The FXR agonist 6ECDCA reduces hepatic steatosis and oxidative stress induced by ethanol and low-protein diet in mice

Lívero, Francislaine Aparecida dos Reis; Stolf, Aline Maria; Dreifuss, Arturo Alejandro; Bastos-Pereira, Amanda Leite; Chicorski, Raphaella; Oliveira, Liana Gomes de; Souza, Carlos Eduardo Alves de; Fabossi, Isabella Aviles; Rabitto, I.S.; Gremski, Luiza Helena; Henneberg, Raílson; Telles, José Ederaldo Queiroz; Elferink, Ronald P.J. Oude; Acco, Alexandra

doi:10.1016/j.cbi.2014.03.014

Cited by 51 publications

(47 citation statements)

References 39 publications

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“…reported increasing levels of LPO in mice that developed steatosis after 6‐week feeding with 10% alcohol and a low‐protein diet. The same was observed with Cat and SOD activity, including increased levels of total ROS, indicating that oxidative stress contributed to the establishment of steatosis in that model . In a binge model, acute alcohol drinking also increased LPO and induced hepatic steatosis in mice.…”

Section: Pathogenesissupporting

confidence: 70%

Molecular basis of alcoholic fatty liver disease: From incidence to treatment

Lívero

Acco

2015

Hepatology Research

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Alcoholic liver diseases have complex and multiple pathogenic mechanisms but still no effective treatment. Steatosis or alcoholic fatty liver disease (AFLD) has a widespread incidence and is the first step in the progression to more severe stages of alcoholic liver disease, with concomitant increases in morbidity and mortality rates. The ways in which this progression occurs and why some individuals are susceptible are still unanswered scientific questions. Research with animal models and clinical evidence have shown that it is a multifactorial disease that involves interactions between lipid metabolism, inflammation, the immune response and oxidative stress. Each of these pathways provides a better understanding of the pathogenesis of AFLD and contributes to the development of therapeutic strategies. This review emphasizes the importance of research on alcoholic steatosis based on incidence data, key pathogenic mechanisms and therapeutic interventions, and discusses perspectives on the progression of this disease.

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Section: Pathogenesissupporting

confidence: 70%

Molecular basis of alcoholic fatty liver disease: From incidence to treatment

Lívero

Acco

2015

Hepatology Research

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“…The later not only exhausts mitochondrial antioxidant defender glutathione (GSH) but also activates Fas/FasL and the downstream apoptotic signaling pathway 93,94. Hepatocyte Fas expression was moderate to strong in ALD patients compared with only minimal Fas expression in control groups 90.…”

Section: Hepatocyte Apoptosis and Fatty Liver Diseasementioning

confidence: 99%

Mechanism of Hepatocyte Apoptosis

et al. 2016

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Hepatocyte apoptosis plays important roles in both the removal of external microorganisms and the occurrence and development of liver diseases. Different conditions, such as virus infection, fatty liver disease, hepatic ischemia reperfusion, and drug-induced liver injury, are accompanied by hepatocyte apoptosis. This review summarizes recent research on the mechanism of hepatocyte apoptosis involving the classical extrinsic and intrinsic apoptotic pathways, endoplasmic reticulum stress, and oxidative stress-induced apoptosis. We emphasized the major causes of apoptosis according to the characteristics of different liver diseases. Several concerns regarding future research and clinical application are also raised.

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“…The FXR activity was functionally impaired by chronic ethanol ingestion in a murine model of alcoholic liver disease [39] . In addition, the activation of FXR by its specific agonists, WAY-362450 or INT747, rescued the Acta Pharmacologica Sinica npg FXR activity, thereby attenuating the ethanol-induced hepatic liver injury, steatosis and cholestasis [39,40] . In addition, the activation of FXR was shown to protect against fructose-induced liver steatosis [41] , suggesting several diverse roles for FXR in …”

Section: Fxr In Hepatic Triglyceride Metabolismmentioning

confidence: 99%

Farnesoid X receptor: a master regulator of hepatic triglyceride and glucose homeostasis

Jiao¹,

Lu²,

Li³

2014

Acta Pharmacol Sin

155

127

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Non-alcoholic fatty liver disease (NAFLD) is characterized by the aberrant accumulation of triglycerides in hepatocytes in the absence of significant alcohol consumption, viral infection or other specific causes of liver disease. NAFLD has become a burgeoning health problem both worldwide and in China, but its pathogenesis remains poorly understood. Farnesoid X receptor (FXR), a member of the nuclear receptor (NR) superfamily, has been demonstrated to be the primary sensor for endogenous bile acids, and play a crucial role in hepatic triglyceride homeostasis. Deciphering the synergistic contributions of FXR to triglyceride metabolism is critical for discovering therapeutic agents in the treatment of NAFLD and hypertriglyceridemia.

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The FXR agonist 6ECDCA reduces hepatic steatosis and oxidative stress induced by ethanol and low-protein diet in mice

Abstract: Our data demonstrated that 6ECDCA reverses the accumulation of lipids in the liver and decreases the oxidative stress induced by ethanol and low-protein diet. This FXR agonist is promising as a potential therapy for alcoholic liver steatosis.

Cited by 51 publications

References 39 publications

Molecular basis of alcoholic fatty liver disease: From incidence to treatment

Molecular basis of alcoholic fatty liver disease: From incidence to treatment

Mechanism of Hepatocyte Apoptosis

Farnesoid X receptor: a master regulator of hepatic triglyceride and glucose homeostasis

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