Rosuvastatin ameliorates high‐fat and high‐cholesterol diet‐induced nonalcoholic steatohepatitis in rats

Okada, Yoshihisa; Yamaguchi, Kanji; Nakajima, Tomoki; Nishikawa, Taichiroh; Jo, Masayasu; Mitsumoto, Yasuhide; Kimura, Hiroyuki; Nishimura, Takeshi; Tochiki, Nozomi; Yasui, Kohichiroh; Mitsuyoshi, Hironori; Minami, Masahito; Kagawa, Keiichiro; Okanoue, Takeshi; Itoh, Yoshito

doi:10.1111/liv.12033

Cited by 57 publications

(51 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Simvastatin decreased hepatic inflammation and fibrosis through the inhibition of Ras and RhoA pathway, but without significant changes in steatosis or intrahepatic cholesterol content in a nonalcoholic steatohepatitis (NASH) mouse model [35]. In methionine-choline-deficient diet (MCDD) fed mice, statins have shown to prevent MCDD-induced NASH, restoring mitochondrial and peroxisomal fatty acid oxidation through attenuation of the decreased expression of peroxisomal proliferator-activated receptor α (PPARα) induced by NASH, independent of cholesterol levels [36, 37]. Rosuvastatin decreases free fatty acid liver content in high-fat high-cholesterol diet-induced NASH in rats, and reduces inflammatory markers (TNF-a, IL-6, ALT) and inflammation in histology [37].…”

Section: Pre-clinical Studies Of Statins In Liver Diseasementioning

confidence: 99%

Use of Statins in Patients with Chronic Liver Disease and Cirrhosis: Current Views and Prospects

Vargas

Arrese

Shah

et al. 2017

Curr Gastroenterol Rep

View full text Add to dashboard Cite

Purpose of review The purpose of this study is to analyze the current evidence regarding the use of statins in patients with chronic liver disease and cirrhosis. Recent findings Chronic liver disease (CLD), cirrhosis, and its complications, including hepatocellular carcinoma (HCC), are significant public health problems. The use of statins in patients with CLD has been a matter of concern, and physicians are often reluctant to its prescription in these patients. This mainly relates to the potential occurrence of drug-induced liver injury. However, newer evidence from pre-clinical and clinical research has shown that statins are drugs with a potentially beneficial impact on the natural history of cirrhosis, on portal hypertension, and in HCC prevention. Summary In this review, we summarize current evidence regarding the influence of statins in endothelial dysfunction in CLD, their ability to modulate hepatic fibrogenesis, and their vasoprotective effects in portal hypertension; we also focus on existing data about the impact of statins in cirrhosis development, progression, and complications and critically assess the current concerns about its use in patients with CLD.

show abstract

Section: Pre-clinical Studies Of Statins In Liver Diseasementioning

confidence: 99%

Use of Statins in Patients with Chronic Liver Disease and Cirrhosis: Current Views and Prospects

Vargas

Arrese

Shah

et al. 2017

Curr Gastroenterol Rep

View full text Add to dashboard Cite

show abstract

“…Similarly, in animal studies it has been reported that rosuvastatin ameliorates WD-induced liver steatosis in rats by decreasing TNF-α, IL-6, TGF-β and type-1 pro-collagen expression [40]. The reverse of WD-induced fibrotic NASH in obese, diabetic mice by atorvastatin is believed to be related to inactivation of JNK and reduction of hepatocyte apoptosis and inflammatory recruitment [41].…”

Section: Discussionmentioning

confidence: 99%

Activation of hepatic Nogo-B receptor expression—A new anti-liver steatosis mechanism of statins

