Suppression of hepatic oxidative events and regulation of eNOS expression in the liver by naringenin in fructose-administered rats
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- 作者：Sriramajayam Kannappan ; Nallasamy Palanisamy ; Carani Venkatraman Anuradha
- 关键词：Naringenin ; Nitroxidative stress ; Nitric oxide ; Flavonoid ; Antioxidant ; L-NAME
- 刊名：European Journal of Pharmacology
- 出版年：2010
- 出版时间：25 October 2010
- 年：2010
- 卷：645
- 期：1-3
- 页码：177-184
- 全文大小：1138 K
文摘
Previous studies show that naringenin promotes insulin sensitivity in fructose-fed rats. This study investigates whether naringenin prevents oxidative events and apoptotic changes triggered in the rat liver by a high fructose diet. Male Wistar rats of body weight 150–180 g were fed either diet containing starch (60 % carbohydrate) or fructose (60 % fructose diet). From the 16th day of feeding, rats in each dietary group were divided into two, and treated or not with naringenin (50 mg/kg b.w/day). After 60 days, oxidative and nitrosative damage and endothelial nitric oxide synthase (eNOS) expression and hepatocyte apoptosis were determined. To evaluate whether nitric oxide (NO) plays a role in naringenin action, insulin sensitivity indices, fasting plasma glucose and insulin were assessed in response to co-administration of l-nitro-arginine methyl ester (L-NAME), a NOS inhibitor. Fructose feeding caused oxidative damage to proteins and lipids and resulted in reduced antioxidant status, eNOS expression and nitrite level. Increased formation of 4-hydroxy nonenal (4-HNE), 2, 4-dinitrophenol (2, 4-DNP) and 3-nitrotyrosine (3-NT)-modified proteins and the presence of apoptotic nuclei were observed in the liver. Treatment with naringenin attenuated all these parameters to levels not significantly different from control. Treatment with naringenin improved insulin sensitivity. However, L-NAME plus naringenin administration abolished the insulin-sensitizing effects of naringenin in fructose-fed rats. Reduced oxidative events with simultaneous increase in NO bioavailability may be involved in the insulin-sensitizing and cytoprotective effects of naringenin in fructose-fed rats.