Metallothionein-I and -II knock-out mice are not more sensitive than control mice to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine neurotoxicity.
Oxidative stress, resulting from either excess generation or reduced scavenging of free radicals, has been proposed to play a role in damaging striatal neurons in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) neurotoxicity. Metallothionein (MT) is a scavenger of oxygen-derived free radicals and it has been suggested that MT protects against oxidative damage in the central nervous system. In the present study we compared MT-I and -II null mice (MT-null) and the parental strain with intact metallothionein genes (control mice) to determine whether the absence of MT protein alters MPTP neurotoxicity. Control and MT-null mice were treated with MPTP at different doses (30, 40 and 50 mg/kg, i.p.) for 11 days. Seven days after the last dose, brains were removed and dopamine (DA) and homovanillic acid (HVA) contents were analyzed in striatum and midbrain by high pressure liquid chromatography (HPLC). Striatal DA content in MPTP-treated control mice was reduced by 53, 74 and 84% after 30, 40 and 50 mg/kg, respectively. Similar decreases were observed in MT-null mice treated with MPTP. MT-null mice were not more sensitive than control mice to MPTP neurotoxicity. The data suggest that MT-I and -II proteins do not play a role in protecting against MPTP neurotoxicity.
Rojas
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Center for Environmental and Occupational Health, Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City 66160-7417, USA.
Klaassen
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D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000494:pharmacology*; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D003342:Corpus Striatum / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D018492:Dopamine Antagonists / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance; D006719:Homovanillic Acid / Q000378:metabolism; D008636:Mesencephalon / Q000378:metabolism; D008668:Metallothionein / Q000172:deficiency* / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout / Q000235:genetics; D009498:Neurotoxins / Q000494:pharmacology*; D012016:Reference Values
D018492:Dopamine Antagonists; D009498:Neurotoxins; D008668:Metallothionein; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D004298:Dopamine; D006719:Homovanillic Acid