Lactic acid bacteria prevent alcohol-induced steatohepatitis in rats by acting on the pathways of alcohol metabolism.

The objective is to study the possible mechanism by which lactic acid bacteria (LAB) prevent alcohol-induced steatohepatitis in rats. A total of 25 Wistar rats were divided into three groups: a LAB-fed group, an alcohol-treated group and a control group. Both the LAB-fed group and the alcohol-treated group received alcohol (10 g kg(-1) per day) orally for up to 5 days (125 h). Before exposure to alcohol, the LAB-fed group were first treated daily with 1.5 ml/100 g of a mixture comprising 4 x 10(10) ml(-1) of Lactobacillus acidophilus and 2.5 x 10(7) ml(-1) of Bifidobacterium longum, while the control group was treated with normal saline only. Biochemical data, alcohol dehydrogenase (ADH) activity and histology of the liver and stomach were evaluated. The ADH activity in the LAB mixture was 3.52 +/- 0.45 mumol mg(-1) protein (10(9) CFU ml(-1)), and was dose-dependent. By 30 min after taking alcohol, serum alcohol concentrations were 514.24 +/- 80.21 microg ml(-1) in the LAB-fed group and 795.15 +/- 203.45 microg ml(-1) in the alcohol-treated group (P < 0.005). Serum alcohol concentrations were reduced by 48% (P < 0.01) in the LAB-fed group, but by only 4% in the alcohol-treated group (P > 0.05) 120 min after oral intake of alcohol. The blood levels of endotoxin, AST and ALT were improved in the LAB-fed group compared to the alcohol-fed group (P < 0.01). All alcohol-treated rats showed moderate to severe steatohepatitis, but the LAB-fed rats showed almost normal histology or very slight lesions only. In conclusion, LAB decreased the alcohol concentration in the blood by increasing the first-pass metabolism in both the stomach and the liver, and effectively protected against alcohol-induced gastric and liver injury. It is interesting to note that the protection was more effective in the liver.

P-selectin glycoprotein ligand-1 (rPSGL-Ig)-mediated blockade of CD62 selectin molecules protects rat steatotic liver grafts from ischemia/reperfusion injury.

We examined the effects of early blockade of CD62 selectin-mediated adhesive interactions in steatotic rat liver models of ex vivo cold ischemia followed by reperfusion or transplantation by administration of P-selectin glycoprotein ligand-1 (rPSGL-Ig). In the model of cold ischemia/reperfusion, livers pretreated ex vivo with rPSGL-Ig at harvesting from obese Zucker rats showed significantly decreased portal resistance, increased bile production, and diminished hepatic endothelial neutrophil infiltration, as compared with untreated controls. Pretreatment of fatty livers with rPSGL-Ig prior to transplantation extended the survival of lean Zucker rat recipients from 40% to 90%. This effect correlated with significantly improved liver function, depressed neutrophil activity, and decreased histologic features of hepatocyte injury. Intragraft expression of CD62 P-selectin was similar in both recipient groups. rPSGL-Ig treatment decreased intragraft infiltration by CD3/CD25 cells, diminished expression of pro-inflammatory TNFalpha, IL-6, iNOS, IL-2 and IFN-gamma, without significantly affecting mRNA levels coding for anti-inflammatory IL-4. Thus, rPSGL-Ig blockade of CD62-mediated adhesive interactions protects against severe ischemia/reperfusion injury suffered otherwise by steatotic rat livers. These findings document the potential utility of rPSGL-Ig in increasing the transplant donor pool through modulation of marginal steatotic livers.

Pharmacological studies on taurohyodeoxycholic acid.

In this study we investigated the anticholelithogenic and choleretic activities and the general pharmacological action of taurohyodeoxycholic acid (THDCA, Io, Praxis, CAS 2958-04-5), a new biliary acid advocated for use as anticholelithogenic agent. THDCA had no significant activity on the CNS (spontaneous locomotor activity, body temperature, coordinated movement, respiration); it also had no significant anticonvulsant or central anticholinergic actions. With regard to the action on the cardiovascular system, THDCA administration did not give rise to significant changes in blood pressure or ECG. Investigation of its action on the gastrointestinal system revealed no significant changes in the intestinal transport of charcoal after treatment. However, biliary flow and biliary solids content were increased by THDCA intraduodenal doses of 300 mg/kg b.w. In mice fed with lithogenic diet THDCA administration (230 and 450 mg/kg b.w. for 8 weeks) significantly decreased gallstone and steatosis incidence.