Effect of alpha-tocopherol and deferoxamine on methamphetamine-induced neurotoxicity.
Methamphetamine (MA)-induced dopaminergic neurotoxicity is believed to be associated with the increased formation of free radicals. This study examined the effect of alpha-tocopherol (alpha-TC), a scavenger of reactive oxygen species, and deferoxamine (DFO), an iron chelator, on the MA-induced neurotoxicity. Male rats were treated with MA (10 mg/kg, every 2 h for four injections). The rat received either alpha-TC (20 mg/kg) intraperitoneally for 3 days and 30 min prior to MA administration or DFO (50 mg/kg) subcutaneously 30 min before MA administration. The concentrations of dopamine (DA), serotonin and their metabolites decreased significantly after MA administration, which was inhibited by the alpha-TC and DFO pretreatment. alpha-TC and DFO attenuated the MA-induced hyperthermia as well as the alterations in the locomotor activity. The level of lipid peroxidation was higher and the reduced glutathione concentration was lower in the MA-treated rats. These changes were significantly attenuated by alpha-TC and DFO. This suggests that alpha-TC and DFO ameliorate the MA-induced neuronal damage by decreasing the level of oxidative stress.
Park
Mee-Jung
MJ
Dept. of Forensic science, National Institute of Scientific Investigation, Yangchon-ku, Seoul, 158-707, Korea.
Lee
Sang-Ki
SK
Lim
Mi-Ae
MA
Chung
Hee-Sun
HS
Cho
Sung-Ig
SI
Jang
Choon-Gon
CG
Lee
Sun-Mee
SM
D000704:Analysis of Variance; D000818:Animals; D015306:Biogenic Monoamines / Q000378:metabolism; D001831:Body Temperature / Q000187:drug effects; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D003676:Deferoxamine / Q000008:administration & dosage*; D004334:Drug Administration Schedule; D004347:Drug Interactions; D005978:Glutathione / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008694:Methamphetamine; D009043:Motor Activity / Q000187:drug effects; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D020258:Neurotoxicity Syndromes / Q000209:etiology* / Q000517:prevention & control*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D024502:alpha-Tocopherol / Q000008:administration & dosage*
D015306:Biogenic Monoamines; D018696:Neuroprotective Agents; D008694:Methamphetamine; D005978:Glutathione; D024502:alpha-Tocopherol; D003676:Deferoxamine