Abstract
BACKGROUND: Doxorubicin (DOX), a common chemotherapeutic agent, is often associated with dose-limiting hepatotoxicity. Alamandine, a peptide of the renin-angiotensin system, has shown antioxidant and anti-inflammatory properties that may counteract these adverse effects. OBJECTIVE: This study investigated the protective effects of alamandine on DOX-induced liver injury in rats. METHODS: Male Wistar rats received DOX (3.75 mg/kg intraperitoneally) on days 14, 21, 28, and 35, reaching a cumulative dose of 15 mg/kg. Alamandine (50 µg/kg/day) was administered continuously via mini-osmotic pumps for 42 days. Liver toxicity was assessed through biochemical measurements of oxidative stress markers, inflammatory cytokines, and liver enzymes, as well as histological examination. RESULTS: DOX administration significantly increased serum alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), and malondialdehyde (MDA) levels while reducing superoxide dismutase (SOD) and catalase (CAT) activity. Histological analysis revealed hydropic degeneration and hepatocyte necrosis. Alamandine co-treatment restored SOD and CAT activity, reduced MDA and inflammatory markers, and normalized liver enzyme levels, indicating significant hepatoprotection. Furthermore, treatment with alamandine reduced the expression of pro-inflammatory cytokines IL-6, IL-1, and NF-κB induced by DOX, while p53 expression remained unchanged. CONCLUSION: Alamandine effectively mitigates DOX-induced hepatotoxicity, demonstrating its therapeutic potential as an adjunctive agent in chemotherapy through its antioxidant and anti-inflammatory mechanisms.