Effects of N-acetylcysteine on nicotinamide dinucleotide phosphate oxidase activation and antioxidant status in heart, lung, liver and kidney in streptozotocin-induced diabetic rats.
OBJECTIVE
Hyperglycemia increases reactive oxygen species (ROS) and the resulting oxidative stress plays a key role in the pathogenesis of diabetic complications. Nicotinamide dinucleotide phosphate (NADPH) oxidase is one of the major sources of ROS production in diabetes. We, therefore, examined the possibility that NADPH oxidase activation is increased in various tissues, and that the antioxidant N-acetylcysteine (NAC) may have tissue specific effects on NADPH oxidase and tissue antioxidant status in diabetes.


METHODS
Control (C) and streptozotocin-induced diabetic (D) rats were treated either with NAC (1.5 g/kg/day) orally or placebo for 4 weeks. The plasma, heart, lung, liver, kidney were harvested immediately and stored for biochemical or immunoblot analysis.


RESULTS
levels of free 15-F(2t)-isoprostane were increased in plasma, heart, lung, liver and kidney tissues in diabetic rats, accompanied with significantly increased membrane translocation of the NADPH oxidase subunit p67phox in all tissues and increased expression of the membrane-bound subunit p22phox in heart, lung and kidney. The tissue antioxidant activity in lung, liver and kidney was decreased in diabetic rats, while it was increased in heart tissue. NAC reduced the expression of p22phox and p67phox, suppressed p67phox membrane translocation, and reduced free 15-F(2t)-isoprostane levels in all tissues. NAC increased antioxidant activity in liver and lung, but did not significantly affect antioxidant activity in heart and kidney.


CONCLUSIONS
The current study shows that NAC inhibits NADPH oxidase activation in diabetes and attenuates tissue oxidative damage in all organs, even though its effects on antioxidant activity are tissue specific.
Department of Pharmacology, School of Basic Medical Science, Wuhan University, Wuhan, Hubei Province, 430072, China.
Shaoqing
S
Lei
Yanan
Y
Liu
Huimin
H
Liu
Hong
H
Yu
Hui
H
Wang
Zhengyuan
Z
Xia
D000111:Acetylcysteine / Q000627:therapeutic use*; D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000378:metabolism*; D006321:Heart / Q000187:drug effects; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D008297:Male; D019255:NADPH Oxidases / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000975:Antioxidants; D019255:NADPH Oxidases; D000111:Acetylcysteine