Prevention of cholesterol gallstones by inhibiting hepatic biosynthesis and intestinal absorption of cholesterol

Abstract

Cholesterol cholelithiasis is a multifactorial disease influenced by a complex interaction of genetic and environmental factors, and represents a failure of biliary cholesterol homeostasis in which the physical-chemical balance of cholesterol solubility in bile is disturbed. The primary pathophysiologic event is persistent hepatic hypersecretion of biliary cholesterol, which has both hepatic and small intestinal components. The majority of the environmental factors are probably related to Western-type dietary habits, including excess cholesterol consumption. Laparoscopic cholecystectomy, one of the most commonly performed surgical procedures in the US, is nowadays a major treatment for gallstones. However, it is invasive and can cause surgical complications, and not all patients with symptomatic gallstones are candidates for surgery. The hydrophilic bile acid, ursodeoxycholic acid (UDCA) has been employed as first-line pharmacological therapy in a subgroup of symptomatic patients with small, radiolucent cholesterol gallstones. Long-term administration of UDCA can promote the dissolution of cholesterol gallstones. However, the optimal use of UDCA is not always achieved in clinical practice because of failure to titrate the dose adequately. Therefore, the development of novel, effective, and noninvasive therapies is crucial for reducing the costs of health care associated with gallstones. In this review, we summarize recent progress in investigating the inhibitory effects of ezetimibe and statins on intestinal absorption and hepatic biosynthesis of cholesterol, respectively, for the treatment of gallstones, as well as in elucidating their molecular mechanisms by which combination therapy could prevent this very common liver disease worldwide.

Novel bile acid sequestrant: A biodegradable hydrogel based on amphiphilic allylamine copolymer

“…The organism response leads to cholesterol consumption, which reduces the serum cholesterol levels. 6,[16][17][18] Polymeric BAS materials, are normally prepared from amine-containing polymer precursors, such as polyethylenimine, quaternized polystyrene, poly(vinylamine), and poly(allylamine) hydrochloride (PAH). 19 Because of the high chemical reactivity and excellent biocompatibility, PAH and its derivatives are used in many biological and medical fields, including drug-release, 20 gene therapy, 21 biomedical microencapsulation 22 , and heparin reversal.…”

The Effect of Bioactive Component of Turmeric (curcumin) on Liver Complications - Induced by Compact Fluorescent Lamps (CFLs) in Rats

“…This damage of liver can be due to UV radiation (11). Although hypercholesterolemia is produced in our experiment with liver damage, in order that the synthesis of cholesterol occurs in many cells for example intestine, adrenal cortex and reproductive tissues (29). Recently, studies showed that high intensity and prolonged fluorescent exposure lights are harmful to all living organisms and produce hemolysis of erythrocyte, this results in an increase in plasma bilirubin (30,31).…”

Preventing a Mass Disease: The Case of Gallstones Disease. Role and Competence for Family Physicians

“…The studies published so far were mainly experimental or incomplete, with a lack of clinical relevance. The investigated agents include the bile acid ursodeoxycholic acid (UDCA), omega-3 fatty acids, 48) statins, 18) ezetimibe, 18,49,50) aspirin, 51) and liver nuclear receptor regulators of cholesterol metabolism, i.e., FXR (farnesoid X receptor) agonists.…”