Effect of Smoking Cessation on Mitochondrial Respiratory Chain Function

Abstract

Objective. Chronic smoking has been associated with diverse mitochondrial respiratory chain (MRC) dysfunction in lymphocytes, although inhibition of complex IV activity is the most consistent and relevant finding. These mitochondrial abnormalities have been proposed to contribute to pathogenesis of diseases associated with tobacco consumption. We assessed MRC function in peripheral lymphocytes from heavy smokers after cessation in smoking habit. Patients and Methods. We studied MRC function from peripheral lymphocytes of 10 healthy chronic smoker individuals (age 43±6 years; 50% women) before cessation of tobacco consumption (t₀), and 7 (t₁) and 28 (t₂) days after cessation. Smoking abstinence was ascertained by measuring carboxyhemoglobin levels and carbon monoxide (CO) concentration in exhaled breath. Ten healthy nonsmoker individuals matched by age and gender were used as controls. Lymphocytes were isolated by Ficoll's gradient, and protein content was determined by Bradford's technique. MRC function was studied through double means: 1) individual enzyme activities of complex II, III, and IV were analyzed by means of spectrophotometry; 2) oxygen consumption was measured polarographically using pyruvate, succinate, and glycerol-3-phosphate (complex I, II, and III substrates, respectively) after lymphocyte permeabilization. Enzyme and oxidative activities were corrected by citrate synthase activity. Results. Smokers showed a significant decrease in complex IV activity (p=0.05) and also in respiration of intact lymphocytes (p=0.05) compared to controls. Eight chronic smokers remained abstinent during the study. Smoking cessation was associated with a significant recovery of complex IV (p=0.01) and complex III (p=0.05) activities. Oxidative activities did not show any change during the study. Conclusion. Chronic smoking is associated with a decrease of complex IV and III activities of MRC, which return to normal values after cessation of tobacco smoking.