Simultaneous determination of formaldehyde and methylglyoxal in urine: involvement of semicarbazide-sensitive amine oxidase-mediated deamination in diabetic complications.
The deamination of methylamine and aminoacetone by semicarbazide-sensitive amine oxidase (SSAO) produces formaldehyde and methylglyoxal, respectively, which have been presumed to be involved in diabetic complications. A high-performance liquid chromatography procedure using 2,4-dinitrophenylhydrazine (DNPH) as a derivatizing agent is developed to determine endogenous formaldehyde, methylglyoxal, malondialdehyde, and acetaldehyde. The devised DNPH method is sensitive enough to analyze aldehyde levels in urine. An increase in the excretion of formaldehyde, methylglyoxal, and malondialdehyde is confirmed in streptozotocin-induced diabetic rats. Following the chronic administration of methylamine, the urinary levels of both formaldehyde and malondialdehyde (a product from lipid peroxidation) are found to be substantially increased. A potent selective SSAO inhibitor, (E)-2-(4-fluorophenethyl)-3-fluoroallylamine hydrochloride (MDL-72974A), reduced the formation of formaldehyde, methylglyoxal, and malondialdehyde. The increase of the cytotoxic aldehyde levels as a result of increased SSAO-mediated deamination may occur in some pathological conditions.
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Department of Psychiatry, University of Saskatchewan, Saskatoon, Canada.
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D006631:Amine Oxidase (Copper-Containing) / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D003921:Diabetes Mellitus, Experimental / Q000150:complications* / Q000652:urine; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005557:Formaldehyde / Q000652:urine*; D008297:Male; D008315:Malondialdehyde / Q000652:urine; D008744:Methylamines / Q000008:administration & dosage / Q000378:metabolism; D010659:Phenylhydrazines; D011765:Pyruvaldehyde / Q000652:urine*; D051381:Rats; D017208:Rats, Wistar; D012663:Semicarbazides / Q000494:pharmacology*; D012680:Sensitivity and Specificity
D004791:Enzyme Inhibitors; D008744:Methylamines; D010659:Phenylhydrazines; D012663:Semicarbazides; D005557:Formaldehyde; C004787:2,4-dinitrophenylhydrazine; C010059:carbamylhydrazine; D008315:Malondialdehyde; D011765:Pyruvaldehyde; C027451:methylamine; D006631:Amine Oxidase (Copper-Containing)