Rice bran phytic acid protects against methotrexate -induced oxidative stress and acute liver injury in rats

Abstract

Methotrexate is an effective and extensively used chemotherapeutic agent to treat range of malignancies, but its therapeutic use is limited because of dose dependent hepatotoxicity. Several published reports advocate that supplementation with antioxidant can influence methotrexate induced acute liver injury. Twenty four adult male rats (aged 56 days and weighted 138±8.8g) were randomly assigned into four equal groups (control and three treated groups), first group as control group given normal saline, a second single injection 20mg /kg B.W. i.p. of methotrexate, third group given15mg/kg B.W. of phytic acid, then given single injection 20mg /kg B.W. i.p. of methotrexate and fourth group given 15mg/kg B.W. of phytic acid for 10 days, and male rats were sacrificed. Blood and liver, subcellular fluid was obtained to assess subcellular activity of Alanine aminotranferease (ALT), Aspartate aminotransferase (AST), reduced glutathione (GSH), glutathione reductase, glutathione-S-transferase (GST), glutathione peroxidase (GPx), catalase, quinone reductase (QR), superoxide dismutase (SOD), γ-glutamyl transpeptidase (GGT), lactate dehydrogenase (LDH), lipid peroxidation, glucose-6-phosphate dehydrogenase (G6PD) and total protein. The results of liver injury rats (T) showed significant increased activity of ALT, AST, GGT, LDH, decreased GSH, GR, GST, GPx, CAT, QR, SOD, (p<0.05) when compared with the control, and histological findings further supported the protective effects of phytic acid against methotrexate induced acute liver injury. phytic acid (D) therapy moderated liver damage and normalized the activities of all antioxidant enzymes. In conclusion, present study demonstrate that oxidative stress and liver injury are closely associated with methotrexate induced toxicity and phytic acid shows the protective efficacy against methotrexate induced acute liver injury possibly via attenuating the oxidative stress and inflammatory response.