Etsuo Niki, Free Radical Biology & Medicine, Health Technology Research Center, National Institute of Advanced Industrial Science & Technology, Ikeda, Osaka 563-8577, Japan

Lipid peroxidation (LPO) has been shown to induce disturbance of membrane organization and functional loss and modification of proteins and DNA bases, and it has been implicated in the pathogenesis of various diseases. At the same time, LPO products have been shown to act as redox signaling mediators. Free and ester are oxidized by both enzymatic and nonenzymatic mechanisms to give a variety of products. The results of numerous studies reported in the literatures show that the levels of LPO products in plasma of healthy human subjects are below 1 μM and that the molar ratios of LPO products to the respective parent lipids are below 1/1000, that is, below 0.1%. The levels of LPO products in human erythrocytes were found to be higher 28 than those in plasma. Considerable levels of cholesterol oxidation products were observed. Although many 29 LPO products exert cyctotoxicity, sublethal concentrations of LPO products induce cellular adaptive responses and enhance tolerance against subsequent oxidative stress through upregulation of antioxidant compounds and enzymes. This adaptive response is observed not only for chemically reactive α,β-unsaturated carbonyl compounds such as 4-hydroxy-2-nonenal and 15-deoxy-delta-12,14-prostaglandin J2 but also for chemically stable compounds such as hydroxyoctadecadienoic acid, hydroxylcholesterol, and lysophosphatidylcholine. Such opposite dual functions of LPO products imply that LPO, and probably oxidative stress in general, may exert both deleterious and beneficial effects in vivo. LPO as well as reactive oxygen and nitrogen species has been shown to play an important role as a regulator of gene expression and cellular signaling messenger. In order to exert physiologically important functions as a regulator of gene expression and mediator of cellular signaling, the formation of LPO products must be strictly controlled and programmed. In contrast to LPO products by enzymatic oxidation, it appears difficult to regulate the formation of free radical-mediated LPO products. Even such unregulated LPO products may exert beneficial effects at low levels, but excessive unregulated LPO may lead to pathological disorders and diseases.

Joachim Bleys, Ana Navas-Acien, Martin Laclaustra, Roberto Pastor-Barriuso, Andy Menke,
Jose Ordovas, Saverio Stranges, and Eliseo Guallar

The authors conducted a cross-sectional study of the association of serum selenium with the prevalence of peripheral arterial disease among 2,062 US men and women 40 years of age or older participating in the National Health and Nutrition Examination Survey, 2003–2004. Serum selenium was measured by using inductively coupled plasma-dynamic reaction cell-mass spectrometry. Peripheral arterial disease was defined as an anklebrachial blood pressure index less than 0.90. The age-, sex-, and race-adjusted prevalence of peripheral arterial disease decreased with increasing serum selenium (P for linear trend 1/4 0.02), but there was an indication of an upturn in risk in the highest quartile of serum selenium. The fully adjusted odds ratios for peripheral arterial disease comparing selenium quartiles 2, 3, and 4 with the lowest quartile were 0.75 (95% confidence interval: 0.37, 1.52), 0.58 (95% confidence interval: 0.28, 1.19), and 0.67 (95% confidence interval: 0.34, 1.31), respectively. In spline regression models, peripheral arterial disease prevalence decreased with increasing serum selenium levels up to 150–160 ng/mL, followed by a gradual increase at higher selenium levels. The association between serum selenium levels and the prevalence of peripheral arterial disease was not statistically significant, although a U-shaped relation was suggested.