[Bile acids and their derivatives. IV. A new method of gradual breakdown; its application to the degradation of lithocholic acid].
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BACKGROUND: Tauroursodeoxycholic acid (TUDC) is a hydrophilic bile acid that has a cytoprotective effect in primary biliary cirrhosis and primary sclerosing cholangitis. TUDC also protects hepatocytes from hydrophobic bile acid-induced apoptosis. The aim of this study was to determine whether TUDC ameliorates hepatocyte apoptosis during ischemia-reperfusion injury. METHODS: We used a rat model of hepatic warm ischemia-reperfusion injury to assess the effects of TUDC. Male Sprague-Dawley rats were subjected to 1 or 2 hr of normothermic ischemia followed by 3 or 6 hr of reperfusion. The treatment group received TUDC (50 mg/kg) by bolus intravenous injection 30 min before initiation of ischemia, whereas the control group received saline only. Blood samples for biochemical analysis were obtained after 6 hr of reperfusion. Liver biopsies for histological assessment were obtained 3 and 6 hr after reperfusion. Hepatocyte apoptosis was determined by terminal dUTP nick-end labeling. The pro-apoptotic protein Bax was quantified at the mRNA and protein level. RESULTS: Treatment with TUDC significantly reduced serum transaminase levels. This was associated with a significant amelioration in the levels of hepatocyte apoptosis in the TUDC-treated group compared with control. Furthermore, Western blot analysis of Bax expression in liver tissue indicated that TUDC inhibited the translocation of Bax from the cytosol to the mitochondria. CONCLUSIONS: TUDC significantly reduced hepatic injury in this model. The beneficial effects of TUDC upon hepatocyte apoptosis were related to the modulation of Bax protein translocation.
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Prevention of acute gastric erosions with histamine H2-receptor blocking agents suggests that these drugs may improve the ability of the gastric mucosa to maintain electrical, ionic, and protein concentration gradients. In 5 awake mongrel dogs, transmural potential difference, ion fluxes, and protein loss were measured across Heidenhain pouches topically exposed to isotonic solutions containing either 80 mM HCl or 80 mM HCl plus 20 mM sodium taurocholate (BS). The dogs received an intravenous infusion of either saline (as a control) or the H2 antagonist metiamide, 10 mumoles per kg-hr. Metiamide increased the H+ clearance rate found after acid test solution exposure but had no significant effect on potential difference or ion fluxes. H2 antagonism decreased the protein loss but not the increase in cation permeability due to BS. Net H+ loss actually increased, which, along with a decrease in Cl- gain, suggests inhibition of acid secretion by metiamide in BS-exposed gastric mucosa. These effects of metiamide point to histamine as a likely mediator of the gastric mucosal damage due to BS.
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When exponential phase cultures of Lactococcus lactis were directly exposed to severe stresses (acid, bile salt, heat, and hydrogen peroxide) for a prolonged period, most of the cells were quickly killed, however, a small number of the cells, approximately 0.01% of the population, was found to survive. How these 'survivor' cells might have survived the stresses, when other supposedly-the-same cells could not, was investigated. The cultures were not exposed to any mild stresses prior to the exposure to the severe stresses, and therefore adaptation can be ruled out as the cause of survival. When the survivor cells were re-cultured and re-exposed to the same severe stresses a similar pattern of survival was displayed, indicating that the survivor cells were not stress-resistant mutants. Furthermore, the survivor cells displayed typical growth kinetics once they were freed of the stresses. The survivor cells appear to be in a distinct physiological state, because when they were tested against a second stress they exhibited significantly greater survival against that stress than the normal cells exposed to the same stress. Also, cells at different time points of synchronously growing culture displayed different levels of survival against stress. It is proposed that the difference in survival of exponential phase cells is due to the difference in the protein makeup of cells at different stages of the cell cycle.
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