Increase of formation of methylamine and formaldehyde in vivo after administration of nicotine and the potential cytotoxicity.
Methylamine is a constituent of cigarette smoke and the major end product of nicotine metabolism. Smoking or nicotine can induce the release of adrenaline, which is in turn deaminated by monoamine oxidase, also producing methylamine. We found that the urinary level of methylamine was significantly elevated following administration of nicotine (25 mg/Kg, i.p.). Semicarbazide-sensitive amine oxidase (SSAO) inhibitors further increased the excretion of methylamine induced by nicotine. Following administration of L-(-)-[N-methyl-3H]nicotine long-lasting irreversible radioactive adducts were detected in different mouse tissues and such adduct formation could be blocked by selective SSAO inhibitors. These adducts are probably cross-linked oligoprotein complexes cross-linked by formaldehyde. The findings support the idea that nicotine can enhance SSAO/methylamine-mediated increase of formaldehyde and oxidative stress and this could in part contribute the adverse effect of health associated with smoking.
Department of Psychiatry, University of Saskatchewan, Saskatoon, Canada. YUP@SASK.USASK.CA
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D000498:Allyl Compounds / Q000494:pharmacology; D006631:Amine Oxidase (Copper-Containing) / Q000037:antagonists & inhibitors; D000818:Animals; D001711:Biotransformation; D002082:Butylamines / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005557:Formaldehyde / Q000493:pharmacokinetics* / Q000633:toxicity; D008297:Male; D008744:Methylamines / Q000493:pharmacokinetics* / Q000633:toxicity / Q000652:urine; D051379:Mice; D009538:Nicotine / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar; D012907:Smoking; D014018:Tissue Distribution; D014316:Tritium
D000498:Allyl Compounds; D002082:Butylamines; D004791:Enzyme Inhibitors; D008744:Methylamines; D014316:Tritium; C058000:mofegiline; D005557:Formaldehyde; D009538:Nicotine; C027451:methylamine; D006631:Amine Oxidase (Copper-Containing)