Effect of Ellagic Acid on Tamoxifen-Induced Hepatotoxicity in Rats

Hawbash Hussein, Hiewa Dyary and Salam Ibrahim

Background and Objective: Hepatotoxicity occurs as one of the adverse effects of tamoxifen (TAM), an antiestrogen compound used to treat and prevent all stages of estrogen-dependent breast cancer. It is thought that antioxidant agents could ameliorate TAM’s hepatotoxic effect in these patients. In this study, the ellagic acid (EA), an antioxidant compound, was tested for its effect on hepatotoxicity caused by TAM. Materials and Methods: Forty-eight female albino Wistar rats were allocated into eight control and treatment groups. After treatment for nine consecutive days, serum samples were collected for serological tests, while liver tissues were collected for histopathological analysis. The body and liver weights were measured to determine their correlation ratio. A one-way analysis of variance was used to compare the data statistically. Results: The EA-treated groups showed a significant reduction in the values of Alanine Transaminase (ALT), Alkaline Phosphatase (ALP), Aspartate Transaminase (AST), Lipid Peroxide (LPO) and Hydrogen Peroxide (H₂O₂), with increasing concentrations of Reduced Glutathione (GSH). A statistically significant (p<0.05) reduction was found in the EA-treated groups regarding the liver-to-body weight ratio. Moreover, histopathological findings indicated that EA treatments reduced the hepatotoxicity lesions in the liver tissues, such as massive hemorrhage in the subcapsular area/liver parenchyma, severe steatohepatitis, ballooning degeneration of hepatocytes and marked infiltration of polymorphonuclear inflammatory cells in centrilobular/portal area. Conclusion: The oral EA treatments at various doses could ameliorate the hepatotoxicity induced through TAM injection in female albino Wistar rats. Thus, supplementation of EA could help alleviate liver injury induced by TAM treatment.

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