The pharmacodynamic effect of N-acetylcysteine as adjunctive therapy in mild Systemic Lupus Erythematosus (SLE) patients

Abstract

N-acetylcysteine (NAC), a strong free radical scavenger, was designed to use as adjunctive therapy in mild systemic lupus erythematosus (SLE) to correct an imbalance of antioxidant status which is previously reported in SLE patients. This study was divided into 3 parts. Firstly, epidemiology and drug pattern used which were determined by the prevalence of SLE in department of medicine, Ramathibodi hospital, Thailand during 2000-2006 while the drug pattern information was recorded and was compared to standard guideline therapy. Secondly, the oxidative status was compared among 54 SLE patients with different degree of severity of the disease (mid =20, severe=14) and among 20 healthy volunteers; plasma glutathione (GSH; a natural antioxidant) and plasma malondialdehyde (MDA; the marker of lipid peroxidation) were measured. Thirdly, pharmacodynamic effect of NAC in term of alteration in plasma GSH and plasma MDA levels as compare to that in the control group and in mild SLE patients (n=20 in each group) for 6 months. The results indicated that the prevalence of SLE was ranged from 267-552 per 100,000 visitors. Prednisolone containing regimens and combined-drug were frequently prescribed in SLE patients. The four main drugs; prednisolone, chloroquine, azathioprine, and hydroxychloroquine were used. The significant association between SLE duration and the proportion (percentage) of patients who received azathioprine was found. In part of oxidative stress monitoring, there was a significant correlation of plasma GSH level and SLE severity (measured by systemic lupus erythematosus disease activity index, SLEDAI score), p<0.05. Whereas, such correlation was not observed in termed of plasma MDA. Finally, NAC administration was beneficial in significant reducing plasma MDA level at 6 months (0.507±0.274 vs 0.354±0.178 µM, p=0.023), while plasma GSH was not shown to be significant difference. Furthermore, significant higher proportion of SLE patients who could taper prednisolone dosage was found in NAC group (p<0.05). It can be concluded that NAC seems to be beneficial in reducing plasma MDA level and associate in tapering prednisolone in mild SLE patients. The pharmacodynamic effects of NAC should be expand to investigated in more severe SLE patients to make a more confident conclusion on the benefit of using NAC as an adjunctive therapy in SLE patients.