The role of antioxidant (vit-A and glutamine) in ameliorating methotrexate induced hepatic toxicity in rats

Abstract

The aim of this study was to investigate the status of antioxidant glutathione peroxidase (GSH-Px) during oxidative stress in blood serum of rats subjected to oral methotrexate administration at a dose 10 mg/kg B.W and administrated antioxidant therapy (vit A and glutamine) to reduced or ameliorate such stress. A total of thirty six, male Sprague-Dawley rats weighing (250 – 300) g divided equally into six groups. The first group, control, were fed only standard rat chow as their diet and water ad libitum. The second group administered orally a single dose of methotrexate at a dose of 10 mg/kg B.W. The third group, given a single dose of methotrexate 10 mg/kg B.W + Vit-A (5000 IU/kg B.W) orally by stomach tube, twice daily. The fourth group, given a single dose of methotrexate 10 mg/kg B.W + Glutamine (500 mg/kg B.W), twice daily dosing. fifth group, given vit-A at dose 5000 IU/kg B.W orally, twice daily. Sixth group, given glutamate at dose 500 mg/BW orally, twice daily, all this dosing continue for 8 days. At the end from all animal, draw blood from heart by syring to obtained serum to determine its level then sacrificed and take section from liver for histopathology resulted in. It was found that methotrexate caused a signifcant increase in GSH levels (an important marker of lipid peroxidation) when compared with the control group while the level GSH were signifcantly decreased in the methotrexate + vitamin A group, methotrexate+ glutamine group, vitamin A group and glutamine group. The results indicate that methotrexate cause oxidative stress by reducing the activities and consequently the effectiveness of the antioxidant enzyme defense system. while the antioxidant therapy reducing of oxidative stress. Histopathological examination observed was normal in methotrexate treated rats and MTX with glutamine and vitmine A . but showed hydrodegenerate in treated groups of MTX+vit A while the glutamine treated group showed a necrosis and amyliod change.