Methamphetamine-induced changes in antioxidant enzymes and lipid peroxidation in copper/zinc-superoxide dismutase transgenic mice.
The present study was conducted to investigate the effects of methamphetamine (METH)-induced toxicity on brain cortical and striatal antioxidant defense systems. Because METH-induced toxicity is attenuated in copper/zinc-superoxide dismutase transgenic (Cu/Zn-SOD-Tg) mice, we sought to determine if METH had differential effect on antioxidant enzymes on these mice in comparison to non-Tg mice. METH (4 x 1) mg/kg) induced a significant decrease in Cu/Zn-SOD activity in the cortical region without altering striatal enzymatic activity in non-Tg mice; whereas homozygous SOD-Tg mice showed a significant increase in the striatum. In addition, METH caused decrease in catalase (CAT) activity in the striatum of non-Tg mice and significant increase in the cortex of homozygous SOD-Tg mice. METH also induced decreases in glutathione peroxidase (GSH-Px) in both cortical and striatal regions of non-Tg mice and in the striatum of heterozygous SOD-Tg mice. Lipid peroxidation was increased in both cortices and striata of non-Tg and heterozygous SOD-Tg, mice, whereas the homozygous SOD-Tg mice were not affected. These results are discussed in terms of their substantiation of a role for oxygen-based radicals in METH-induced toxicity in rodents.
Jayanthi
S
S
Molecular Neuropsychiatry Section, National Institute of Drug Abuse (NIDA), National Institutes of Health (NIH), Baltimore, Maryland 21224, USA.
Ladenheim
B
B
Cadet
J L
JL
D000818:Animals; D002374:Catalase / Q000378:metabolism; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D015259:Dopamine Agents / Q000506:poisoning*; D005625:Frontal Lobe / Q000187:drug effects / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D006579:Heterozygote; D006720:Homozygote; D008054:Lipid Peroxides / Q000378:metabolism*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008694:Methamphetamine / Q000506:poisoning*; D051379:Mice; D008822:Mice, Transgenic / Q000235:genetics*; D010088:Oxidoreductases / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000235:genetics* / Q000378:metabolism
D015259:Dopamine Agents; D008054:Lipid Peroxides; D008694:Methamphetamine; D008315:Malondialdehyde; D010088:Oxidoreductases; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D005978:Glutathione