Hepatic nitrosative stress in experimental diabetes.
OBJECTIVE
The effects of the inhibition of nitrosative stress by aminoguanidine in an experimental model of diabetes mellitus (DM) were investigated.


METHODS
Twenty-one male Wistar rats were divided into three groups: control (CO), diabetic (DM), and diabetic treated with aminoguanidine (DM+AG). Aminoguanidine (aminoguanidine hemisulfate salt, Sigma Chemical Co., St. Louis, MO, USA) was used at a dose of 50 mg/kg (i.p.) during the last 30 days of the experiment. The expression levels of liver lipoperoxidation (TBARS - nmol/mg protein), inducible oxide nitric synthase (iNOS), nitrotyrosine and the NFκB nuclear transcription factor p65 were examined using western blot analysis.


RESULTS
The DM group demonstrated an increase in lipoperoxidation and in the expression of iNOS, nitrotyrosine and p65. Aminoguanidine reduced hepatic lipid peroxidation and protein expression levels of iNOS, nitrotyrosine and p65.


CONCLUSIONS
Aminoguanidine treatment reduces liver oxidative and nitrosative stress in diabetic animals. In addition, aminoguanidine reduced the expression of p65 in the liver.
Laboratório de Fisiologia e Gastroenterologia Experimental, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul (UFRGS) 90035-903 Porto Alegre, RS, Brazil.
Fábio Cangeri
FC
Di Naso
Graziella
G
Rodrigues
Alexandre
A
Simões Dias
Marilene
M
Porawski
Henrique
H
Fillmann
Norma Possa
NP
Marroni
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy*; D015536:Down-Regulation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D006146:Guanidines / Q000627:therapeutic use*; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D008297:Male; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D026361:Reactive Nitrogen Species / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D051996:Transcription Factor RelA / Q000378:metabolism; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
D004791:Enzyme Inhibitors; D006146:Guanidines; D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species; C498145:Rela protein, rat; D051996:Transcription Factor RelA; C002744:3-nitrotyrosine; D014443:Tyrosine; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; C004479:pimagedine