Smoking Is Associated with Alterations of Blood Thiol-Group Related Antioxidants in Patients on Hemodialysis

Abstract

Cardiovascular disease is the major complication and cause of mortality in the dialysis population, accounting for about 40% of deaths. Oxidative stress has been strongly implicated in the pathogenesis of these events. As patients in end-stage renal disease (ESRD) are in a state of elevated free radical activity, the aim of the present study was to investigate the negative impact of smoking in 45 male hemodialysis (HD) patients. These patients, who were 40–85 years of age (mean age 60.9 ± 13.3 years), had been on hemodialysis for at least 12 months before participating in this study. Fasting blood sampling for serum lipid, albumin, urate, lipid peroxides total blood glutathione (tGSH), non-GSH free sulfhydryl compounds (non-GSH fSH), plasma glutathione peroxidase (pGSHPx), erythrocytes glutathione peroxidase (rGSHPx), plasma glutathione S-transferase (pGST) and erythrocytes glutathione S-transferase (rGST) were determined. Our study showed that the plasma malonyldialdehyde (MDA) concentration was significantly higher in HD patients who smoked than in those who were non- smokers (1.99 ± 0.53 vs. 1.55 ± 0.46 nmol/ml, p = 0.008). No association was found between levels of MDA in smokers and BMI, serum cholesterol and triglycerides and smoking index. We also found that the circulating plasma levels of tGSH and non-GSH fSH was lower in the HD patients who smoked (tGSH 164.9 ± 41.5 vs. 203.4 ± 45.3 µg/ml; fSH 271.1 ± 55.8 vs. 308.8 ± 46.7 µg/ml; p < 0.05 and p < 0.001, respectively). There were no significant differences in the plasma levels of uric acid, pGSHPx, rGSHPx, pGST, rGST, albumin, and age between the 2 groups. Partial correlation analysis of the plasma levels of the measured antioxidants and the smoking index revealed a negative correlation between the plasma levels of tGSH and smoking index (r = –0.62, p < 0.003). Similarly, the plasma levels of tGSH was found negatively correlated with the levels of plasma MDA (r = –0.32, p < 0.05) of the HD patients. In conclusion, our data suggest that cigarette smoking has a negative impact on plasma-circulating products of lipid peroxidation in HD patients. The lower blood levels of the tGSH and non-GSH fSH in HD patients who smoked suggests that these patients may be more susceptible to oxidative damage caused by smoking.

Effects of Zinc Supplementation on Antioxidant Status and Lipid Peroxidation in Hemodialysis Patients

“…Our findings are in agreement with the results of previous studies reporting higher levels of MDA and lower levels of GSH in the patients on HD or with chronic renal failure. [22][23][24][25][26] Moreover, Ozden et al 11 have reported that the serum levels of MDA increased in HD patients when the erythrocyte glutathione level decreased.…”

“…34 In the study presented here, BMI values were in the normal range and did not change after the study periods whereas there was a significant difference in BMI between case and control groups in some of previous studies. 22,35 Furthermore, the crossover design of the study presented here helped to control possible confounding factors. However, the possible limitation of our study is that the erythrocyte zinc level was not assessed.…”

Endothelial Function and Aminothiol Biomarkers of Oxidative Stress in Healthy Adults

“…This suggests that it may be a more accurate reflection of intracellular rather than extracellular oxidant/ antioxidant balance. Clinical studies have demonstrated increased oxidative stress with reduced circulating GSH and increased GSSG levels with aging beyond the age 45 years, 20,23,27 type 2 diabetes, 23 high dose chemotherapy, 28 cigarette smoking, 29 and increased carotid thickening. 30 …”

Cysteine/cystine redox signaling in cardiovascular disease

“…Patients and healthy subjects who smoked showed decreased GSH levels in platelet, bronchial tissues, serum and plasma compared with non-smokers [30, 54, 55]. A study of hemodialysis (HD) patients who smoked showed that the circulating plasma levels of GSH and non-GSH plasma thiols, including Cys, were substantially lower than those in non-smoking HD patients [56]. Chronic smokers had impaired platelet-derived nitric oxide (PDNO) production and augmented platelet aggregation.…”