Book ChapterDOI
Bile Acid-Induced Liver Injury in Cholestasis
Tiangang Li,John Y.L. Chiang +1 more
- pp 143-172
Reads0
Chats0
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
Citations
More filters
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.
Journal ArticleDOI
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
More filters
Journal ArticleDOI
Ligand-activated Pregnane X Receptor Interferes with HNF-4 Signaling by Targeting a Common Coactivator PGC-1α FUNCTIONAL IMPLICATIONS IN HEPATIC CHOLESTEROL AND GLUCOSE METABOLISM
TL;DR: In this article, the authors examined the functional cross-talk between human PXR and HNF-4, a key hepatic activator of genes involved in bile acid biosynthesis.
Journal ArticleDOI
Mechanism of rifampicin and pregnane X receptor inhibition of human cholesterol 7α-hydroxylase gene transcription
Tiangang Li,John Y.L. Chiang +1 more
TL;DR: The results suggest that activation of PXR by rifampicin promotes P XR interaction with HNF4 alpha and blocks PGC-1 alpha activation with H NF4alpha and results in inhibition of CYP7A1 gene transcription, a protective mechanism against drug and bile acid-induced cholestasis.
Journal ArticleDOI
Mechanisms of cholestasis.
Gernot Zollner,Michael Trauner +1 more
TL;DR: An overview of the molecular and cellular mechanisms of cholestasis is given in this paper, where the authors discuss the pathomechanisms of hereditary CHs, hepatocellular transporter defects, and adaptive hepato-cellular mechanisms counteracting CH liver damage.
Journal ArticleDOI
Ursodeoxycholic acid and bile-acid mimetics as therapeutic agents for cholestatic liver diseases: An overview of their mechanisms of action
TL;DR: The biological properties of UDCA, NorUDCA and FXR agonists are highlighted, as well as their overlapping mechanisms of action in inflammatory biliary disorders.
Journal ArticleDOI
Glycine and taurine conjugation of bile acids by a single enzyme. Molecular cloning and expression of human liver bile acid CoA:amino acid N-acyltransferase.
TL;DR: It is demonstrated that a single cDNA is present in human liver which codes for a protein capable of catalyzing the conjugation of cholic acid with both glycine and taurine.