Book ChapterDOI
Bile Acid-Induced Liver Injury in Cholestasis
Tiangang Li,John Y.L. Chiang +1 more
- pp 143-172
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TLDR
Bile acid biology, mechanism of cholestatic liver injury, and current and future bile acid-based therapeutics for cholESTasis are summarized.Abstract:
Bile acids are physiological detergent molecules synthesized from cholesterol exclusively in the hepatocytes. Bile acids play important roles in generating bile flow and facilitating intestinal nutrient absorption. Bile acids are endogenous ligands of nuclear receptors and cell surface G protein-coupled receptors, which regulate various biological processes including metabolism, immune response, and cell proliferation. Cholestasis is a pathological condition where bile flow out of the liver is reduced or blocked, leading to accumulation of bile acids, cell death, and inflammation in the liver. Chronic cholestasis leads to liver fibrosis, cirrhosis, failure, and carcinogenesis. During cholestasis, bile acid-activated signaling regulates bile acid detoxification mechanisms as well as cell survival and proliferation. The hydrophilic bile acid UDCA has been used as the primary cholestasis therapy for decades. Pharmacological agents targeting the bile acid receptors are being developed as novel therapeutics for cholestasis. This chapter summarizes bile acid biology, mechanism of cholestatic liver injury, and current and future bile acid-based therapeutics for cholestasis.read more
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Journal ArticleDOI
Betaine treatment protects liver through regulating mitochondrial function and counteracting oxidative stress in acute and chronic animal models of hepatic injury
Reza Heidari,Hossein Niknahad,Ala Sadeghi,Hamidreza Mohammadi,Vahid Ghanbarinejad,Mohammad Mehdi Ommati,Arghavan Hosseini,Negar Azarpira,Forouzan Khodaei,Omid Farshad,Elaheh Rashidi,Asma Siavashpour,Asma Najibi,Asrin Ahmadi,Akram Jamshidzadeh +14 more
TL;DR: Betaine supplementation ameliorated hepatic injury as judged by decreased liver tissue histopathological alterations, a significant decrease in tissue markers of oxidative stress, and mitigation of serum biomarkers of hepatotoxicity.
Journal ArticleDOI
Cholestasis-associated reproductive toxicity in male and female rats: The fundamental role of mitochondrial impairment and oxidative stress.
Mohammad Mehdi Ommati,Omid Farshad,Hossein Niknahad,Mohammad Reza Arabnezhad,Negar Azarpira,Hamid Mohammadi,Maral Haghnegahdar,Khadijeh Mousavi,Shiva Akrami,Akram Jamshidzadeh,Reza Heidari +10 more
TL;DR: Evaluated pathologic effects of cholestasis-associated reproductive toxicity in male and female rats is restrictedly coupled with severe oxidative stress and mitochondrial impairment.
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Mitochondrial dysfunction as a mechanism involved in the pathogenesis of cirrhosis-associated cholemic nephropathy.
Reza Heidari,Leila Mandegani,Vahid Ghanbarinejad,Asma Siavashpour,Mohammad Mehdi Ommati,Negar Azarpira,Asma Najibi,Hossein Niknahad +7 more
TL;DR: Mitochondrial dysfunction and energy metabolism disturbances are introduced as a fundamental mechanism involved in the pathogenesis of bile acids-associated renal injury during cholestasis.
Journal ArticleDOI
N-acetyl cysteine treatment mitigates biomarkers of oxidative stress in different tissues of bile duct ligated rats.
Mohammad Mehdi Ommati,Ali Amjadinia,Khadijeh Mousavi,Negar Azarpira,Akram Jamshidzadeh,Reza Heidari +5 more
TL;DR: It was found that NAC treatment significantly mitigated biomarkers of oxidative stress and alleviated tissue histopathological changes in cirrhotic rats, representing NAC as a potential protective agent with therapeutic capability in cholestasis and its associated complications.
Journal ArticleDOI
Hormonal Contribution to Liver Regeneration.
TL;DR: This review article comprehensively summarize the current knowledge regarding the roles and mechanisms of these hormones in liver regeneration and believes that these endocrinal hormones are important hepatic mitogens that strongly induce and accelerate hepatocyte proliferation (regeneration) by directly and indirectly triggering the activity of the involved signaling pathways, cytokines, growth factors, and transcription factors.
References
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Journal ArticleDOI
Cloning and molecular characterization of the ontogeny of a rat ileal sodium-dependent bile acid transporter.
Benjamin L. Shneider,Paul A. Dawson,Donna M. Christie,Winita Hardikar,Melissa H. Wong,Frederick J. Suchy +5 more
TL;DR: The developmental regulation of the rat ileal sodium-dependent bile acid cotransporter is characterized by transcriptionally regulated increases in mRNA and protein levels at the time of weaning with changes in apparent molecular weight of the protein after weaning.
Journal ArticleDOI
Hepatic transport of bile salts
TL;DR: The hepatocyte can regulate expression levels of individual bile salt transporters during cholestasis to evade hepatotoxic injury, and is a vulnerable target for inhibition by estrogen metabolites, drugs such as cyclosporine A, and abnormal bile Salt metabolites, all of which can cause retention of bile salts and consequently intrahepatic cholESTasis.
Journal ArticleDOI
Complex inheritance of familial hypercholanemia with associated mutations in TJP2 and BAAT.
Victoria E.H. Carlton,Baruch Z. Harris,Erik G. Puffenberger,Ashok K. Batta,A. S. Knisely,Donna L. Robinson,Kevin A. Strauss,Benjamin L. Shneider,Wendell A. Lim,Gerald Salen,D. Holmes Morton,Laura N. Bull +11 more
TL;DR: It is shown here that FHC in Amish individuals is associated with mutations in tight junction protein 2 (encoded by TJP2) and bile acid Coenzyme A: amino acid N-acyltransferase (encoding by BAAT).
Journal ArticleDOI
Liver-specific Activities of FGF19 Require Klotho beta
TL;DR: KLB is defined as a novel FGFR4 coreceptor required for FGF19 liver specific functions, and is shown to be widely distributed in mouse, whereas KLB distribution is more restricted.
Journal ArticleDOI
The G‐protein coupled bile salt receptor TGR5 is expressed in liver sinusoidal endothelial cells
Verena Keitel,Roland Reinehr,Petros Gatsios,C. Rupprecht,Boris Görg,Oliver Selbach,Dieter Häussinger,Ralf Kubitz +7 more
TL;DR: The data suggest that SEC are directly responsive toward specific bile salts, and Regulation of eNOS in SEC by TGR5 connects bile salt with hepatic hemodynamics, of particular importance in cholestatic livers when bile Salt concentrations are increased.