Effects of peroxidized polyunsaturated fatty acids on mitochondrial function and structure: pathogenetic implications...

Linoleic acid, a polyunsaturated fatty acid, is a constituent of margosa oil which has been implicated as a cause of Reye's syndrome (RS) in infants. Increased concentrations of polyunsaturated fatty acids have been found in sera from patients with RS. Isolated rat liver mitochondria exposed to the peroxidized (but not unperoxidized) methyl esters of linoleic (C18:2) or linolenic (C18:3) acids showed decreases in state 3 and uncoupled respiratory rates and in respiratory control and ADP/O ratios. In addition, they caused mitochondrial swelling as demonstrated spectrophotometrically. Between the two, the peroxidized methyl ester of linolenic acid was more toxic and was capable of inducing high amplitude swelling ultrastructurally similar to that seen in the hepatocytes of RS victims. The ability of rat liver mitochondria to oxidize glutamate was inversely related to the peroxide concentration in the medium. This accords with the reports of reduced glutamic dehydrogenase activities in the livers of both patients with Reye's syndrome and rats treated with margosa oil.