Sulphated Lithocholic Acid Conjugates in Serum from Children with Hepatic and Intestinal Diseases

Kuipers, Folkert; Bijleveld, Cma; Kneepkens, C. M. F.; Zanten, van; Fernandes, J.; Vonk, Roelf

doi:10.3109/00365528509089286

Cited by 13 publications

(10 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These data highlight the role of TLC‐S not only as the most potent Ca 2+ releaser among bile acids tested on PACs so far, but also as the most effective bile acid in inducing Ca 2+ ‐independent current, even at 10 µ m . This concentration is close to the concentrations of sulphated lithocholic acid conjugates detected in serum in different pathological conditions 17 . Indeed, in patients with severe extrahepatic duct obstruction, concentrations of bile acids of ∼200 µ m have been detected in peripheral circulation 18 …”

Section: Bile Acids and Their Targetssupporting

confidence: 75%

Review of experimental animal models of biliary acute pancreatitis and recent advances in basic research

Wan

Huang

Latawiec

et al. 2012

HPB

View full text Add to dashboard Cite

Acute pancreatitis (AP) is a formidable disease, which, in severe forms, causes significant mortality. Biliary AP, or gallstone obstruction-associated AP, accounts for 30-50% of all clinical cases of AP. In biliary AP, pancreatic acinar cell (PAC) death (the initiating event in the disease) is believed to occur as acinar cells make contact with bile salts when bile refluxes into the pancreatic duct. Recent advances have unveiled an important receptor responsible for the major function of bile acids on acinar cells, namely, the cell surface G-protein-coupled bile acid receptor-1 (Gpbar1), located in the apical pole of the PAC. High concentrations of bile acids induce cytosolic Ca(2+) overload and inhibit mitochondrial adenosine triphosphate (ATP) production, resulting in cell injury to both PACs and pancreatic ductal epithelial cells. Various bile salts are employed to induce experimental AP, most commonly sodium taurocholate. Recent characterization of taurolithocholic acid 3-sulphate on PACs has led researchers to focus on this bile salt because of its potency in causing acinar cell injury at relatively low, sub-detergent concentrations, which strongly implicates action via the receptor Gpbar1. Improved surgical techniques have enabled the infusion of bile salts into the pancreatic duct to induce experimental biliary AP in mice, which allows the use of these transgenic animals as powerful tools. This review summarizes recent findings using transgenic mice in experimental biliary AP.

show abstract

Section: Bile Acids and Their Targetssupporting

confidence: 75%

Review of experimental animal models of biliary acute pancreatitis and recent advances in basic research

Wan

Huang

Latawiec

et al. 2012

HPB

View full text Add to dashboard Cite

show abstract

“…Therefore, even minor reflux of this toxic bile component into the pancreas will most probably have deleterious effects on pancreatic functions. The low level of TLC-S, which has been found in this study to activate the Ca 2ϩ -independent current, is close to the concentrations of sulfated lithocholic acid conjugates detected in serum in different pathological conditions (33,34). The concentration of TLC-S necessary to induce cationic current is even smaller than that required to trigger cytosolic calcium responses (in our previous work we found that a higher concentration of TLC-S (25 M) produced calcium responses in only 11% of the cells tested) and similar to the threshold concentration that has been reported to induce transient mitochondrial depolarization (35).…”

Section: Bile Induces Cationic Current and Intracellular Nasupporting

confidence: 83%

Bile Acids Induce a Cationic Current, Depolarizing Pancreatic Acinar Cells and Increasing the Intracellular Na+ Concentration

