Modulation of brain antioxidant enzymes by methotrexate administration in animal model.

Abstract

Reactive oxygen species (ROS), when overproduced in a biological system can interact very rapidly with most biological molecules with usually harmful consequences. ROS initiate the process of degradation of polyunsaturated fatty acids referred to as lipid peroxidation. It has been proven that reactive oxygen species/free radicals are involved in many pathological processes in humans and animals. The present study was initiated in order to investigate methotrexate (MTX)-induced oxidative stress and its modulatory effect on antioxidant enzyme and thiobarbituric acid reactive substance (TBARS) status in an animal model. Twenty-one male Wistar rats (aged 6-8 weeks) weighing averagely 171.7 g were randomly divided into three groups with 7 rats in a group. MTX was diluted with appropriate volume of distilled water to obtain desired concentration. The animals were orally administered MTX in the following pattern: group 1: control rats received standard rat diet and water; group 2: MTX-treated rats (13.4 mg/kg body weight/week, for 3 weeks) and group 3: MTX-treated rats (13.4 mg/kg body weight /week for 6 weeks). At the end of the feeding period, the animals were sacrificed, brain removed and immediately cleaned with ice cold saline and transferred to ice chamber. Selected biomarkers were determined according to standard biochemical procedures. The activities of catalase (CAT), superoxide dismutase (SOD) and glutathione reductase (GR) did not differ significantly from the control group after 3 weeks of oral administration of MTX. However, these same enzymes were significantly altered after 6 weeks of MTX administration and with a significant increase in the level of TBARS indicating that MTX demonstrated adverse effects on antioxidant enzymes in rat brain homogenate.