This single copy is for your personal, non-commercial use only. For permission to reprint multiple copies or to order presentation-ready copies for distribution, contact Multimed Inc. at marketing@multi-med.com Peritoneal Dialysis International, Vol. 30, pp. 336–342 doi: 10.3747/pdi.2009.00073 0896-8608/10 $3.00 + .00 Copyright © 2010 International Society for Peritoneal Dialysis 336 EFFECT OF ORAL N-ACETYLCYSTEINE TREATMENT ON PLASMA INFLAMMATORY AND OXIDATIVE STRESS MARKERS IN PERITONEAL DIALYSIS PATIENTS: A PLACEBO-CONTROLLED STUDY Marcelo M. Nascimento, 1,2 Mohamed E. Suliman, 2,3 Margarete Silva, 1 Tiago Chinaglia, 1 Josiane Marchioro, 1 Shirley Y. Hayashi, 2 Miguel C. Riella, 1 Bengt Lindholm, 2 and Björn Anderstam 2 Faculdade Evangélica de Medicina do Paraná-Brasil, 1 Curitiba, Brazil; Divisions of Renal Medicine and Baxter Novum, 2 Department of Clinical Science, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden; King Fahad Medical City, 3 Riyadh, Saudi Arabia Correspondence to: M. Mazza do Nascimento, Faculdade Evangélica de Medicina do Paraná-Brasil, Saldanha Marinho 1453, 3rd Floor, 80430-160, Curitiba, Paraná, Brazil. marcelo.mazza.do.nascimento@ki.se Received 2 April 2009; accepted 24 August 2009. ♦ Background: Inflammation and oxidative stress (OS) are cardiovascular risk factors in patients with chronic kidney disease. N-acetylcysteine (NAC) is a thiol-containing anti- oxidant with anti-inflammatory properties and has been shown to reduce the number of cardiovascular events in hemodialysis patients. ♦ Methods: The current study aimed to determine the ef- fect of oral NAC (2 × 600 mg/daily) on plasma levels of in- flammatory and OS markers in peritoneal dialysis (PD) patients. We performed a placebo-controlled study over 8 weeks in 30 patients (40% males, age 52 ± 13 years) on regular PD. Before the study was started, the patients were divided into 2 groups of 15 patients matched for age and gender. 22 patients completed the study (12 on NAC, 10 on placebo). Proinflammatory cytokines [high-sensitivity C-reactive protein, interleukin-6 (IL-6), tumor necrosis fac- tor-alpha, and pentraxin 3] and markers of OS (pentosidine, advanced oxidation protein products, homocysteine, glu- tathione, asymmetric dimethylarginine, and free sulfhydr- yls) were measured before and after treatment with NAC. ♦ Results: Treatment with NAC for 8 weeks increased mean baseline plasma NAC levels from 2.6 to 24.8 μmol/L (p = 0.007). This intervention, which caused no side effects, sig- nificantly diminished IL-6 levels, from 9.4 (4.5 – 31) to 7.6 (4.9 – 13.5) pg/mL (p = 0.006), whereas no such changes were observed in the placebo group. NAC treatment did not significantly affect the other inflammatory and OS markers. ♦ Conclusion: Short-term oral NAC treatment resulted in reduction of circulating IL-6, suggesting that such treat- ment could be a useful strategy in blunting the inflamma- tory response in PD patients. Perit Dial Int 2010; 30:336–342 www.PDIConnect.com epub ahead of print: 26 Feb 2010 doi: 10.3747/pdi.2009.00073 KEY WORDS: N-Acetylcysteine; oxidative stress; in- flammation; chronic kidney disease. T he presence of increased oxidative stress (OS) and per- sistent inflammation has been well documented in dialysis patients (1). Reactive oxygen species have del- eterious effects on different cells and may contribute to atherogenesis (2). Different antioxidant strategies have been evaluated with respect to reducing OS in patients with chronic kidney disease. Considering its safety, low cost, and possible benefits, N-acetylcysteine (NAC) might be a potential anti-inflammatory and antioxidant drug in dialysis patients. N-Acetylcysteine is a thiol-containing compound with antioxidant effects that can be attributed to its action as a free radical scavenger and as a reactive sulfhydryl compound that increases the reducing capacity of the cell (3). NAC has been used for many years for the treat- ment of chronic bronchitis, as a mucolytic drug, and as an antidote in paracetamol overdose (4). This compound has been found to be well tolerated without any serious side effects. Moreover, it has been demonstrated in vitro that NAC has a favorable influence on various T cell func- tions (2). In the nephrology area, NAC has been used for the prevention of contrast medium-induced nephropathy. In hemodialysis (HD) patients, it may lead to a significant reduction in cardiovascular events (5). In peritoneal di- alysis (PD), a couple of experimental (6) and in vitro (7) studies have demonstrated that NAC antioxidant prop- erties could be applied for preserving peritoneal mem- brane in rats and possibly decreasing intraperitoneal production of advanced glycation end products. How- ever, few data are available on its antioxidant and anti- inflammatory effects in PD patients. In the present study, we investigated the effect of NAC (2 × 600 mg/day) treat-