Ginseng Protects Against Cisplatin-Induced Liver Failure by Regulating Drug-Metabolizing Enzymes

Abstract

<ns3:p>Background Cisplatin is a widely used chemotherapeutic agent; however, its clinical application is limited by severe adverse effects, including hepatotoxicity. Natural antioxidants may offer protective strategies against such toxicity. Methods Male rats were treated intraperitoneally with cisplatin (4 mg/kg body weight/week) for three months to induce hepatotoxicity. Ginseng was administered orally at a dose of 100 mg/kg body weight/day. Hepatic drug-metabolizing enzymes, gene expression of phase I enzymes, inflammatory mediators, oxidative stress markers, apoptotic factors, and histopathological alterations were evaluated. Results Cisplatin administration markedly impaired hepatic drug-metabolizing enzymes, including cytochrome P450, cytochrome b5, amidopyrine N-demethylase, aniline 4-hydroxylase, and NADPH cytochrome-c reductase. It also significantly altered the gene expression of cytochrome P1A1, cytochrome P2E1, cytochrome P2D6, and cytochrome P3A4. In addition, cisplatin increased hepatic tumor necrosis factor-alpha, interleukin-6, cyclooxygenase-2, transforming growth factor-beta, nuclear factor kappa-B, p53, and caspase-3. Histological and histochemical analyses confirmed severe hepatic damage. Co-administration of ginseng significantly attenuated these biochemical, molecular, and histopathological alterations. Conclusions Ginseng exerts a protective effect against cisplatin-induced hepatotoxicity by restoring hepatic drug-metabolizing enzymes and reducing oxidative stress, inflammation, and apoptosis.</ns3:p>