Effects of Omega-3 and Vitamin C on Methotrexate-Induced Liver Injury

Abstract

Context: Methotrexate (MTX)-induced liver injury is a serious side effect characterized by the increased level of hepatic biomarkers and resulted in acute liver failure. Omega 3 and Vitamin C act as antioxidant that participate in the fighting of free radicals generation during the inflammatory process. Aims: To evaluate the effect of omega 3 and Vitamin C on hepatotoxicity induced by MTX. Settings and Design: 42 (Swiss albino mice) used and divided into six groups (7 mice each): First: Maintained with normal saline, second: Received a single dose injection of MTX (20 mg/kg, intraperitoneally), third: Pretreated with omega 3 100 mg/kg, fourth: Pretreated with omega 3 200 mg/kg, fifth: Pretreated with Vitamin C 100 mg/kg, sixth: Pretreated with Vitamin C 200 mg/kg, then these group injected with MTX on day 10. Subjects and Methods: MTX as 50 mg injection. Omega 3 as capsule 1000 mg. Vitamin C as powder 1000 mg. Assessment of liver enzymes (alanine aminotransferase [ALT], aspartate aminotransferase [AST], and alkaline phosphatase [ALP]) made using automated computering device (Flexor–EL80) provider by Vitalab (South Africa). Assessment of oxidative stress markers (malondialdehyde [MDA], superoxide dismutase [SOD], reduced glutathione [GSH]) and lactate dehydrogenase (LDH) made by using competitive ELISA kits using (ELISA microplate Humareader). Results: This study showed a significant increase in the liver enzymes (ALT, AST, ALP, and LDH) as well oxidative stress markers (MDA, SOD, and GSH) with severe changes in the histopathological findings (severe inflammatory cell necrosis) among group injected with MTX as compared with control group and illustrated improvement in serum level of ALT, ALP, LDH, MDA, SOD and reduced GSH; besides improved histopathological findings (mild and moderate changes) for a group of mice pretreated with omega 3 and Vitamin C. Conclusions: This study concluded that pretreatment with omega 3 (which was strong antioxidant supplement) and Vitamin C (which was dose-dependent manner with beneficial antioxidant action) exert more hepatoprotective effect against oxidative tissue damage induced by MTX.