1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced neurotoxicity: partial protection against striato-nigral dopamine depletion in C57BL/6J mice by cigarette smoke exposure and by beta-naphthoflavone-pretreatment.
This study aimed to find a possible biochemical basis for the frequent epidemiological observation of a negative correlation between smoking and Parkinson's disease. The effects of cigarette smoke exposure and of beta-naphthoflavone (BNF)-pretreatment on corpus striatal dopamine depletion by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) were studied using the mouse MPTP model. Brain and hepatic monoamine oxidase (MAO) activity, hepatic cytochrome P450 content, BNF-inducible ethoxyresorufin O-dealkylase (EROD) activity and corpus striatal dopamine levels were measured. Cigarette smoke exposure partially protected against corpus striatial dopamine depletion by MPTP. This protection was associated with monomaine oxidase (MAO) inhibition in brain and liver, as well as with cytochrome P450 induction. BNF pretreatment also partially protected against MPTP-induced depletion of striatal dopamine. This was associated with a strong induction of cytochrome P450 but not inhibition of MAO activity. Our findings suggest that both MAO inhibition and cytochrome P450 induction may play a role in any biochemical protection afforded by cigarette smoke exposure against the development of Parkinson's disease.
Shahi
G S
GS
Department of Physiology, National University of Singapore.
Das
N P
NP
Moochhala
S M
SM
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000494:pharmacology*; D000818:Animals; D001571:Benzoflavones / Q000494:pharmacology*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D019363:Cytochrome P-450 CYP1A1; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008995:Monoamine Oxidase / Q000378:metabolism; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology; D009420:Nervous System / Q000187:drug effects / Q000378:metabolism; D010088:Oxidoreductases / Q000378:metabolism; D010300:Parkinson Disease / Q000378:metabolism; D010947:Plants, Toxic; D012906:Smoke / Q000009:adverse effects*; D014026:Nicotiana; D019324:beta-Naphthoflavone
D001571:Benzoflavones; D008996:Monoamine Oxidase Inhibitors; D012906:Smoke; D019324:beta-Naphthoflavone; D003577:Cytochrome P-450 Enzyme System; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D010088:Oxidoreductases; D019363:Cytochrome P-450 CYP1A1; D008995:Monoamine Oxidase; D004298:Dopamine