The effects of agmatine treatment on cisplatin-induced hepatotoxicity: an experimental rat study

Cisplatin is a widely used chemotherapeutic agent whose clinical utility is limited by dose-dependent hepatotoxicity, primarily driven by oxidative stress and inflammation. Agmatine, an endogenous polyamine, has demonstrated antioxidant and anti-inflammatory properties in various models; however, its hepatoprotective effects in cisplatin-induced liver injury remain underexplored.

This experimental study investigated the protective effects of agmatine against cisplatin-induced hepatotoxicity in 28 male Sprague Dawley rats. The animals were randomized into four groups: Sham, Cisplatin, Cisplatin + Agmatine (20 g/kg/day, orally), and Placebo. Biochemical markers, including ALT, AST, MDA (malondialdehyde), SOD (superoxide dismutase), GPx (glutathione peroxidase), TNF-α, IL-1β, and TGF-β, were assessed using ELISA (enzyme-linked immunosorbent assay). Histopathological evaluation was performed to assess liver architecture and injury severity.

Cisplatin administration significantly increased serum levels of ALT, AST, MDA, and proinflammatory cytokines (IL-1β, TNF-α, and TGF-β), while reducing antioxidant enzyme activities (SOD and GPx) (p < 0.01). Agmatine co-administration significantly reversed these biochemical alterations and ameliorated histopathological damage, as evidenced by reduced inflammatory infiltration, sinusoidal dilatation, and hepatocellular degeneration.

Agmatine demonstrates significant hepatoprotective effects against cisplatin-induced liver injury by attenuating oxidative stress and inflammatory responses. These findings suggest its potential role as an adjunctive agent to improve the hepatic safety profile of cisplatin chemotherapy.