotherapy-associated systemic toxicity.

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