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Plasma oxidative stress (OS) including total homocysteine (tHcy) and malondialdehyde (MDA) concentrations is usually elevated and antioxidant enzymes activities are decreased in patients suffering from chronic kidney disease. It is thought that OS in these patients may have a role in the pathophysiology of cardiovascular events. It has been suggested that N-acetylcysteine (NAC) may be effective to lower OS. This study was designed to evaluate the possible effect of 4-week treatment with oral NAC on plasma tHcy and MDA concentrations and status of antioxidant enzymes in chronic hemodialysis (HD) patients who were receiving vitamin B group at least from the onset of dialysis program. Twenty patients were enrolled in this study. All subjects were treated with oral NAC (600 mg twice daily) for 4 weeks. Predialysis plasma tHcy and MDA concentrations and activities of glutathione peroxidase, catalase, and superoxide dismutase were assessed before the initiation of NAC and after 4-week NAC therapy. At baseline, moderately severe hyperhomocysteinemia was present in about 63% of patients. The results showed significant (19%) decline in plasma tHcy concentration after NAC therapy. However, moderately severe hyperhomocysteinemia was persistently seen in about 50% of the patients. NAC did not affect concentration of MDA and antioxidant enzymes activities. Because of the proposed relationship between cardiovascular morbidity and hyperhomocysteinemia in patients on HD, daily supplementation of patients with NAC may be recommended as adjunct to vitamins in those subjects who did not respond adequately to group B vitamins alone.