The Effects of Boron Derivatives on Lipid Absorption from the Intestine and on Bile Lipids and Bile Acids of Sprague Dawley Rats

摘要

N,N-dimethyl-n-octadecylamine borane 1 at 8 mg/kg/day, tetrakis-u-(trimethylamineboranecarboxylato)-bis(trimethyl-carboxyborane)-dicopper(II) 2 at 2.5 mg/kg/day and trimethylamine-carboxyborane 3 at 8 mg/kg/day were evaluated for their effects on bile lipids, bile acids, small intestinal absorption of cholesterol and cholic acid and liver and small intestinal enzyme activities involved in lipid metabolism. The agent administered orally elevated rat bile excretion of lipids, e.g. cholesterol and phospholipids, and compounds 2 and 3 increased the bileflow rate. These agents altered the composition of the bile acids, but there was no significantincrease in lithocholic acid which is most lithogenic agent in rats. The three agents did decreasecholesterol absorption from isolated in situ intestinal duodenum loops in the presence of drug.Hepatic and small intestinal mucosa enzyme activities, e.g. ATP-dependent citrate lyase, acylCoA cholesterol acyl transferase, cholsterol-7-α -hydroxylase, sn glycerol-3-phosphate acyltransferase, phosphatidylate phosphohydrolase, and lipoprotein lipase, were reduced. However,the boron derivatives 1 and 3 decreased hepatic HMG-CoA reductase activity, the regulatoryenzyme for cholesterol synthesis, but the compounds had no effects on small intestinal mucosaHMG-CoA reductase activity. There was no evidence of hepatic cell damage afforded by thedrugs based on clinical chemistry values which would induce alterations in bile acid concentrationsafter treatment of the rat.