Cardiovascular protective effect of pioglitazone on oxidative stress in rats with metabolic syndrome.

BACKGROUND: Although cardiovascular oxidative stress is examined in type 2 diabetes, there is relatively limited number of reports about the effect of pioglitazone, an insulin sensitizer, on cardiovascular oxidative stress in sucrose diet-induced metabolic syndrome (MetS). As a regulator of cardiovascular homeostasis, thioredoxin (TRX) has an important role in defense against oxidative stress in cardiovascular diseases. The purpose of this study is to investigate the role of pioglitazone on oxidative stress markers and TRX1 level in tissues of both heart and aorta from MetS rats.

METHODS: Male Wistar rats (200 to 250 g in weight) were divided into three groups: control group, MetS group receiving drinking water including 935 mM sucrose, and pioglitazone-treated MetS (MetS-P) group. Aspartate aminotransferase (AST), lactate dehydrogenase (LDH), total oxidant status (TOS), and total antioxidant status (TAS) levels were measured in serum and tissues using commercial kits. Malondialdehyde (MDA) and superoxide dismutase (SOD) were measured in serum and tissues for experimental groups. TRX1 protein level was measured by western blot.

RESULTS: The sucrose-fed rats exhibited several characteristics of MetS. In MetS group, AST, LDH, TOS, and MDA levels of heart and aorta tissues increased, whereas TAS and SOD levels of these tissues decreased. TRX1 protein level of heart and aorta tissues decreased in MetS group. Also, in the serum of experimental groups, AST, LDH, and TOS levels increased.

CONCLUSION: Pioglitazone treatment significantly increased TRX1 protein level in heart and aorta tissues in MetS group. Pioglitazone affected the TRX1 protein level via regulation of reactive oxygen intermediates. Pioglitazone reduced the elevated oxidative stress in heart and aorta of MetS rats.