Resveratrol inhibits nonalcoholic fatty liver disease in rats

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 alpha (TNF-alpha) 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-alpha 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-alpha and MDA levels were significantly increased in the steatosis group (TNF-alpha; 33.4 +/- 5.2 vs 26.24 +/- 3.47 pg/ml and MDA; 9.08 +/- 0.8 vs 3.17 +/- 1.45 muM 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-alpha inhibition and antioxidant activities.

Figure 1

NAFLD model used in the study.

Figure 2

Histological study in the different groups (control, steatosis, and resveratrol). Thus, the control group is shown to have no fat vacuoles. A great number of vacuoles were seen in the steatosis group, while the resveratrol group had much less vacuoles of a lower size. Hematoxylin and eosin staining of liver tissue × 40.

Figure 3

TNF-α and MDA levels. A. TNF-α levels in differents groups (pg/mL). TNF-α levels were lower in the resveratrol groups as compared to the control and steatosis groups. B. Levels of MDA in differents groups (μM). MDA levels were lower in the resveratrol groups as compared to the steatosis group (*P < 0.05).