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Background: Hepatotoxicity—the most important side effect of the Methotrexate (MTX)—seems to relate to the generation of reactive oxygen species. Pomegranate has high anti-oxidant capacities. We studied if MTX-induced hepatotoxicity can be protected by pomegranate peel and seed methanolic extracts (PPE and PSE) in rats. Methods: Forty-eight Wistar rats were divided on the basis of: orally received normal saline as control, orally received 500 mg/kg PSE, orally received 500 mg/kg PPE, intramuscularly (IM) received 10 mg/kg MTX, MTX- and PSE-received, and MTX- and PPE-received groups. After the intervention, blood and liver samples were obtained. Results: The results showed considerable antioxidant activity (510.7 ± 2.5 µg/ml) and total phenolic content (147.2 ± 0.2 mg GAE/g extract) of PSE and PPE, respectively. The ALT value reached the levels of the control group after treatment with PSE in PSE + MTX group. The serum level of ALT showed a significant increase in PPE+MTX group in comparison with MTX group. The results indicated that the PSE and PPE did not have considerable effect on ALP levels alone or together with MTX. Our results showed that PSE+ MTX and also PPE+ MTX treatment caused serum AST values to increase significantly in comparison with control and MTX groups. In histopatological study, the extracts decreased the pathological changes induced by methotrexate. Conclusion: The present study demonstrated that PPE and PSE that have notable total flavonoid and phenolic contents and also antioxidant activity, can protect the liver against histo-pathological and some enzymatic changes induced by MTX in rats.

Effects of Pomegranate Seed and Peel Methanolic Extracts on Methotrexate-Induced Hepatotoxicity in Rats