Increased Oxidative Stress and Mitochondrial Dysfunction in Zucker Diabetic XXXX Liver and Brain.

@entity6 @entity1506 @entity209 @entity164 @entity35 @entity2383
BACKGROUND/AIMS: The @entity6 ( @entity6 , FA/FA) @entity35 is a genetic model of @entity164 2 @entity6 , characterized by insulin resistance with progressive @entity209 . We have previously demonstrated @entity2383 and oxidative stress in the heart, kidneys and pancreas of @entity6 @entity35 . However, the precise molecular mechanism of disease progression is not clear. Our aim in the present study was to investigate oxidative stress and @entity2383 in the liver and brain of @entity6 @entity35 . METHODS: In this study, we have measured mitochondrial oxidative stress, bioenergetics and redox homeostasis in the liver and brain of @entity6 @entity35 . RESULTS: Our results showed increased reactive oxygen species (ROS) production in the @entity6 @entity35 brain compared to the liver, while nitric oxide (NO) production was markedly increased both in the brain and liver. High levels of lipid and protein peroxidation were also observed in these tissues. Glutathione metabolism and mitochondrial respiratory functions were adversely affected in @entity6 @entity35 when compared to Zucker lean (ZL, +/FA) control @entity35 . Reduced ATP synthesis was also observed in the liver and brain of @entity6 @entity35 . Western blot analysis confirmed altered expression of cytochrome P450 2E1, @entity1506 , p-JNK, and IkB-a confirming an increase in oxidative and metabolic stress in @entity6 @entity35 tissues. CONCLUSIONS: Our data shows that, like other tissues, @entity6 @entity35 liver and brain develop complications associated with redox homeostasis and @entity2383 . These results, thus, might have implications in understanding the etiology and pathophysiology of diabesity which in turn, would help in managing the disease associated complications.    2015 S. Karger AG, Basel.
