N-Acetylcysteine in hemodialysis diabetic patients resets the activation of NF-kB in lymphomonocytes to normal values.
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 delta AOPP as the dependent variable and delta p50-p50, delta TAC, and delta APO as independent variables, we found that all three dependent parameters all retained an independent correlation with delta 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.
Nephrology Dialysis Transplantation, Regina Margherita University Hospital, Torino, Italy. alessandro.amore@unito.it
Alessandro
A
Amore
Marco
M
Formica
Franca
F
Giacchino
Graziella
G
Gigliola
Franco
F
Bonello
Giovanni
G
Conti
Roberta
R
Camilla
Rosanna
R
Coppo
D000111:Acetylcysteine / Q000494:pharmacology*; D000368:Aged; D000369:Aged, 80 and over; D018592:Cross-Over Studies; D003928:Diabetic Nephropathies / Q000097:blood* / Q000628:therapy*; D005260:Female; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B / Q000187:drug effects* / Q000502:physiology*; D012016:Reference Values; D006435:Renal Dialysis
D016328:NF-kappa B; D000111:Acetylcysteine