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.
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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.
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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.
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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
The receptor TGR5 mediates the prokinetic actions of intestinal bile acids and is required for normal defecation in mice
Farzad Alemi,Daniel P. Poole,Jonathon V. Chiu,Kristina Schoonjans,Fiore Cattaruzza,John R. Grider,Nigel W. Bunnett,Carlos U. Corvera,Carlos U. Corvera +8 more
TL;DR: The receptor TGR5 mediates the effects of BAs on colonic motility, and deficiency of Tgr5 causes constipation in mice, and TGR 5 might be a therapeutic target for digestive diseases.
Journal Article
Identification of a sister gene to P-glycoprotein
TL;DR: A novel gene closely related to the Pgps expressed in the pig and other mammalian liver is identified which is called Sister of P-glycoprotein (spgp), and sequence of this gene shows it to be a member of the ATP-binding cassette family of transporters and the gene most closelyrelated to Pgp identified to date.
Journal ArticleDOI
Conjugated bile acids activate the sphingosine-1-phosphate receptor 2 in primary rodent hepatocytes.
Elaine Studer,Xiqiao Zhou,Renping Zhao,Yun Wang,Kazuaki Takabe,Masayuki Nagahashi,William M. Pandak,Paul Dent,Sarah Spiegel,Ruihua Shi,Weiren Xu,Xuyuan Liu,Pat Bohdan,Luyong Zhang,Huiping Zhou,Phillip B. Hylemon +15 more
TL;DR: All these data support the hypothesis that conjugated bile acids activate the ERK1/2 and AKT signaling pathways primarily through S1P2 in primary rodent hepatocytes.
Journal ArticleDOI
Liver receptor homologue-1 mediates species- and cell line-specific bile acid-dependent negative feedback regulation of the apical sodium-dependent bile acid transporter
Frank Chen,Lin Ma,Paul A. Dawson,Christopher J. Sinal,Ephraim Sehayek,Frank J. Gonzalez,Jan L. Breslow,Meenakshisundaram Ananthanarayanan,Benjamin L. Shneider +8 more
TL;DR: Cell line- and species-specific negative feedback regulation of ASBT by bile acids is mediated by farnesoid X receptor via small heterodimer partner-dependent repression of LRH-1 activation of the ASBT promoter.
Journal ArticleDOI
Effect of side-chain shortening on the physiologic properties of bile acids: Hepatic transport and effect on biliary secretion of 23-nor-ursodeoxycholate in rodents
TL;DR: It is proposed that a fraction of nor-UDC is secreted into canalicular bile in the unconjugated form and is protonated by a hydrogen ion derived from carbonic acid that was generated by the hydration of luminal CO2 by carbonic anhydrase present in biliary ductular cells.