Identification of 4-hydroxynonenal as a cytotoxic product originating from the peroxidation of liver microsomal lipids.
During the NADPH-Fe induced peroxidation of liver microsomal lipids, products are formed which show various cytopathological effects including inhibition of microsomal glucose-6-phosphatase. The major cytotoxic substance has been isolated and identified as 4-hydroxy-2,3-trans-nonenal. The structure was ascertained by means of ultraviolet, infrared and mass spectrometry and high-pressure liquid chromatographic analysis. Moreover, 4-hydroxynonenal, prepared by chemical synthesis, was found to reproduce the biological effects brought about by the biogenic aldehyde. Preliminary investigations suggest that as compared to 4-hydroxynonenal very low amounts of other 4-hydroxyalkenals, namely 4-hydroxyoctenal, 4-hydroxydecenal and 4-hydroxyundecenal are also formed by actively peroxidizing liver microsomes. In the absence of NADPH-Fe liver microsomes produced only minute amounts of 4-hydroxyalkenals. The biochemical and biological effects of synthetic 4-hydroxyalkenals have been studied in great detail in the past. The results of these investigations together with the finding that 4-hydroxyalkenals, in particular 4-hydroxynonenal, are formed during NADPH-Fe stimulated peroxidation of liver microsomal lipids, may help to elucidate the mechanism by which lipid peroxidation causes deleterious effects on cells and cell constituents.
D000447:Aldehydes / Q000032:analysis* / Q000494:pharmacology; D000818:Animals; D005952:Glucose-6-Phosphatase / Q000037:antagonists & inhibitors; D007700:Kinetics; D008054:Lipid Peroxides / Q000378:metabolism*; D008297:Male; D013058:Mass Spectrometry; D008862:Microsomes, Liver / Q000378:metabolism*; D009249:NADP; D010659:Phenylhydrazines; D051381:Rats; D013053:Spectrophotometry; D013329:Structure-Activity Relationship
D000447:Aldehydes; D008054:Lipid Peroxides; D010659:Phenylhydrazines; C004787:2,4-dinitrophenylhydrazine; D009249:NADP; D005952:Glucose-6-Phosphatase; C027576:4-hydroxy-2-nonenal