Lipid peroxidation is increased in paraoxonase L55 homozygotes compared with M-allele carriers

Hum;in serum paraoxonase (PON) is an antioxidative enzyme, which circulates on high-density lipoproteins and appears to use oxidized phospholipids as physiological substrates. PON M/L55 substitution changes the ability of PON to prevent lipid oxidation. Urinary 8-iso-PGF(2 alpha) (one of F-2-isopros tanes) may represent a non-invasive in vivo index of free radical generatio n and we propose that PON might influence the biosynthesis of 8-iso-PGF(2 a lpha), in the vasculature. We studied the urinary excretion of 8-isn-PGF(2 alpha) and related it to PON M/L55 genotypes in patients with type 2 diabet es mellitus (n = 55) and non-diabetic control subjects (n = 55). Urinary 8- iso-PGF(2 alpha) was determined by competitive ELISA and the PON genotype b y a PCI;: based restriction enzyme digestion method. LL homozygotes were co mpared to M-allele carriers (ML hetero-zygotes and MM homozygotes). The uri nary excretion of 8-iso-PGF(2 alpha) among non-diabetic non-smoking LL homo zygotes tvas 3995.5 +/- 3352.5 ng/24-hour and among M-allele carriers 1689. 11 +/- 1051.3 ng/24-hour (p = 0.017, ANCOVA; gender, hypertension, total ch olesterol, triglycerides and LDL cholesterol as covariates). The excretion of 8-iso-PGF(2 alpha), was increased in type 2 diabetes mellitus compared t o non-diabetic control subjects. PON may thus protect against oxidative str ess by destroying some biologically active lipids. Excretion of 8-iso-PGF(2 alpha) is increased in type 2 diabetes, which ma!: reflect oxidant injury.