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Protection of methamphetamine nigrostriatal toxicity by dietary selenium
1Department of Pharmacy, College of Pharmacy, Kangwon National University, Korea Institute of Drug Abuse, Chunchon, South Korea. kimhc@cc.kangwon.ac.kr
Abstract:
Multiple dose administration of methamphetamine (MA) results in long-lasting toxic effects in the nigrostriatal dopaminergic system. These effects are considered to be primarily due to oxidative damage mediated by increased production of hydrogen peroxide or other reactive oxygen species in the dopaminergic system. The present study was designed to determine the protective effects of dietary antioxidant selenium on MA-induced neurotoxicity in the nigrostriatal dopaminergic system. Male C57BL/6J mice were fed either selenium-deficient (< 0.01 ppm Se) or selenium-replete (0.2 ppm Se) diets for 90 days. MA treatment decreased the dopamine (DA) levels in the striatum and substantia nigra (SN) of both Se-replete and Se-deficient animals. However, in Se-replete animals, this DA depletion was significantly attenuated in both the striatum and SN. A novel observation is that MA administration resulted in increased activity of Cu,Zn-SOD in the brains of both Se-deficient and Se-replete animals. However, MA administration to Se-deficient animals exhibited a higher Cu,Zn-SOD activity in the nigrostriatal system than the control animals. Elevated malondialdehyde (MDA) levels in the striatum and SN were also observed in Se-deficient MA-treated animals. Se repletion significantly increased the glutathione peroxidase (GPx) activity and the ratio of reduced glutathione (GSH)/oxidized glutathione (GSSG) in the MA-treated animals. In conclusion, we have shown that dietary Se attenuated methamphetamine neurotoxicity and that this protection involves GPx-mediated antioxidant mechanisms. Even though Cu,Zn-SOD activity was significantly elevated by MA treatment, the role of this enzyme in MA-mediated neurotoxicity is not yet clear.
Insights
Dietary selenium (Se) protects against methamphetamine (MA) neurotoxicity by enhancing antioxidant mechanisms like glutathione peroxidase (GPx). This study shows Se repletion attenuates MA-induced dopamine depletion in mice.
Area of Science:
- Neuroscience
- Toxicology
- Nutritional Biochemistry
Background:
- Methamphetamine (MA) causes long-lasting damage to the nigrostriatal dopaminergic system.
- This neurotoxicity is primarily linked to oxidative stress and reactive oxygen species.
- Dietary antioxidants may offer protection against such neurotoxic effects.
Purpose of the Study:
- To investigate the protective effects of dietary selenium (Se) against methamphetamine-induced neurotoxicity.
- To examine the role of selenium in modulating oxidative stress markers in the dopaminergic system.
Main Methods:
- Male C57BL/6J mice were fed selenium-deficient or selenium-replete diets for 90 days.
- Methamphetamine was administered to assess neurotoxicity.
- Dopamine levels, Cu,Zn-superoxide dismutase (SOD) activity, malondialdehyde (MDA) levels, and glutathione peroxidase (GPx) activity were measured.
Main Results:
- Methamphetamine administration decreased dopamine levels in both selenium-replete and deficient mice.
- Selenium repletion significantly attenuated this dopamine depletion in the striatum and substantia nigra.
- Selenium repletion increased glutathione peroxidase activity and the reduced glutathione/oxidized glutathione ratio in methamphetamine-treated mice.
Conclusions:
- Dietary selenium significantly attenuates methamphetamine-induced neurotoxicity in the nigrostriatal dopaminergic system.
- The protective mechanism involves enhanced glutathione peroxidase-mediated antioxidant activity.
- The role of elevated Cu,Zn-SOD activity in methamphetamine neurotoxicity requires further investigation.