Lithocholic acid and derivatives: Antibacterial activity.

In order to develop bioactive lithocholic acid derivatives, we prepared fifteen semi-synthetic compounds through modification at C-3 and/or C-24. The reactions showed yields ranging from 37% to 100%. The structures of all compounds obtained were identified on the basis of their spectral data (IR, MS, 1D- and 2D-NMR). The activity of lithocholic acid and derivatives was evaluated against the growth of Escherichia coli, Staphylococcus aureus, Bacillus cereus and Pseudomonas aeruginosa. The derivative 3α-formyloxy-5ß-cholan-24-oic acid (LA-06) showed the best activity, with MIC values of 0.0790 mM against E. coli (Ec 27) and B. cereus in both cases, and 0.0395 mM against S. aureus (ATCC 12692). Lithocholic acid and the derivatives with MIC⩽1.2 mM were evaluated on the susceptibility of some bacterial pathogens to the aminoglycoside antibiotics neomycin, amikacin and gentamicin was evaluated. There are no previously reported studies about these compounds as modifiers of the action of antibiotics or any other drugs.

Morphologic changes in livers of hamsters treated with high doses of ursodeoxycholic acid: correlation with bile acids in bile.

The effects of high doses of ursodeoxycholic acid on bile acid composition and the liver morphology was examined in 60 male Syrian golden hamsters. The animals were allocated to five groups: I, control; II and IV received 0.5 g and 1 g of ursodeoxycholic acid per 100 g of standard diet respectively over 30 days and III and V received 0.5 g and 1 g of ursodeoxycholic acid per 100 g of standard diet respectively over 60 days. Bile acids were determined by high performance liquid chromatography. In all treated groups there was a significant increase in chenodeoxycholic and lithocholic acid in the bile. The mean glyco/tauro ratio was significantly higher than in the control group, reaching values > 1 for individual bile acids, except for lithocholic acid values which remained < 1. Under light microscopy, the livers of the hamsters showed damage which was dose/time related, namely portal inflammatory infiltrate, bile duct proliferation, cholestasis, fat infiltration and necrosis. Electron microscopy revealed pronounced changes starting with microvilli edema and extending to canalicular membrane destruction and necrosis. The changes observed in the relation glyco/tauro lithocholic acids, may be due to defence mechanisms to avoid hepatotoxicity. The hepatotoxicity resulting from ursodeoxycholic acid administration is presumed to be due primarily to lithocholic acid or some lithocholic acid metabolite.

[Determination of cholic and sulfolithocholic acids in various hepatopathies]. / Determinación de los ácidos cólico y sulfolitoglicocólico en diferentes hepatopatías.

The conjugated cholic acid (glycocholic acid) (GC) in the serum and the conjugated sulfolithocholic acid (sulfolithoglycocholic acid (SLGC) in 35 aggressive chronic hepatitis (HCA), 22 cirrhosis, 11 primary biliary cirrhosis (CBP), 11 pruritus of pregnancy and in 20 normal controls were determined. The control group revealed a mean value of GC of 21 micrograms % with a dispersion of +/- 14 micrograms % and for SLGC of 36 micrograms % with a dispersion of +/- 9 micrograms %. The frequency of the alteration of GC and SLGC in the cases of chronic hepatitis was low (14% and 9%) as well as in the cirrhosis (23% and 14%). In the pruritus of pregnancy the values reached 64% and 45%. On the other hand, the values were significantly elevated in CBP (100% and 90%) (p.001 and p.006). The absolute values in the various pathologies revealed mean values which were different but with a very wide dispersion that prevented us from seeing any relation between those absolute values and the different diseases. The alteration in the metabolism of biliary acids in the hepatic pathology was manifested by the postprandial determination of GC and SLGC in 20 HCA in whom the frequency of abnormal values rose from 14% and 9% on fasting to 60% and 45% prandially.