Prevention of cholesterol crystallization in bile using phospholipid derivatives and fatty acid bile acid conjugates

Konikoff, F.M.; Goldiner, Ilana; Sömjen, Giora J.; Laufer, H.; Halpern, Zamir; Gilat, T

doi:10.1016/s0168-8278(00)81122-8

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“…It was then investigated whether parts of the phospholipid molecule such as fatty acids and also mono-or diglycerides could act as cholesterol solubilizers. These studies revealed that saturated long chain fatty acids and some other parts of the phospholipid molecule had cholesterol solubilizing activity [10]. But again, there was no practical way to enrich bile with these compounds.…”

Section: Introductionmentioning

confidence: 99%

Effects of Fatty Acid Bile Acid Conjugates (FABACs) on Biliary Lithogenesis: Potential Consequences for Non-Surgical Treatment of Gallstones

Konikoff

Gilat²

2005

curr drug targets immune endocr metabol disord

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Fatty acid bile acid conjugates (FABACs) are novel synthetic lipid molecules, which were designed for the treatment of cholesterol gallstones. The rationale was to combine a cholesterol solubilizing moiety (a saturated fatty acid) with a bile acid (cholic acid) as a vehicle to enable secretion into bile and entry into the enterohepatic circulation. An amide bond was used to provide stability against intestinal degradation. Initial in vitro studies showed that FABACs are indeed cholesterol solubilizers, able to prevent biliary cholesterol crystallization. Arachidyl-amido-cholanoic acid (Aramchol) was found to be the most potent FABAC in these studies.Animal studies revealed that Aramchol was absorbed after oral administration and could prevent cholesterol crystallization as well as dissolve preformed crystals in rodents fed a lithogenic diet. In gallstone susceptible mice, Aramchol prevented gallstone formation and dissolved gallstones. FABACs were found to be metabolically active substances, also able to decrease blood cholesterol, atherosclerotic plaques and fat accumulation in the liver in several animal species.The underlying mechanisms of action are under active investigation, and several effects, e.g. on cholesterol and bile salt metabolizing enzymes as well as cholesterol efflux from cells have been discovered. These findings are, however, only the beginning of our understanding of the metabolic actions as well as the potential of use of FABACs as therapeutic agents.

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Section: Introductionmentioning

confidence: 99%