N-Acetylcysteine in hemodialysis diabetic patients resets the activation of NF-kB in lymphomonocytes to normal values

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Abstract

Background:

Oxidative stress pathways are activated in diabetes, particularly when dialysis is required (DD). NF-kB is activated in this clinical condition. Since N-Acetyl-cysteine (NAC) is an anti-oxidant, we aimed at investigating its effect in modulating NF-kB activation in lymphomonocytes (PBMC) of DD patients.

Methods:

Twenty-five DD patients were enrolled in a cross-over designed study. Tests were performed at T0 and after one month (T1) of treatment with NAC and three months after NAC withdrawal. We assessed NF-kB activation by EMSA, levels of advanced oxidation protein products (AOPP) by spectral analysis, total antioxidant capacity (TAC) by colorimetry, and apoptosis by FACS.

Results:

At T0 a statistically significant increased activation of the subunits of NF-kB, p50/p65, was detected in PBMC of DD patients in comparison to controls (both P<.0001). After one month of NAC both p50-p50/p50-p65 dimers were significantly reduced (P<.004 and .006). Three months after drug withdrawal NF-kB increased again to basal levels (P<.002 and P<.001 vs. end of treatment with NAC). AOPP and TAC levels and the percentage of apoptotic PBMC revealed modifications in accordance with NFkB activation. In a multivariate linear regression model using Δ AOPP as the dependent variable and Δ p50-p50, Δ TAC, and Δ APO as independent variables, we found that all three dependent parameters all retained an independent correlation with Δ AOPP.

Conclusions:

Our data indicate in vivo a modulation by NAC of parameters indicating a redox imbalance in DD patients on hemodialysis. The use of NAC might suggest a potential clinical benefit.

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