title: Recent understanding of cholesterol gallstone pathogenesis: implication to non-surgical therapeutic strategy.
abstract: This article reviews the recent understanding of cholesterol gallstone pathogenesis in light of etiology and molecular mechanisms of the cholesterol gallstone formation process, to provide the future direction of a non-surgical therapeutic strategy. In principle, cholesterol gallstone formation, which is associated with an altered bile salt metabolism, is based primarily upon the impairment of cholesterol metabolism and homeostasis. Cholesterol is eliminated physiologically into bile; thus, the excess cholesterol induces bile metastability due to a relative insufficiency of bile salt, to initiate cholesterol crystal nucleation in the gallbladder with an impaired function. Those crystals grow to become macroscopic stones in the gallbladder mucin gel, accumulated under an arachidonate-prostanoid pathway induced-hypersecretion by the gallbladder wall. These events can be modified by bile salt supplementation, which provides a detergent action. Therefore, oral bile salt administration is a cost-effective, non-surgical therapy under certain circumstances. Understanding the pathogenesis of cholesterol gallstones attributes to the therapeutic guideline based upon scientific and clinical evidence.
authors.affiliation: Department of General Medicine, Hiroshima University Hospital, Hiroshima, Japan. stazuma@hiroshima-u.ac.jp.|Department of Clinical Pharmacotherapy, Programs of Applied Medicine, Graduate School of Medical Science, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan. stazuma@hiroshima-u.ac.jp.
authors.forename: Susumu
authors.initials: S
authors.lastname: Tazuma
keywords: ATP-dependent binding cassette transporters; Bile salt; Cholesterol; Gallstones; Nuclear receptors; Phospholipids