Effects of pergolide mesilate on metallothionein mRNAs expression in a mouse model for Parkinson disease.
Dopamine agonists have neuroprotective properties in addition to their original pharmacologic function. We examined the effects of pergolide mesilate (PM) on the levels of metallothionein mRNA expression and lipid peroxidation in the corpus striata of 1-methyl 4-phenyl 1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinsonian mice. Mice were administered normal saline (vehicle as a control), PM, or MPTP. A consecutive 7-d administration of MPTP via a gastric tube at a dose of 30 mg/kg significantly decreased metallothionein (MT)-I mRNA expression but did not influence MT-III mRNA expression. Lipid peroxidation, measured as the production of malondialdehyde reactive substances, did not increase after MPTP treatment. Although PM administration alone did not effect MT-I expression, an additional consecutive 7-d administration of PM (30 mug/kg) following MPTP treatment recovered the decreased MT-I level and increased MT-III expression. Lipid peroxidation was significantly suppressed. These results suggest that PM exerts an antioxidative property through the induction of MT-I and MT-III mRNAs simultaneously in response to cellular and/or tissue injury.
Research Unit of Clinical Pharmacy, College of Pharmacy, Nihon University, Funabashi, Chiba274-8555, Japan. ono.shinichi@nihon-u.ac.jp
Shin-ichi
S
Ono
Kohji
K
Hirai
Ei-ichi
E
Tokuda
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D001921:Brain / Q000187:drug effects*; D004195:Disease Models, Animal; D018491:Dopamine Agonists / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D015870:Gene Expression / Q000187:drug effects; D015227:Lipid Peroxidation / Q000187:drug effects*; D008315:Malondialdehyde / Q000378:metabolism; D008668:Metallothionein / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D010300:Parkinson Disease / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D010479:Pergolide / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000378:metabolism
D000975:Antioxidants; D018491:Dopamine Agonists; D012333:RNA, Messenger; D010479:Pergolide; D008315:Malondialdehyde; D008668:Metallothionein; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine