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.
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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 protects the liver from bile acid overload during liver regeneration in mice
Noémie Péan,Noémie Péan,Isabelle Doignon,Isabelle Garcin,Aurore Besnard,Boris Julien,Bingkaï Liu,Sophie Branchereau,Anne Spraul,Catherine Guettier,Lydie Humbert,Kristina Schoonjans,Dominique Rainteau,Thierry Tordjmann +13 more
TL;DR: TGR5 is crucial for liver protection against BA overload after PH, primarily through the control of bile hydrophobicity and cytokine secretion.
Journal ArticleDOI
TGR5 reduces macrophage migration through mTOR-induced C/EBPβ differential translation
Alessia Perino,Thijs W.H. Pols,Mitsunori Nomura,Sokrates Stein,Roberto Pellicciari,Kristina Schoonjans +5 more
TL;DR: Results reveal a signaling pathway downstream of TGR5 that modulates chemokine expression in response to high-fat diet and suggest that targeting this pathway has the potential to be therapeutically exploited for prevention of chronic inflammatory diseases and type 2 diabetes mellitus.
Journal ArticleDOI
Functional importance of ICAM-1 in the mechanism of neutrophil-induced liver injury in bile duct-ligated mice.
TL;DR: Neutrophils relevant for the aggravation of acute cholestatic liver injury in BDL mice accumulate in hepatic sinusoids, extravasate into the tissue dependent on ICAM-1, and cause cell damage involving reactive oxygen formation.
Journal ArticleDOI
Bile Acids Affect Liver Mitochondrial Bioenergetics: Possible Relevance for Cholestasis Therapy
TL;DR: It is demonstrated that at toxicologically relevant concentrations, most but not all bile acids alter mitochondrial bioenergetics, so impairment of mitochondrial function can be clinically relevant for patients with cholestasis.
Journal ArticleDOI
Bile Salt–Induced Apoptosis Involves NADPH Oxidase Isoform Activation
Roland Reinehr,Stephan Becker,Verena Keitel,Andrea Eberle,Susanne Grether–Beck,Dieter Häussinger +5 more
TL;DR: The data suggest that hydrophobic bile salts activate NADPH oxidase isoforms with the resulting oxidative stress response triggering activation of the CD95 system and apoptosis, and were sensitive to inhibition of sphingomyelinase, PKCzeta, or NAD PH oxidases.