Effect of d-amphetamine repeated administration on rat antioxidant defences

The purpose of this study was to evaluate rat tissue antioxidant status aft er repeated administration of d-amphetamine. Three groups of four rats each were used: control, d-amphetamine sulphate dosed (s.c., 20 mg/kg per day), and pair-fed. After 14 days of ii-amphetamine daily administration, supero xide dismutase (CuZnSOD and MnSOD), catalase, glutathione peroxidase (GPx), glutathione reductase (GRed), glutathione-S-transferase (GST), glutathione (GSH), cysteine and thiobarbituric acid reactive substances (TBARS) were m easured in liver, kidney, and heart. Various serum and urine parameters wer e also analysed. ci-Amphetamine treatment induced an increase of liver GSH, as well as a decrease of cysteine and MnSOD levels in this organ. A small increase in serum transaminases was also observed in comparison to the pair -fed group. Hepatic levels of TEARS, GPx, GRed and CuZnSOD were found to be similar among the three groups of rats. d-Amphetamine treatment induced an increase of kidney GST, GRed and catalase levels, and an elevation of N-ac etyl-beta-D-glucosaminidase efflux to the urine, accompanied by a decrease in urinary creatinine, compared to the pair-fed group. In cl-amphetamine tr eated animals, heart cysteine levels were significantly depleted when compa red to the pair-fed group, but all three groups of rats were found to have similar heart antioxidant enzyme levels. These results indicate that repeat ed administration of ti-amphetamine caused a certain degree of stress in li ver and kidney, which was followed by adaptations of antioxidant defences. The mechanisms involved in d-amphetamine-induced toxicity may explain the d ifferent adaptations observed for the studied organs.