Olmesartan severely weakened the development of NASH in an animal model of hypercholesterolemia

“…PPAR-a in liver homogenate and low-density lipoprotein receptor (LDLR), high-sensitivity C-reactive protein (hs-CRP), and adiponectin (APN) were detected as well. [29][30][31] Also, the liver tissues of rats in each group were imaged by electron microscopy with hematoxylin-eosin as the staining agent.…”

Section: Introduction Rmentioning

confidence: 99%

Raspberry Ketone Protects Rats Fed High-Fat Diets Against Nonalcoholic Steatohepatitis

Wang

Meng

Zhang

2012

Journal of Medicinal Food

View full text Add to dashboard Cite

The protective effect of raspberry ketone against nonalcoholic steatohepatitis (NASH) was tested by using a high-fat diet-induced NASH model, and its mechanism was explored. Forty Sprague-Dawley rats with a 1:1 male to female ratio were randomly divided into five groups: the normal control (NC) group (n = 8) fed normal diet for 8 weeks, the model control (MC) group (n = 8) fed high-fat diet (82% standard diet, 8.3% yolk powder, 9.0% lard, 0.5% cholesterol, and 0.2% sodium taurocholate), and the raspberry ketone low-dose (0.5%) (RKL) group (n = 8), the raspberry ketone middle-dose (1%) (RKM) group (n = 8), and the raspberry ketone high-dose (2%) (RKH) group (n = 8) fed high-fat diet for 4 weeks. were measured in rats. Therefore, we determined the peroxisome proliferator-activated receptor (PPAR)-a activity in liver homogenate and the levels of low-density lipoprotein receptor (LDLR), high-sensitivity C-reactive protein (hs-CRP), adiponection (APN), superoxide dismutase, and malondialdehyde (MDA). The liver tissues of rats in each group were imaged by electron microscopy with hematoxylin-eosin as the staining agent. The levels of TG, TC, LDL-C, ALT, AST, ALP, GLU, INS, IRI, FFA, LEP, TNF-a, MDA, and hs-CRP of MC rats were significantly increased (P < .05, P < .01). Therefore, the levels of HDL-C, ISI, PPAR-a, LDLR, and APN were significantly decreased (P < .05, P < .01). Compared with the MC group, each parameter in the RKL, RKM, and RKH groups was significantly improved (P < .05, P < .01). Thus raspberry ketone was an effective intervention for NASH in rats. It was believed that raspberry ketone had a dual effect of liver protection and fat reduction, and the mechanism was probably mediated by alleviation of fatty degeneration of liver cells, decreased liver inflammation, correction of dyslipidemia, reversal of LEP and INS resistance, and improved antioxidant capacity.

show abstract

“…However, we demonstrated that the irbesartan significantly attenuated hepatic steatosis and reduced hepatic and plasma triglyceride levels, albeit not significant. Previous reports have shown that telmisartan and olmesartan also prevent steatosis in animal models of obesity in rats (19)(20)(21). AT-II infusion is known to stimulate hepatic triglyceride production in rats (22).…”

Section: Discussionmentioning

confidence: 99%

Therapeutic effects of angiotensin II type 1 receptor blocker, irbesartan, on non-alcoholic steatohepatitis using FLS-ob/ob male mice

et al. 2012

View full text Add to dashboard Cite

Abstract. Non-alcoholic steatohepatitis (NASH) is the hepatic manifestation of a metabolic syndrome characterized by accumulation of hepatic fat, inflammation and varying degrees of fibrosis. Angiotensin (AT)-II has been reported to play a role in the establishment of NASH. This study examined the effects of an AT-II receptor blocker, irbesartan, on NASH using fatty liver Shionogi (FLS)-ob/ob male mice as the closest animal model of human metabolic syndrome-related NASH. Irbesartan (30 mg/kg/day) was orally administered to FLS-ob/ob mice for 12 weeks (irbesartan group). The effects of irbesartan on steatohepatitis were examined using factors including steatosis, fibrosis, inflammation and oxidative stress. The areas of hepatic fibrosis and hepatic hydroxyproline content were significantly lower in the irbesartan group compared to controls. The areas of α-smooth muscle actin-positivity and F4/80-positive cells were significantly decreased in the irbesartan group. The percentage of 8-hydroxy-2-deoxyguanosine (8-OHdG)-positive cells and 8-OHdG DNA content were significantly decreased in the irbesartan group compared to controls. Levels of RNA expression for procollagen I, transforming growth factor β1, tumor necrosis factor-α, sterol regulatory element-binding protein 1c and fatty acid synthase were significantly lower in the irbesartan group compared to controls. In contrast, the gene expression of peroxisome proliferator activated receptor-α was significantly higher in the irbesartan group compared to controls. Irbesartan administration improved hepatic steatosis and attenuated the progression of hepatic fibrosis by inhibiting the activation of hepatic stellate cells and Kupffer cells and reducing oxidative stress. IntroductionNon-alcoholic steatohepatitis (NASH) is an advanced stage non-alcoholic fatty liver disease characterized by accumulation of hepatic fat, inflammation and varying degrees of fibrosis. NASH is the hepatic manifestation of a metabolic syndrome and is attracting attention as a major public health problem (1,2). The underlying metabolic abnormalities are related to the progression of liver injury, such as steatosis, necro-inflammation and fibrosis (3).The renin-angiotensin system (RAS) appears likely to play important roles in various aspects of the metabolic syndrome. For example, the activated RAS increases insulin resistance and oxidative stress (4). The RAS also influences fatty acid metabolism in the liver via activation of angiotensin (AT)-II type 1 receptor (ATR1) or AT type 2 receptor (ATR2) (5). Indeed, AT-II infusion stimulates hepatic triglyceride production and reduces insulin sensitivity (6). A local RAS has been recognized as acting in liver tissue and is reportedly upregulated by several experimental liver injuries (7,8). Blockade of the RAS attenuates hepatic inflammation and fibrosis by suppressing the activation of hepatic stellate cells (HSCs) and oxidative stress (8)(9)(10).Several investigations have demonstrated that AT-II receptor blockers (ARBs) improve insulin resistanc...

show abstract

Olmesartan severely weakened the development of NASH in an animal model of hypercholesterolemia

Cited by 27 publications

References 26 publications

The Role of Nuclear Receptors in the Pathophysiology, Natural Course, and Drug Treatment of NAFLD in Humans

The Role of Nuclear Receptors in the Pathophysiology, Natural Course, and Drug Treatment of NAFLD in Humans

Raspberry Ketone Protects Rats Fed High-Fat Diets Against Nonalcoholic Steatohepatitis

Therapeutic effects of angiotensin II type 1 receptor blocker, irbesartan, on non-alcoholic steatohepatitis using FLS-ob/ob male mice

Contact Info

Product

Resources

About