Ellagic acid as a potential antioxidant, alleviates methotrexate-induced hepatotoxicity in male rats

Abstract

Background: Hepatotoxicity is one of the most life-threatening side-effects of Methotrexate therapy. Former studies highlighted the significance of oxidative stress in promoting Methotrexate-induced hepatotoxicity (MIH). Hence, the current study investigated the protective effect of Ellagic acid (EA), a poly-phenolic antioxidant, against MIH.

Methods: Twenty-eight male Wistar rats were grouped into four sets: group 1 (control), group 2 (injected intraperitoneally with 20 mg/kg of Methotrexate on the 9th day), group 3 (treated orally with 10 mg/kg/day of EA for 10 days and injected with Methotrexate on the 9th day) and group 4 (treated with EA for 10 days). Subsequently, biochemical and histopathological parameters were evaluated in serum samples and liver tissues.

Results: Methotrexate significantly increased activities of aminotransferases and ALP enzymes as well as levels of oxidative stress parameters in liver tissue. Likewise, Methotrexate decreased hepatic reduced glutathione level and activities of antioxidant enzymes. EA pre-treatment markedly attenuated the activities of aminotransferases and ALP, levels of oxidative stress parameters and augmented activities of antioxidant enzymes. Similarly, the remarkable protective effect of EA on liver has been confirmed by histological examination.

Conclusion: In sum, the current study supports the hypothesis that EA may be used as a promising pre-therapy to prevent the MIH.

Keywords:

• Methotrexate
• hepatotoxicity
• oxidative stress
• ellagic acid
• rat

Disclosure statement

The authors confirm that there are no conflicts of interest.

Additional information

Funding

This study was supported by 94s131 provided by Deputy of Research of Ahvaz, Jundishapur University of Medical Sciences, Ahvaz, Iran.