Formaldehyde produced endogenously via deamination of methylamine. A potential risk factor for initiation of endothelial injury.
Methylamine can be converted by semicarbazide-sensitive amine oxidase (SSAO) to formaldehyde and hydrogen peroxide, which have been proven to be toxic towards cultured endothelial cells. We investigated whether or not these deaminated products from methylamine can exert potentially hazardous toxic effects in vivo. Long lasting residual radioactivity in different tissues was detected following administration of [14C]-methylamine in the mouse. Approximately 10% of the total administered radioactivity could even be detected 5 days after injection of [14C]-methylamine. Eighty percent of the formation of irreversible adducts can be blocked by a highly selective SSAO inhibitor, (E)-2-(4-fluorophenethyl)-3-fluoroallylamine hydrochloride (MDL-72974A). The residual radioactivity was primarily associated with the insoluble tissue components and the soluble macromolecules. Radioactively labelled macromolecules were fragmented following enzymatic proteolysis. Results suggest that the formaldehyde derived from methylamine interacts with proteins in vivo. In the streptozotocin-induced diabetic mice, both SSAO activity and the formation of residual radioactivity were found to be significantly increased in the kidney. Chronic administration of methylamine enhances blood prorenin level, which strongly suggests that uncontrolled deamination of methylamine may be a risk factor for initiation of endothelial injury, and subsequent genesis of atherosclerosis.
Yu
P H
PH
Department of Psychiatry, University of Saskatchewan, Saskatoon, Canada.
Zuo
D M
DM
D000498:Allyl Compounds / Q000494:pharmacology; D006631:Amine Oxidase (Copper-Containing) / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000818:Animals; D002082:Butylamines / Q000494:pharmacology; D003641:Deamination; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism; D004730:Endothelium, Vascular / Q000293:injuries* / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004792:Enzyme Precursors / Q000097:blood; D005557:Formaldehyde / Q000378:metabolism*; D006861:Hydrogen Peroxide / Q000378:metabolism; D007668:Kidney / Q000378:metabolism; D008297:Male; D008744:Methylamines / Q000493:pharmacokinetics*; D051379:Mice; D012083:Renin / Q000097:blood; D012307:Risk Factors; D013311:Streptozocin
D000498:Allyl Compounds; D002082:Butylamines; D004791:Enzyme Inhibitors; D004792:Enzyme Precursors; D008744:Methylamines; C058000:mofegiline; D005557:Formaldehyde; D013311:Streptozocin; D006861:Hydrogen Peroxide; C027451:methylamine; D006631:Amine Oxidase (Copper-Containing); D012083:Renin