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Effect of genistein on expression of pancreatic SIRT1, inflammatory cytokines and histological changes in ovariectomized diabetic rat.

ABSTRACT: Genistein is reported to have anti-diabetic and anti-inflammatory functions, in particular, direct effects on β-cell proliferation and insulin secretion. In this study, we investigated the anti-inflammatory effect of genistein on the pancreatic β-cells in ovariectomized diabetic rat.Forty female rats were divided into four groups: sham, bilateral ovariectomy (OVX), OVX.D (OVX+diabetes) and OVX.D.G (OVX.D+genistein). After bilateral ovariectomy, rats in the diabetic groups were fed high-fat diet (HFD), ad libitum for 4 weeks, and then a low dose of streptozotocin (STZ) (30 mg/kg) injected intraperitoneally. Genistein (1 mg/kg/day; SC) was administrated for 8 weeks. At the end of 8 weeks, pancreas tissue was removed and used for western blotting and Hematoxylin-Eosin staining.Treatment with genistein declined inflammation and tissue injury, and this decline was correlated with the expression of SIRT1. OVX and OVX.D significantly increased Nf-κB and IL-1β expression and decreased SIRT1 levels compared to sham group (P<0.05). Significant reduction of Nf-κB and IL-1β, and increasing of SIRT1 were observed during genistein treatment (P<0.05).Estrogen deficiency alone or with HFD increased pancreatic inflammation. However, subcutaneous administration of gtenistein prevented from these inflammatory changes in the pancreas of a surgery animal model of ovariectomy with or without diabetes. Our results support the potential preventing effect of genistein from pancreatic injury.

SUBMITTER: Yousefi H

PROVIDER: S-EPMC5425925 | biostudies-other | 2017 Apr

REPOSITORIES: biostudies-other

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Project description:Background:The prevalence of nonalcoholic steatohepatitis (NASH) in menopausal women is increasing, but current treatments have not been proven effective. The objective of this study was to investigate the treatment effects of genistein and running exercise in ovariectomized (OVX) rats with NASH.Methods:Thirty-six female Sprague-Dawley rats were divided into 6 groups, control; OVX with standard diet; OVX with high fat and high fructose (HFHF) diet for 4?weeks; OVX with HFHF and genistein treatment (16?mg/kg BW/day) for 5?weeks (OVX?+?HFHF+GEN); OVX with HFHF and moderate intensity exercise for 5?weeks (OVX?+?HFHF+EX); OVX with HFHF and combined treatments (OVX?+?HFHF+GEN?+?EX). Serum interleukin-6 (IL-6) levels, hepatic free fatty acid (FFA), hepatic glutathione (GSH), and hepatic malondialdehyde (MDA) levels were measured. Liver histology was examined to determine NASH severity.Results:OVX?+?HFHF group had the highest levels of hepatic FFA compared with OVX and control groups (5.92?±?0.84 vs. 0.37?±?0.01 vs. 0.42?±?0.04?nmol/mg protein, respectively, p?<?0.01). Serum IL-6 levels were significantly elevated in both OVX and OVX?+?HFHF groups as compared with controls (112.13?±?6.50 vs. 121.47?±?3.96 vs. 86.13?±?2.40?pg/mL, respectively, p?<?0.01). In OVX?+?HFHF group, hepatic MDA levels were higher, while GSH levels were lower than in OVX and control groups (MDA; 0.98?±?0.04 vs. 0.82?±?0.02 vs. 0.78?±?0.03?nmol/mg protein, and GSH; 46.01?±?0.91 vs. 55.21?±?1.40 vs. 57.94?±?0.32, respectively; p?<?0.01 for both). Comparing with OVX?+?HFHF group, rats that received genistein, exercise and combined treatments demonstrated an improvement in liver histopathology, decreased levels of hepatic FFA (1.44?±?0.21 vs. 0.45?±?0.04 vs. 0.49?±?0.05?nmol/mg protein, respectively, p?<?0.01), serum IL-6 (82.80?±?2.07 vs. 83.47?±?2.81 vs. 94.13?±?1.61?pg/mL, respectively, p?<?0.01), and hepatic MDA (0.80?±?0.03 vs. 0.76?±?0.02 vs. 0.76?±?0.03?nmol/mg protein, respectively, p?<?0.01).Conclusions:Genistein and moderate intensity exercise were effective in reducing the severity of NASH in OVX rats through the reduction in liver inflammation, oxidative stress and liver fat contents.

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Effect of genistein on expression of pancreatic SIRT1, inflammatory cytokines and histological changes in ovariectomized diabetic rat.

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