Resveratrol improves alcoholic fatty liver disease by downregulating HIF-1α expression and mitochondrial ROS production

Abstract

Oxidative stress has been demonstrated to be involved in the etiology of alcoholic fatty liver disease (AFLD). Previous studies had demonstrated that resveratrol (RES) could reduce oxidative stress by different mechanisms. However, the effect of RES on alcohol-induced fatty liver remains unclear. In the present study, a total of 48 male SD rats were divided into three groups: Control, AFLD, and RES groups. Rats were administered with either nothing or 65% vol/vol alcohol (5 ml/kg/day in the first three days, and then 10 ml/kg/day in the following days) with or without RES supplementation (250 mg/kg/day) for 4 weeks. Blood and liver tissue samples were collected and subjected to biochemical assays, histological examination, Western blot, and mitochondrial radical oxygen species (ROS) assays. In RES group, significant decreases in serum ALT and AST concentrations, fat deposition, triglyceride (TG) content, HIF-1α protein expression as well as mitochondrial ROS production in liver were observed when compared with AFLD group (all p <0.05). These results indicated that RES could alleviate the liver injury induced by alcohol and prevent the progression of AFLD. Down regulation of HIF-1α protein expression and mitochondrial ROS production in liver might be, at least part of, the underlying mechanisms.

Protective role of germinated mung bean against progression of non-alcoholic steatohepatitis in rats: A dietary therapy to improve fatty liver health

“…Furthermore we also observed increased mitochondrial ROS and serum nitrite/nitrate in steatosis and NASH animals. Recently Ma et al () also reported the similar findings in high fat diet fed animals.…”

“…ROS are generated during metabolic process of the cells, if it is unchecked by antioxidant defense system, cell will incline toward oxidative stress (Alcala et al, 2017;Lubos, Loscalzo, & Hand, 2011;Mortezaee & Khanlarkhani, 2017). In few conditions ROS could react with nitric oxide and generate higher reactive nitrogen species (RNS) known as peroxy nitrite (Chance, Sies, & Boveris, 1979;Hansen et al, 2016;Liochev & Fridovich, 2007 Recently Ma et al (2017) also reported the similar findings in high fat diet fed animals.…”

Health Benefits and Molecular Mechanisms of Resveratrol: A Narrative Review

“…Resveratrol also improved high-fat diet (HFD)-induced fatty liver by downregulating adipose differentiation-related proteins and increasing the numbers of CD68 + Kupffer cells [9]. As for chemical-induced liver diseases, resveratrol could markedly restore the morphology and function of alcohol-injured liver through inducing autophagy, or downregulating hypoxia-inducible factor 1α (HIF-1α) expression [85,86]. In addition, resveratrol ameliorated CCl 4 -induced liver injury by blocking the Notch signaling pathway [82].…”

“…In vivo Mice 0.2% of diet Improving HFD-induced fatty liver by downregulating adipose differentiation-related proteins and increasing the numbers of CD68 + Kupffer cells [9] In vivo Rats 10 mg/kg Attenuating hepatic fibrosis by restoring the architecture and normalizing collagen deposition, mainly due to its antioxidative activities and downregulation of α-SMA [80] In vivo Rats 50, 100 mg/kg Alleviating NAFLD by upregulating LDLR and SRB1 gene expressions [83] In vivo Rats 250 mg/kg/day Downregulating HIF-1α expression and mitochondrial ROS production [85] In vitro; In vivo HepG2 cells; Mice 45 µmol 10, 30, 100 mg/kg Restoring the morphology and function of alcohol-injured liver through inducing autophagy [86] In vivo Rats 10 mg/kg Mitigating liver cirrhosis by improving the homing of bone marrow-derived mesenchymal stem cells [87] Diabetes…”

Natural compounds in the chemoprevention of alcoholic liver disease

“…Hypoxia‐inducible factor‐1α (HIF‐1α) is an important determinant of lipid accumulation and alcoholic steatosis pathogenesis (Nath et al, ). Resveratrol was also reported to improve lipid accumulation in alcoholic liver injury by downregulating expression of HIF‐1α (Ma et al, ).…”