Protection by dietary proteins against the effects of bile acids on rat jejunum and stomach.

Because bile acids bind to certain proteins we examined whether the effect of dihydroxy bile acids on jejunal water transport and gastric mucosal function could be blocked by the presence of protein. In the rat jejunum 2.5% bovine serum albumin blocked the secretion of water and electrolytes induced by 2 mM deoxycholate, whereas 5% ovalbumin, which does not bind bile acids, had no effect. Bovine serum albumin protected large unilamellar liposomes from damage by taurodeoxycholate and reduced the monomer concentration of taurodeoxycholate, whereas ovalbumin afforded no protection. In equilibrium dialysis studies whey protein and bovine serum albumin reduced the free taurodeoxycholate concentration (150 mM HCl enhanced this effect). In the rat stomach taurodeoxycholate (2.5 or 10 mM) in the presence of 150 mM HCl reduced potential difference and enhanced sodium secretion and hydrogen ion loss. These effects were reduced in the presence of whey protein. We conclude that proteins that bind bile acids have the potential to protect mucosal membranes from the adverse effects of bile acids.

Effects of sulfodeoxycholate on rat and rabbit small intestine.

To determine how sulfation alters the biological properties of dihydroxy bile acids, we compared the effects of 3-sulfodeoxycholate (SDC) and deoxycholate (DC) in the rat and rabbit intestine. While 5 mM DC induced water and electrolyte secretion and inhibited glucose absorption in the rat, SDC enhanced jejunal and ileal water and solute absorption. SDC had no effect in the rabbit ileum. In the rat jejunum DC caused mucosal injury and enhanced mucosal permeability while SDC had no effect. In vitro in the rabbit ileum, 10 mM SDC enhanced net sodium flux and decreased net residual flux, while 0.5 mM DC reduced net sodium flux and induced Cl- secretion. Both bile acids increased short-circuit current and potential difference and decreased tissue conductance. During reversed-phase, high-performance liquid chromatography SDC was more polar than DC. Sulfation reduced the ability of DC to destroy large unilamellar liposomes by a factor of 10. Thus, sulfation abolishes the effects of DC on the intestine by enhancing the polarity of this molecule. The enhancement of intestinal solute and water absorption by SDC requires further study.

Hepatic free fatty acids in alcoholic liver disease and morbid obesity.

Alcoholic liver disease is characterized by the accumulation of fat and inflammatory changes in the liver. Because free fatty acids, the precursors of triglycerides, can damage biological membranes, accumulation of free fatty acids in the liver might be in part responsible for the functional and morphological changes seen in alcoholic liver disease. We, therefore, determined the hepatic lipid composition in biopsies from 31 patients with alcoholic liver disease, 18 patients with morbid obesity, and 5 patients without evidence of liver disease. Free fatty acids were found in all liver biopsies. Patients with morbid obesity or alcoholic liver disease had significantly higher fatty acid and triglyceride levels than did controls (p less than 0.01). Patients with alcoholic liver disease had significantly higher fatty acid levels than did patients with morbid obesity (p less than 0.05), while there was no difference in the triglyceride concentrations between these two groups. The distribution of the fatty acids in the free fatty acid fraction differed significantly from that in the triglyceride fraction indicating a preferential incorporation of unsaturated fatty acids into triglycerides. This difference in the distribution pattern was lost in patients with the most severe forms of alcoholic liver disease. The data are consistent with the hypothesis that accumulation of free fatty acids in patients with alcoholic liver disease may be responsible for or contribute to the observed functional and morphological damages.