Egyptian Journal of Basic and Clinical Pharmacology

Egyptian Journal of Basic and Clinical Pharmacology
Vol. 7 (2017), Issue 2, pp. 56-69 
doi:10.32527/2017/101426

Cardamonin Attenuates Tamoxifen Induced Hepatotoxicity in Rats through Modulation of Inflammatory Mediators, Oxidative Stress and Apoptosis

Tamoxifen (TAM) is an anti-estrogen used in the prevention and treatment of hormone dependent breast cancer. TAM therapy may cause hepatic injury, which may indicate the stoppage of the drug. Therefore the present study was done to clarify the possible protective role of cardamonin (CAR) against TAM induced hepatotoxicity. In this work, the protective effects of CAR against TAM hepatotoxicity were studied in female rats. Sex groups of rats were used each formed of eight rats Group I (control group): received normal 0.5% carboxymethylcellulose vehicle orally for 7 weeks. Group II (CAR group): received CAR (30 mg/kg), orally suspended in 0.5% carboxymethylcellulose vehicle for 7 weeks .Group III (TAM 0.6 mg group): received tamoxifen in a dose of (0.6 mg /Kg/ day) for 6 weeks. Group IV: (TAM 0.6 mg & CAR group): TAM in a dose of (0.6mg /Kg/ day) orally for 6 weeks and CAR (30 mg/kg) orally, for 7 weeks. Group IV (TAM 45mg group): received TAM in a dose of (45 mg /Kg/ day) i.p., for 7 successive days. Groups VI (TAM 45mg& CAR group): TAM in a dose of (45 mg /Kg/ day) i.p., for 7 successive days and CAR (30 mg/kg) orally, for 2 weeks. TAM intoxication caused elevation of serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase, malondyde(MDA) and tumor necrosis factor – α (TNF α) as well as depletion of reduced glutathione(GSH) and superoxide dismutase (SOD)with degeneration and necrosis of the hepatocytes there was also decrease in serum concentrations of total cholesterol, HDL cholesterol , LDL cholesterol and triglyceride concentration compared to control group. Histopathological study revealed that CAR treatment resulted in marked improvement in histopathological and immunohistochemical pictures. Furthermore CAR treatment improves all biochemical markers compared TAM intoxicated group. In Conclusion, CAR supplementation appeared to be beneficial to a great extent in treating TAM hepatotoxicity.