China
Africa
Explore chapters and articles related to this topic
Ursodeoxycholic Acid Treatment of Vanishing Bile Duct Syndromes
Published in Gianfranco Alpini, Domenico Alvaro, Marco Marzioni, Gene LeSage, Nicholas LaRusso, The Pathophysiology of Biliary Epithelia, 2020
The nature of hepatocyte cell death in cholestatic liver disease remains poorly understood. However, since widespread necrosis is usually not observed in cholestatic liver disease, it was proposed that hepatocyte cell death during cholestasis occurs by apoptosis.46 Indeed, apoptotic features have been observed more frequendy in liver tissue from patients with PBC than in normal controls.47 Toxic bile acids can induce apoptosis in hepatocytes at concentrations that are found in chronic cholestasis. The mechanisms of bile acid-induced apoptosis have been partially elucidated in recent years. Glycochenodeoxycholic acid (GCDCA), a pro-apoptotic bile acid, directly causes apoptosis in vitro in hepatocytes by ligand-independent activation of Fas48 and probably TRAIL receptor2/DR5.49 Subsequendy, a death inducing signaling complex (DISC) is formed and leads to activation of caspase-8, followed by activation of Bid, a pro-apoptotic member of the Bcl-2 protein family.50 Activated Bid chaperons Bax, another pro-apototic Bcl-2 molecule, to the mitochondrial membrane.51 Bid and Bax and presumably additional so far unidentified factors cause the mitochondrial membrane permeability transition (MMPT), a phenomenon characterized by a sudden permeability increase of the inner mitochondrial membrane to ions, followed by mitochondrial swelling.52 Mitochondrial swelling is thought to induce the release of cytochrome c from the intermembrane space to the cytosol, where it activates caspase-9 through interaction with the apoptotic protease-activating factor 1 (APAF-1).53 The apoptotic demise of the cell is then mediated by effector caspases (-3, -6 and -7), which are activated by caspase-9.
The double-edged sword of probiotic supplementation on gut microbiota structure in Helicobacter pylori management
Published in Gut Microbes, 2022
Ali Nabavi-Rad, Amir Sadeghi, Hamid Asadzadeh Aghdaei, Abbas Yadegar, Sinéad Marian Smith, Mohammad Reza Zali
Hepatocytes synthesize primary bile acids from cholesterol, conjugate them to taurine or glycine, and then release them into the gall bladder to form bile in combination with cholesterol, phospholipids, minerals, electrolytes, bilirubin, biliverdin, and protein.46 Intestinal bacteria will deconjugate primary BAs that fail reabsorption in the terminal ileum and thereby convert them to secondary BAs by microbial biotransformation, including dehydroxylation, epimerization, and oxidation of hydroxyl groups.47 Secondary BAs are involved in the modulation of cell signaling, microbial composition, intestinal metabolism, and the host immune response. Reduced BA deconjugation is associated with inflammatory bowel diseases (IBD) including ulcerative colitis (UC) and Crohn’s disease (CD), as well as irritable bowel syndrome (IBS).48 Free BAs, such as cholic acid, deoxycholic acid, and chenodeoxycholic acid, can stimulate apoptosis and reduce interleukin 6 (IL-6) production, while conjugated BAs such as glycolic acid, glycodeoxycholic acid, and glycochenodeoxycholic acid promote cell growth and induce IL-6 production.49 However, excessive production of the secondary BA deoxycholic acid triggers the expression of inflammatory and tumorigenic factors in hepatic stellate cells (HSCs), contributing to hepatocellular carcinoma development.50 Secondary BAs might also activate farnesoid X receptor (FXR) and elevate the risk of developing colorectal cancer and hepatocellular carcinoma.51
Pharmacological effects of nanoencapsulation of human-based dosing of probucol on ratio of secondary to primary bile acids in gut, during induction and progression of type 1 diabetes
Published in Artificial Cells, Nanomedicine, and Biotechnology, 2018
Armin Mooranian, Nassim Zamani, Ryu Takechi, Hesham Al-Sallami, Momir Mikov, Svetlana Goločorbin-Kon, Bozica Kovacevic, Frank Arfuso, Hani Al-Salami
Diabetes mellitus has two main types, Type 1 Diabetes (T1D) and Type 2 Diabetes (T2D) and they share common symptoms such as hyperglycaemia and low-grade inflammation [1,2]. Several published studies have associated diabetes development and inflammation with changes in the bile acid profile, in terms of concentrations of primary and secondary bile acids in plasma and tissues [3]. Kirkpatrick RB and Kraft BG have shown that T1D induction causes significant inflammation and alteration in liver-associated enzymatic activities and results in substantial activation of hepatic bile acid sulfotransferase enzymes, and a marked increase in bile acid flow, bile acid excretion and levels of secondary bile acids in gut [4]. Thomson has shown that development of diabetes exerts direct and significant effects on bile acids uptake from various parts of the intestinal tract including jejunum, ileum and colon. The author showed that changes within the absorbing layers of the body may have direct effects on how much bile acids are absorbed and rates and extent of absorption of different types of primary and secondary bile acids. The intestinal uptake of cholic acid, glycocholic acid, taurocholic acid, chenodeoxycholic acid, glycochenodeoxycholic acid and deoxycholic acid were measured in healthy and T1D rats. T1D rats showed significant variation in maximal bile acid transport, compared with healthy rats, which illustrates specific effects of T1D development on the relative permeability of different segments of the gastrointestinal tract to bile acid uptake [5].
Evaluation of liver function by means of serum cytokeratin 18 and hepatocyte growth factor levels in patients with obstructive jaundice
Published in Acta Chirurgica Belgica, 2018
Nurinnisa Ozturk, Gurkan Ozturk, Serkan Cerrah, Sabri Selcuk Atamanalp, Mehmet Ali Gul, Nurhak Aksungur, Nuri Bakan, Ebubekir Bakan
When untreated, cholestasis can result in hepatotoxicity, inflammation and cirrhosis and this pathological situation is a common component of numerous liver diseases. Cholestasis caused by obstructive jaundice makes the treatment of jaundice associated hepato-biliary diseases more complicated. Severe hepatocyte damage due to obstruction-associated cholestasis alters inflammation at the liver and thereby postoperative morbidity and mortality [16]. Obstructive jaundice is a common cause of persistent cholestasis. Persistent cholestasis gives rise to injury in hepatocytes and in bile duct epithelial cells and inflammation [16]. It is assumed that the mechanism of cholestatic liver injury is the accumulation of hydrophobic bile salts and their bile acid forms. Glycochenodeoxycholate (GCDC) and its bile acid glycochenodeoxycholic acid (GCDCA) are the most aforementioned agents. Whether these toxic accumulations cause cell death with apoptosis is a debate [16].