N-Acetylcysteine Reduces Disease Activity by Blocking Mammalian Target of Rapamycin in T Cells From Systemic Lupus Erythematosus Patients

تاریخ : ۱۳۹۳/۰۲/۲۸ / تعداد بازدید : ۲۳۵

Objective
Systemic lupus erythematosus (SLE) patients exhibit T cell dysfunction, which can be regulated through mitochondrial transmembrane potential (__m) and mammalian target of rapamycin (mTOR) by glutathione (GSH). This randomizeddouble-blind, placebo-controlled study was undertaken to examine the safety, tolerance, and efficacy of the GSH precursor N-acetylcysteine (NAC)

 

Methods

A total of 36 SLE patients received either daily placebo or 1.2 gm, 2.4 gm, or 4.8 gm of NAC. Disease activity was evaluated monthly by the British Isles Lupus Assessment Group (BILAG) index, the SLE Disease Activity Index (SLEDAI), and the Fatigue Assessment Scale (FAS) before, during, and after a 3-month treatment period. Mitochondrial transmembrane potential and mTOR were assessed by flow cytometry . Forty-two healthy subjects matched to patients for age, sex, and ethnicity were studied as controls

 

Results

NAC up to 2.4 gm/day was tolerated by all patients, while 33% of those receiving 4.8 gm/day had reversible nausea. Placebo or NAC 1.2 gm/day did not influence disease activity. Considered together, 2.4 gm and 4.8 gm NAC reduced the SLEDAI score after1 month (P _ 0.0007), 2 months (P _ 0.0009), 3 months (P _ 0.0030), and 4 months (P _ 0.0046); the BILAG score after 1 month (P _ 0.029) and 3 months (P _0.009); and the FAS score after 2 months (P _ 0.0006) and 3 months (P _ 0.005). NAC increased __m (P _0.0001) in all T cells, profoundly reduced mTOR activity (P _ 0.0009), enhanced apoptosis (P _ 0.0004), reversed expansion of CD4_CD8_ T cells (mean _ SEM 1.35 _ 0.12-fold change; P _ 0.008), stimulated FoxP3 expression in CD4_CD25_ T cells (P _ 0.045), and reduced anti-DNA production (P _ 0.049)

 

Conclusion

This pilot study suggests that NAC safely improves lupus disease activity by blocking mTOR in T lymphocytes

 

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