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Titolo:
Arachidyl amido cholanoic acid (Aramchol) is a cholesterol solubilizer andprevents the formation of cholesterol gallstones in inbred mice
Autore:
Gilat, T; Leikin-Frenkel, A; Goldiner, I; Laufer, H; Halpern, Z; Konikoff, FM;
Indirizzi:
Tel Aviv Univ, Sourasky Tel Aviv Med Ctr, Dept Gastroenterol, IL-69978 TelAviv, Israel Tel Aviv Univ Tel Aviv Israel IL-69978 enterol, IL-69978 TelAviv, Israel Tel Aviv Univ, Sackler Fac Med, Minerva Ctr Cholesterol Gallstones & LipidMetab, IL-69978 Tel Aviv, Israel Tel Aviv Univ Tel Aviv Israel IL-69978 dMetab, IL-69978 Tel Aviv, Israel
Titolo Testata:
LIPIDS
fascicolo: 10, volume: 36, anno: 2001,
pagine: 1135 - 1140
SICI:
0024-4201(200110)36:10<1135:AACA(I>2.0.ZU;2-7
Fonte:
ISI
Lingua:
ENG
Soggetto:
BILE-ACIDS; STONE RECURRENCE; MODEL BILES; DISSOLUTION; CRYSTALLIZATION; PHOSPHOLIPIDS; NUCLEATION; THERAPY; TIME;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Agriculture,Biology & Environmental Sciences
Life Sciences
Citazioni:
22
Recensione:
Indirizzi per estratti:
Indirizzo: Gilat, T 10 Nehardea St, IL-64235 Tel Aviv, Israel 10 Nehardea St Tel Aviv Israel IL-64235 -64235 Tel Aviv, Israel
Citazione:
T. Gilat et al., "Arachidyl amido cholanoic acid (Aramchol) is a cholesterol solubilizer andprevents the formation of cholesterol gallstones in inbred mice", LIPIDS, 36(10), 2001, pp. 1135-1140

Abstract

We have recently synthesized fatty acid bile acid conjugates (FABAC) that were able to reduce and retard cholesterol crystallization in model and human biles. When given orally, they prevented the formation of cholesterol crystals in the bile of hamsters. The aim of the present study was to determine whether the FABAC are cholesterol solubilizers, whether they can dissolve pre-existing crystals, whether they can prevent the formation of cholesterol gallstones, and to investigate the optimal type of bond between the fatty acid and bile acid. The presence of cholesterol crystals was determined by light microscopy, and the total crystal mass of precipitated crystals was measured by chemical means. Inbred (C57J/L) mice on a lithogenic diet were used to evaluate cholesterol crystal formation, dissolution, and gallstone formation in vivo. Arachidyl amido cholanoic acid (Aramchol) was the FABAC used in the present experiments. At equimolar amounts, the cholesterol-solubilizing capacity of Aramchol was higher than that of taurocholate and similar to that of phosphatidylcholine. The addition of Aramchol dissolved approximately 50% of preexisting crystals in model bile solutions. The same phenomenon was demonstrated in human bile ex vivo, with a dose-response effect. All inbred mice developed cholesterol crystals in bile after 10-14 d onthe lithogenic diet. Thereafter, supplementation of the diet with Aramcholprogressively reduced the proportion of mice with crystals to 25% after 28d. On the lithogenic diet, 100% of inbred mice developed cholesterol gallstones in the gallbladder by day 21. None of the mice whose diet was supplemented with 0.5 mg or 1.0 mg of Aramchol/d developed stones or crystals. FABAC are a new class of molecules that are cholesterol solubilizers and whichare able to dissolve cholesterol crystals in bile. Upon oral administration, they dissolve pre-existing cholesterol crystals and prevent the formation of gallstones in gallstone-susceptible mice.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 04/04/20 alle ore 08:47:05