Voronina¹,

Gryshchenko²,

Gerasimenko

et al. 2005

Journal of Biological Chemistry

View full text Add to dashboard Cite

Biliary disease is a major cause of acute pancreatitis. In this study we investigated the electrophysiological effects of bile acids on pancreatic acinar cells. In perforated patch clamp experiments we found that taurolithocholic acid 3-sulfate depolarized pancreatic acinar cells. At low bile acid concentrations this occurred without rise in the cytosolic calcium concentration. Measurements of the intracellular Na ؉ concentration with the fluorescent probe Sodium Green revealed a substantial increase upon application of the bile acid. We found that bile acids induce Ca 2؉ -dependent and Ca 2؉ -independent components of the Na ؉ concentration increase. The Ca 2؉ -independent component was resolved in conditions when the cytosolic Ca 2؉ level was buffered with a high concentration of the calcium chelator 1,2-bis(oaminophenoxy)ethane-N,N,N,N-tetraacetic acid (BAPTA). The Ca 2؉ -dependent component of intracellular Na ؉ increase was clearly seen during stimulation with the calcium-releasing agonist acetylcholine. During acetylcholine-induced Ca 2؉ oscillations the recovery of cytosolic Na ؉ was much slower than the recovery of Ca 2؉ , creating a possibility for the summation of Na ؉ transients. The bile-induced Ca 2؉ -independent current was found to be carried primarily by Na ؉ and K ؉ , with only small Ca 2؉ and Cl ؊ contributions. Measurable activation of such a cationic current could be produced by a very low concentration of taurolithocholic acid 3-sulfate (10 M). This bile acid induced a cationic current even when applied in sodium-and bicarbonate-free solution. Other bile acids, taurochenodeoxycholic acid, taurocholic acid, and bile itself also induced cationic currents. Bile-induced depolarization of acinar cells should have a profound effect on acinar fluid secretion and, consequently, on transport of secreted zymogens.

show abstract

“…Serum SGLC, glycine cholate and 3tuOH-bile acids were determined as part of a study on the prevalence of elevated serum SGLC in pediatric patients with intestinal and hepatic disorders (10). In contrast to healthy controls, mean serum SGLC during cholestasis-free intervals was increased 2.8 f. 0 3 (S.E.)…”

Section: Resultsmentioning

confidence: 99%

“…Furthermore, sulfated monohydroxy bile acids are also cholestatic in the rat (35)(36)(37). Since lithocholic acid and its sulfated form are also components of human bile, we studied their presence in serum of children and their metabolism in rats (10). The cholestatic effect of SGLC was more pronounced when the endogenous bile acid pool was contracted (36).…”

Section: Discussionmentioning

confidence: 99%

“…a distinct rise in serum SGLC was observed in both patients ( Fig. 3), in contrast to healthy controls (10). Figure 3 also shows that this postprandial rise in serum SGLC did not occur when cholestyramine was added to the testmeal, or when medium-chain triglycerides were substituted for longchain triglycerides.…”

Section: Bile Acid Metabolism Besides Familial Factorsmentioning

confidence: 99%

See 1 more Smart Citation

Benign recurrent intrahepatic cholestasis: A long-term follow-up study of two patients

et al. 1989

View full text Add to dashboard Cite

Two brothers with benign recurrent intrahepatic cholestasis were studied over a period of 6 years. During this period, 11 episodes of cholestasis were observed, with a mean duration of 2.6 months (range: 2 weeks to 6 months). Once, both brothers developed cholestasis simultaneously. There was a prevalence for episodes of cholestasis in wintertime. The postprandial rise in serum sulfated glycolithocholic acid was increased in the patients, and the bile acid pool was enriched with secondary bile acids. In periods prior to cholestasis, the urinary 3 alpha OH-bile acid concentration was often elevated (greater than 50 mumoles per liter) without a clear correlation with the clinical prodromata. However, it could not be used as a predictor of cholestasis. In contrast, the postprandial rise in serum 3 alpha OH-bile acids was always grossly elevated in periods just before cholestasis. An increase both in fecal bile acid excretion as well as secondary bile acids in the bile acid pool indicated an increased spillover of bile acids into the large bowel. Cholestyramine administered directly after the first signs of cholestasis appeared to shorten an episode of cholestasis. On the other hand, withdrawal of cholestyramine in a cholestasis-free period may have resulted in an episode of cholestasis. Neither taurine supplementation for 3 and 7 weeks nor calcium phosphate, which binds sulfated bile acids in vitro, for 3 weeks could prevent an episode of cholestasis, although the latter normalized the bile acid pool composition. There is a rationale for a fat-restricted diet and cholestyramine therapy only as maintenance treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

show abstract

Sulphated Lithocholic Acid Conjugates in Serum from Children with Hepatic and Intestinal Diseases

Cited by 13 publications

References 17 publications

Review of experimental animal models of biliary acute pancreatitis and recent advances in basic research

Review of experimental animal models of biliary acute pancreatitis and recent advances in basic research

Bile Acids Induce a Cationic Current, Depolarizing Pancreatic Acinar Cells and Increasing the Intracellular Na+ Concentration

Benign recurrent intrahepatic cholestasis: A long-term follow-up study of two patients

Contact Info

Product

Resources

About