Genistein improves liver function and attenuates non-alcoholic fatty liver disease in a rat model of insulin resistance
Authors: Anuradha Carani Venkatraman
Sumiyabanu Mohamed Salih
Palanisamy Nallasamy
Pooranaperundevi Muniyandi
Viswanathan Periyasami
Journal: Journal of diabetes (2009)
Discipline: CLINICAL MEDICINE
Keywords: fructose-fed rat; insulin resistance; genistein; fatty liver disease; Wistar rats
Affiliations: Department of Biochemistry and Biotechnology, Rajah Muthiah Medical College, Annamalai University, Annamalai Nagar, Tamil Nadu, India.

Abstract:  Background: The high fructose-fed rat is widely used as a model of insulin resistance. Genistein, a soy isoflavone, has been shown to improve insulin sensitivity in this model. The present study investigated whether genistein could prevent fatty liver disease in this model. Methods: Male Wistar rats were fed a diet containing starch (control) or 60% fructose (insulin-resistant model). Fifteen days later, rats in each dietary group were divided into two groups and were treated with either genistein (1 mg/kg per day) in dimethylsulfoxide (DMSO) or 30% DMSO alone. After 60 days, markers of liver injury, oxidative stress, interleukin (IL)-6, tumor necrosis factor (TNF)-α, lipids, lipoprotein profile, nitrite, and nitrosothiol in the plasma and liver were quantified. Liver sections were examined for 3-nitrotyrosine (3-NT) expression and pathological lesions. Results: Fructose-fed rats displayed hyperlipidemia, significant changes in plasma lipoprotein profile, and increases in IL-6 and TNF-α levels compared with control. In addition, the accumulation of lipids, liver injury, a decline in liver function, inactivation of the glyoxalase system, depletion of antioxidants, and increased 3-NT expression were observed in the fructose-fed group. Administration of genistein to fructose-fed rats significantly reduced these biochemical and histological abnormalities. Conclusions: Genistein activates the antioxidant profile, decreases IL-6 and TNF-α concentrations, prevents oxidative damage, and ameliorates fatty liver in insulin-resistant rats. 

Retracted: Yes

PubPeer comments:
 Fig 4.  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. ![file] Fig. 4 from [Kannappan et al (2010)] .  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). ![file] One slide appears 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. , 
 we will look into it , 
 Retracted [17 March 2022] .  The above article, first published online on October 27, 2009 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the Editors-in-Chief, Zachary T. Bloomgarden and Guang Ning, Ruijin Hospital, Shanghai Jiaotong University School of Medicine and John Wiley Sons Australia, Ltd. The retraction has been agreed as Figure 4 was found to have been published in another article (Suppression of hepatic oxidative events and regulation of eNOS expression in the liver by naringenin in fructose-administered rats. *Eur J Pharmacol*. 2010 Oct 25;645[1-3]:177u2013184) by the same group of authors but purporting to show different results. The authors were unable to provide a satisfactory explanation and did not provide the data used in creating the Figure. Furthermore, the Editors, along with an additional reviewer, have been unable to confirm that Figure 4 supports the results and conclusions of the article. Based on this, the Editors hereby retract the article.  ,