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Aberrant liver sirtuin 1 (SIRT1), a mammalian NAD-dependent protein deacetylase, is implicated in the pathogenesis of alcoholic liver disease. However, the role of intestinal SIRT1 in alcoholic liver disease is presently unknown. This study investigated the involvement of intestine-specific SIRT1 in ethanol-induced liver dysfunction in mice. Ethanol feeding studies were performed on knockout mice with intestinal specific SIRT1 deletion (SIRT1iKO) and flox control (WT) mice with a chronic-plus-binge ethanol feeding protocol. Following ethanol administration, hepatic inflammation and liver injury were substantially attenuated in the SIRT1iKO mice compared to WT mice, suggesting that intestinal SIRT1 played a detrimental role in the ethanol-induced liver injury. Mechanistically, the hepatic protective effect of intestinal SIRT1 deficiency was attributable to ameliorated dysfunctional iron metabolism, increased hepatic glutathione contents, and attenuated lipid peroxidation, along with normalization of a panel of genes implicated in the ferroptosis process in the livers of ethanol-fed mice. This study demonstrates that ablation of intestinal SIRT1 protected mice from the ethanol-induced inflammation and liver damage. The protective effects of intestinal SIRT1 deficiency are mediated, at least partially, by mitigating hepatic ferroptosis. Targeting intestinal SIRT1 or dampening hepatic ferroptosis signaling may have therapeutic potential for alcoholic liver disease in humans.
This article was published in the following journal.
Name: The American journal of pathology
In the present study, we aimed to investigate the therapeutic effect of Vitexin on inhibiting ethanol-induced liver damage and explore the underling mechanism. In vitro, the injury was induced in LO2 ...
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The aime of this study is to envsitigate if ethanol has an incretin effect. This is done by administration of ethanol orally vs. an isoethanolaemic i.v. infusion of ethanol.
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Systemic and Local Diffusion of Ethanol After Administration of Ethanol 96% Formulated in a Gel and Ethanol 98% Solution by the Percutaneous Route, in Patients With Congenital Venous Malformations:Pharmacokinetic, Pharmacodynamic and Clinical Study.
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A condition caused by the lack of intestinal PERISTALSIS or INTESTINAL MOTILITY without any mechanical obstruction. This interference of the flow of INTESTINAL CONTENTS often leads to INTESTINAL OBSTRUCTION. Ileus may be classified into postoperative, inflammatory, metabolic, neurogenic, and drug-induced.
A strain of ENCEPHALOMYOCARDITIS VIRUS, a species of CARDIOVIRUS, usually causing an inapparent intestinal infection in mice. A small number of mice may show signs of flaccid paralysis.
Species of GAMMARETROVIRUS, containing many well-defined strains, producing leukemia in mice. Disease is commonly induced by injecting filtrates of propagable tumors into newborn mice.
A nutritional condition produced by a deficiency of THIAMINE in the diet, characterized by anorexia, irritability, and weight loss. Later, patients experience weakness, peripheral neuropathy, headache, and tachycardia. In addition to being caused by a poor diet, thiamine deficiency in the United States most commonly occurs as a result of alcoholism, since ethanol interferes with thiamine absorption. In countries relying on polished rice as a dietary staple, BERIBERI prevalence is very high. (From Cecil Textbook of Medicine, 19th ed, p1171)
Strains of mice arising from a parental inbred stock that was subsequently used to produce substrains of knockout and other mutant mice with targeted mutations.
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