Hepatoprotective Effects of Pomegranate Against Methotrexate-Induced Acute Liver Injury

Abstract

Background: Methotrexate (MTX) is a synthetic antimetabolite with a wide range of clinical applications, but its liver toxicity induced mainly through oxidative stress represents a primary concern on its clinical use. Pomegranate fruit contains many polyphenolic compounds that possess potent antioxidant effects and, therefore, have a possible hepatoprotective effect. Objectives: This study seeks to address the hepatoprotective effects of pomegranate against MTX-induced liver injury. Materials and Methods: Twenty-eight healthy female albino mice were grouped into four groups; control and MTX groups received oral 0.5 ml distilled water, while; the PG150 group received 150mg/kg oral pomegranate, and the PG300 group received 300mg/kg oral pomegranate. The oral course continues for 10 days, and on the last day, all groups were injected with 20 mg/kg MTX intraperitoneally, except the control group injected with normal saline. 48-hours later, samples were collected and prepared for biochemical and histopathological evaluation. Results: After biochemical analysis, MTX causes an elevation in serum Alanine aminotransferase, Lactate dehydrogenase, and liver tissue malondialdehyde, indicating hepatic injury, while pomegranate pre-treatment will hold down this elevation significantly and dose-dependently, causing amelioration of the toxic effect of MTX; the histopathological findings support this finding. Also, MTX causes consumption of liver tissue content of superoxide dismutase (SOD) and Glutathione (GSH), while pomegranate pre-treatment boosts the SOD and GSH hepatic tissue level. Conclusion: Pomegranate has a dose-dependent amelioration effect on the toxic effect of MTX on the liver.