Zhang

Yang

Chen

et al. 2018

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biolog

View full text Add to dashboard Cite

Deficiency of hepatic Nogo-B receptor (NgBR) expression activates liver X receptor α (LXRα) in an adenosine monophosphate-activated protein kinase α (AMPKα)-dependent manner, thereby inducing severe hepatic lipid accumulation and hypertriglyceridemia. Statins have been demonstrated non-cholesterol lowering effects including anti-nonalcoholic fatty liver disease (NAFLD). Herein, we investigated if the anti-NAFLD function of statins depends on activation of NgBR expression. In vivo, atorvastatin protected apoE deficient or NgBR floxed, but not hepatic NgBR deficient mice, against Western diet (WD)-increased triglyceride levels in liver and serum. In vitro, statins reduced lipid accumulation in nonsilencing small hairpin RNA-transfected Conflict of interestNone declared. Transparency documentThe http://dx.doi.org/10.1016/j.bbalip.2017.12.002 associated with this article can be found, in online version. HHS Public Access

show abstract

“…Some statins increase the adiponectin level, whichmaydecreaseFFAdeliverytotheliverandthus slowtheprogressionofsteatosis 128,139) .Arecentstudy demonstrated that atorvastatin therapy prevents dietinducedlipidaccumulationintheliveringuineapigs via the downregulation of hepatic CD36 proteins, which subsequently facilitates the hepatic uptake of lipids 140) . In a diet-induced fatty liver animal model, rosuvastatin was found to ameliorate hepatic fibrosis in association with a decrease in the hepatic mRNA expressionofTGF-β,connectivetissuegrowthfactor andtype-1procollagen 138) . Therefore,bothinvitroandinvivostudiessuggestthatstatinsplayaprotectiveroleinthedevelopmentandprogressionofNAFLDviavariousmechanisms.…”

Section: Effects Of Statins On Fatty Livermentioning

confidence: 99%

“…Atorvastatin improves the disease activity viaitsTNFα-loweringeffectsinbiopsy-provenNASH patients 137) , and rosuvastatin significantly ameliorates hepatic lobular inflammation by decreasing the hepaticmRNAexpressionofTNFαandIL6 138) . Some statins increase the adiponectin level, whichmaydecreaseFFAdeliverytotheliverandthus slowtheprogressionofsteatosis 128,139) .Arecentstudy demonstrated that atorvastatin therapy prevents dietinducedlipidaccumulationintheliveringuineapigs via the downregulation of hepatic CD36 proteins, which subsequently facilitates the hepatic uptake of lipids 140) .…”

Section: Effects Of Statins On Fatty Livermentioning

confidence: 99%

Antioxidant Effects of Statins in the Management of Cardiometabolic Disorders

Lim

Barter

2014

JAT

View full text Add to dashboard Cite

Redox systems are key players in vascular health. A shift in redox homeostasis-that results in an imbalance between reactive oxygen species (ROS) generation and endogenous antioxidant defenses has the potential to create a state of oxidative stress that subsequently plays a role in the pathogenesis of a number of diseases, including those of the cardiovascular and metabolic system. Statins, which are primarily used to reduce the concentration of low-density lipoprotein cholesterol, have also been shown to reduce oxidative stress by modulating redox systems.Studies conducted both in vitro and in vivo support the role of oxidative stress in the development of atherosclerosis and cardiovascular diseases. Oxidative stress may also be responsible for various diabetic complications and the development of fatty liver. Statins reduce oxidative stress by blocking the generation of ROS and reducing the NAD＋/NADH ratio. These drugs also have effects on nitric oxide synthase, lipid peroxidation and the adiponectin levels.It is possible that the antioxidant properties of statins contribute to their protective cardiovascular effects, independent of the lipid-lowering actions of these agents. However, possible adverse effects of statins on glucose homeostasis may be related to the redox system. Therefore, studies investigating the modulation of redox signaling by statins are warranted. J Atheroscler Thromb, 2014; 21:997-1010.

show abstract

Rosuvastatin ameliorates high‐fat and high‐cholesterol diet‐induced nonalcoholic steatohepatitis in rats

Abstract: These data suggest that rosuvastatin improved not only hepatic steatosis but also hepatic injury and fibrosis via improved peroxisomal β-oxidation in this rat HFHC model.

Cited by 57 publications

References 48 publications

Use of Statins in Patients with Chronic Liver Disease and Cirrhosis: Current Views and Prospects

Use of Statins in Patients with Chronic Liver Disease and Cirrhosis: Current Views and Prospects

Activation of hepatic Nogo-B receptor expression—A new anti-liver steatosis mechanism of statins

Antioxidant Effects of Statins in the Management of Cardiometabolic Disorders

Contact Info

Product

Resources

About