Gallbladder motility and gut hormone plasma levels in subjects with and without gallstones.

Hormonal control of gallbladder motility is still unclear in patients with cholelithiasis. In a case-control study, we determined the characteristics of gallbladder emptying evaluated sonographically and the hormone levels of somatostatin, gastrin, and pancreatic polypeptide, before and after a fatty meal in 10 gallstone patients compared with 20 healthy subjects. Patients with lithiasis had a larger residual volume (median 12,0 ml vs 6,5 ml; P = 0.01) and a lower gallbladder ejection fraction (43% vs 70%, P = 0.02) than healthy subjects. During fasting, plasma pancreatic polypeptide concentrations were significantly higher in lithiasis patients (P < 0.03). In contrast, no differences between the two groups of patients were observed during the post prandial period. Somatostatin and gastrin plasma levels were similar in the two groups. Lastly, the serum bile salt levels were in the normal range and were not different between groups both during fasting and postprandial states. We conclude that large basal plasma concentrations of pancreatic polypeptide, a gut peptide inducing gallbladder relaxation, may constitute a factor facilitating lithogenesis.

Conjugation with taurine prevents side-chain desaturation of ursodeoxycholic and beta-muricholic acids in bile fistula rats.

The metabolism of intravenously infused bile salts, tauroursodeoxycholate, tauro-beta-muricholate and their corresponding unconjugated forms in the liver was investigated in bile salt-depleted bile fistula rats. The biliary bile salt composition was determined by gas chromatography-mass spectrometry using chemical positive ionization and electron-impact methods. For an infusion rate of 2 micromol/min/kg, all bile salts were efficiently secreted in bile, inducing similar choleresis. Only tauroconjugated bile salts were recovered; no glucuronide or glyco derivatives were detected. The infusion of free ursodeoxycholate led to the appearance of a metabolite identified as a Delta22 derivative (12%). A similar biotransformation rate (11%) was observed following free beta-muricholate infusion. In contrast, no metabolite was observed after infusion of the tauroconjugated form of ursodeoxycholate and beta-muricholate. The unsaturation process probably depends on the availability of the carboxyl group for the starting step of the beta-oxidation mechanism. In conclusion, the current in vivo study demonstrates a hepatic origin for Delta22 bile salts. It also shows that free bile salts were sensitive to Delta22 formation while conjugation with taurine totally prevented the side-chain oxidation of the two 7beta-hydroxylated bile salts.

Experimental schistosomiasis, protective aspects of granulomatous reaction in the mouse liver.

We show two mechanisms of liver protection by the granulomatous reaction against Schistosoma mansoni eggs entrapped in the organ. First, eosinophil peroxidase and its substrate H(2)O(2) are released by inflammatory cells in the immediate vicinity of the parasite eggs. The efficiency of this process was demonstrated by administration of antioxidants to infected mice. The treatment, which reduces H(2)O(2) production, significantly improved the ability of parasite eggs to hatch after collection from the liver. Secondly, we labeled the released egg antigens in liver histological sections and we found that the lattice of collagen fibers which is built around eggs appears to create a barrier preventing released compounds from diffusing freely in surrounding tissues. Together, oxidative processes and antigen containment allow the parasitized liver to cope with the dual threat posed by parasite eggs, i.e. a highly resistant chitinous eggshell and the release of toxic substances.

Bile salts modulate chronic ethanol-induced hepatotoxicity.

This study tested the hypothesis that chronic ethanol-induced injury in rats may be modified by the hydrophobicity of the bile acid pool. The supplementation to chronic ethanol feeding (28 days) with chenodeoxycholate, a hydrophobic bile salt, aggravated steatosis (accumulation of triacylglycerols and cholesterol esters), lipoperoxidation and cytolysis (expressed as elevations of activities of aspartate aminotransferase and glutamate dehydrogenase), while the addition of ursodeoxycholic acid, a hydrophilic bile salt, alleviated ethanol-induced hepatic alterations. Furthermore, our data show that ursodeoxycholic acid still exerts its beneficial effects in a model of more severe hepatic intoxication induced by the co-administration of ethanol and chenodeoxycholic acid. The hepato-protective effect observed appears to be independent of the choleretic properties of ursodeoxycholic acid and may be due partly to the capacity of the bile acid to preserve mitochondria.