Metallothionein inducers protect against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine neurotoxicity in mice.
1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is a drug that induces parkinsonism in human and non-human primates. Free radicals are thought to be involved in its mechanism of action. Recently, the participation of metallothionein as scavenger of free radicals has been proposed. In this work, we studied the effect of metallothionein inducers in MPTP neurotoxic action. Male swiss albino mice were pretreated either with cadmium (1 mg/kg) or dexamethasone (5 mg/kg), two well-known inducers of metallothionein synthesis, and 5 hours later with an MPTP administration (30 mg/kg). Treatment schedule was repeated daily for either 3 or 5 consecutive days. All animals were killed 7 days after the last administration, and striatal dopamine and homovanillic acid contents were analyzed as an end-point of MPTP neurotoxicity. Striatal dopamine content of cadmium plus MPTP-treated animals (3-days) increased by 32%, and 48% (5-days) vs MPTP-alone animals. Dexamethasone plus MPTP-treated group also showed increased dopamine levels 28% (3-days) and 43% (5-days). MPTP treatment reduced striatal metallothionein concentration (49% vs control animals). Dexamethasone and cadmium increased metallothionein concentrations in MPTP-treated groups, by 77% and 82% respectively. Results suggest that metallothionein induction provide a significant resistance factor against the deleterious effect of MPTP.
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Departamento de Neuroquímica, Instituto Nacional de Neurología y Neurocirugía, Manuel Velasco Suárez, México, D.F.
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D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000037:antagonists & inhibitors; D000818:Animals; D002104:Cadmium / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D015259:Dopamine Agents / Q000633:toxicity*; D004790:Enzyme Induction; D020267:MPTP Poisoning; D008297:Male; D008668:Metallothionein / Q000096:biosynthesis*; D051379:Mice; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009498:Neurotoxins / Q000037:antagonists & inhibitors / Q000633:toxicity*
D015259:Dopamine Agents; D018696:Neuroprotective Agents; D009498:Neurotoxins; D002104:Cadmium; D003907:Dexamethasone; D008668:Metallothionein; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine