Smoking disturbs mitochondrial respiratory chain function and enhances lipid peroxidation on human circulating lymphocytes

Mitochondria constitute a source of reactive oxygen species. We tested whet her mitochondrial function from human circulating lymphocytes is affected b y smoking habit and if this could be associated with an increase in oxidati ve damage of biological membranes. We prospectively studied 35 smokers and 35 non-smoking healthy individuals matched by age and sex, with a similar p hysical activity. Individual enzyme activity of complexes LI, III and IV of the mitochondrial respiratory chain (MRC) and of glycerol-3-phosphate dehy drogenase activity were measured spectrophotometrically. Intact cell respir ation and oxidative rates after addition of pyruvate, succinate and glycero l-3-phosphate were assessed polarographically. Lipid peroxidation of biolog ical membranes was assessed measuring the loss of cis-parinaric acid fluore scence. Results are expressed as means(+/-SD). Smokers showed a significant decrease in complex IV activity compared with non-smokers (112.8 +/- 40.9 versus 146.4 +/- 62.5 nmol/min/mg protein, respectively; 23% of inhibition; P = 0.01), while the rest of the complexes of MRC were unaffected. Convers ely, oxidative rate with succinate, but not with the other substrates, was enhanced in smokers compared with non-smokers (16.7 +/- 10.4 versus 11.4 +/ - 4.7 nmol oxygen/min/mg protein, respectively; 46% of activation; P 0.01). Lipid peroxidation of lymphocyte membranes was increased in smokers with r espect to non-smokers (3.49 +/- 1.27 versus 4.39 +/- 1.76 units of fluoresc ence/mg protein, respectively; 21% of increase; P = 0.03) and this increase correlated positively with succinate oxidation activation (R = 0.34, P = 0 .02) and, to a lesser extent, with complex IV inhibition, although it did n ot reach statistical significance (R = 0.19, P = 0.18). In smokers, the MRC function of lymphocytes is disturbed and correlates with the degree of oxi dative damage of membranes, This mitochondrial dysfunction could contribute to increased endogenous production of reactive oxygen species and could pl ay a role in tobacco carcinogenicity.