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The role of bile acids in pharmacotherapy is reviewed in this article. The therapeutic use of bile has been recognized since ancient times. Previously bile acids were the standard treatment for gallstones where chenodeoxycholic acid and ursodeoxycholic acid were effective in promoting the dissolution of cholesterol gallstones. Today their therapeutic role looks set to expand enormously. Bile acids as absorption promoters have the potential to aid intestinal, buccal, transdermal, ocular, nasal, rectal and pulmonary absorption of various drugs at concentrations that are non-toxic. Keto derivatives of cholic acid, such as 3a,7a,dihydroxy-12-keto-5alpha-cholic acid (sodium salt and methyl ester) are potential modifiers of blood-brain barrier transport and have been shown to promote quinine uptake, enhance the analgesic effect of morphine and prolong the sleeping time induced by pentobarbital. They have also been shown to be hypoglycaemic. Bile acids as therapeutic agents have the potential to produce beneficial effects in sexually transmitted diseases, primary biliary cirrhosis, primary sclerosing cholangitis, gallstones, digestive tract diseases, cystic fibrosis, cancer and diabetes.

A comparative study was carried out on the effect of molybdenum (Mo), nickel (Ni), cadmium (Cd), and lead (Pb) using concentrations of 1610 À 7 , 1610 À 5 , and 1610 À 3 mol dm À 3 , on the metabolism of nitrogen and proteins in young pea plants (Pisum sativum L.`NS Lim'). The highest concentrations of the investigated metals were noted to suppress the development of the aboveground parts and roots. The smallest inhibiting effect was observed in the presence of Ni, which at lowest concentration produced a stimulating effect; Pb and Cd had a similar effect. The most pronounced inhibition was caused by Mo, which decreased the growth of the roots and aboveground parts by 50% and 35%, respectively. An increase in concentration of heavy metals in the medium resulted in their increased JOURNAL accumulation in both the plant roots and aboveground parts. The largest accumulation in the aboveground parts was observed for Ni and Mo, followed by Cd, and least for Pb. Nitrate and protein metabolism decreased according to the order of Cd b Pb b Ni b Mo. However, when expressed per amount of heavy metal accumulated in particular plant parts, toxicity was in the order of Pb b Cd b Ni b Mo.

An overview of the structure and the origin of naturally occurring bile acids is given. Most naturally occurring bile acids belong to the 5beta-series, with hydroxyl groups in the A, B, and C ring of the steroid system. Hydroxyl groups are mostly found at the C3, C6, C7, C12 and C23 positions and are a- rather than beta-oriented. In most bile acids, the A/B ring junction is cis (5beta-series). However, the A ring can be usually present in the more stable (chair) or less stable (boat) conformation. Both B/C and C/D ring junction are trans. With respect to the angular C19-methyl group, the hydrogen atoms at C5 and C8 are cis-oriented whereas those at C9 and C14 are trans-oriented. The archetypal bile acid is 5beta-cholanic acid (3) from which all other C24 bile acids can be derived. In addition to the bile acids with 24 carbons, some naturally occurring C27 bile acids have been identified including di-, tri- and tetra-hydroxy derivatives of coprostanic acid isolated from bile of several reptile species. The most dominant bile acids and their natural sources are given and a selection of naturally occurring bile acids with unusual structures which have been mostly isolated from the bile of reptiles and amphibians is described.