Suppression of hepatic oxidative events and regulation of eNOS expression in the liver by naringenin in fructose-administered rats
Authors: Carani Venkatraman Anuradha
Nallasamy Palanisamy
Sriramajayam Kannappan
Journal: European Journal of Pharmacology (2010)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: naringenin; insulin sensitivity; oxidative damage; apoptosis; fructose-fed rats
Affiliations: Department of Biochemistry and Biotechnology, Annamalai University, Annamalai Nagar- 608 002, Tamil Nadu, India.

Abstract:  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 (50mg/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. 

Retracted: No

PubPeer comments:
 Fig. 4.  Immunohistochemcial localization of 2, 4-DNP in liver of experimental animals. **(4A) u2014 CON**; **(4B) u2014 FRU-fed rats**; (4C) u2014 fructose-fed rats treated with naringenin (50 mg kg b.w day); (4D) u2014 control rats treated with naringenin (50 mg kg b.w day).  Fig 4 from [Sumiyabanu et al (2009)] .  Immunohistochemistry for 3u2010nitrotyrosine (3u2010NT) protein adduct in liver sections from **genisteinu2010treated (d)** and untreated (a) controlu2010diet fed rats and genisteinu2010treated (c) and **untreated (b) high fructoseu2010fed rats** (original magnification u00d720). (b) Immunostaining for 3u2010NT is increased in the liver of fructoseu2010fed rats, but genistein treatment (c) prevents this increase. Both genisteinu2010treated (d) and untreated (a) controlu2010diet fed rats show negative staining for this antibody.  One slide appear in both papers illustrating the effect of a high-fructose diet, which is consistent, but another slide is either a Control or Genistein diet. Could the two groups of authors check? Inquiring readers might also like to know whether the immunohistochemistry related to 3u2010nitrotyrosine (3u2010NT) or to 2, 4-DNP. ,