Research article

Resveratrol inhibits nonalcoholic fatty liver disease in rats

Luis Bujanda¹ , Elizabeth Hijona¹ , Mikel Larzabal² , Marta Beraza¹ , Pablo Aldazabal³ , Nerea García-Urkia³ , Cristina Sarasqueta⁴ , Angel Cosme¹ , Belen Irastorza⁵ , Alberto González⁶ and Juan I Arenas Jr¹

¹Department of Gastroenterology, University of Country Basque, Donostia Hospital, Centro de Investigación Biomédica en Enfermedades Hepáticas y Digestivas (CIBERehd), San Sebastián, Spain

²Department of Pathology, Donostia Hospital, San Sebastián, Spain

³Department of Experimental Surgery, Donostia Hospital, San Sebastián, Spain

⁴Department of Epidemiology, Donostia Hospital, San Sebastián, Spain

⁵Department of Pharmacology, Donostia Hospital, San Sebastián, Spain

⁶Department of Microbiology, Donostia Hospital, San Sebastián, Spain

author email corresponding author email

BMC Gastroenterology 2008, 8:40doi:10.1186/1471-230X-8-40

Published:	9 September 2008

Abstract

Background

The prevalence of nonalcoholic fatty liver disease (NAFLD) is high. NAFLD is linked to obesity, diabetes mellitus, and hypertriglyceridemia. Approximately 20% of patients with NAFLD will eventually develop cirrhosis. Our purpose was to investigate whether resveratrol decreased hepatic steatosis in an animal model of steatosis, and whether this therapeutic approach resulted in a decrease in tumor necrosis factor α (TNF-α) production, lipid peroxidation and oxidative stress.

Methods

Male Wistar CRL: Wi (Han) (225 g) rats were randomized into three groups. A control group (n = 12) was given free access to regular dry rat chow for 4 weeks. The steatosis (n = 12) and resveratrol (n = 12) groups were given free access to feed (a high carbohydrate-fat free modified diet) and water 4 days per week, and fasted for the remaining 3 days for 4 weeks. Rats in the resveratrol group were given resveratrol 10 mg daily by the oral route. All rats were killed at 4 weeks and assessed for fatty infiltration and bacterial translocation. Levels of TNF-α in serum, hepatic malondialdehyde (MDA), oxidative stress (superoxide dismutase, glutathione peroxidase, catalase and nitric oxide synthase) and biochemical parameters were measured.

Results

Fat deposition was decreased in the resveratrol group as compared to the steatosis group (Grade 1 vs Grade 3, P < 0.05). TNF-α and MDA levels were significantly increased in the steatosis group (TNF-α; 33.4 ± 5.2 vs 26.24 ± 3.47 pg/ml and MDA; 9.08 ± 0.8 vs 3.17 ± 1.45 μM respectively, P < 0.05). This was accompanied by increased superoxide dismutase, glutathione peroxidase and catalase and decreased nitric oxide synthase in the liver of resveratrol group significantly (P < 0.05 vs steatosis group). Bacterial translocation was not found in any of the groups. Glucose levels were decreased in the group of rats given resveratrol (P < 0.05).

Conclusion

Resveratrol decreased NAFLD severity in rats. This effect was mediated, at least in part, by TNF-α inhibition and antioxidant activities.