Genistein Ameliorates Cyclophosphamide - Induced Hepatotoxicity by Modulation of Oxidative Stress and Inflammatory Mediators

• Published in: Open access Macedonian journal of medical sciences 2017-12, Vol.5 (7), p.836-843
• Main Authors: Mansour, Dina F, Saleh, Dalia O, Mostafa, Rasha E
• Format: Article
• Language: English
• Subjects: Basic Science
• ISSN: 1857-9655; 1857-9655
• DOI: 10.3889/oamjms.2017.093

The present study investigated the protective effect of the phytoestrogen, genistein (GEN), against (CP)-induced acute hepatotoxicity in rats. Male adult rats were randomly assigned into five groups. Normal control group received the vehicles; CP group received a single dose of CP (200 mg/kg, i.p). The other three groups received subcutaneous GEN at doses of 0.5, 1 and 2 mg/kg/day, respectively, for 15 consecutive days prior CP injection. Sera and liver tissues were collected forty-eight hours after CP injection for assessment of liver function enzymes (ALT and AST) in rat sera, the hepatic oxidative/nitrosative biomarkers (GSH, MDA and NOx), hepatic interleukin-1β, and myeloperoxidase activity. Immunohistochemistry of cyclooxygenase-2 and histopathological examination of liver tissues were also conducted. The CP-induced acute liver damage was evidenced by elevated serum ALT and AST accompanied by increased hepatic oxidative stress and inflammatory biomarkers. Immunohistochemical outcomes revealed hepatic cyclooxygenase-2 expression in CP group with distortion of liver architecture. GEN-pretreatment significantly ameliorated the deterioration of liver function and exerted significant anti-oxidant and anti-inflammatory activity with a marked decline in hepatic cyclooxygenase-2 expression in a dose dependent-manner. The present study demonstrated that the antioxidant and anti-inflammatory activities of GEN might contribute to its protective effects against CP-induced liver damage.