Experimental acute alcohol pancreatitis-related liver damage and endotoxemia: synbiotics but not metronidazole have a protective effect.
OBJECTIVE
The aim of this study was to test the effect of gut manipulation by either novel synbiotics or by metronidazole on either endotoxemia or the severity of liver damage in the course of acute pancreatitis from alcohol ingestion.


METHODS
Sprague-Dawley rats were fed for 1 week through an intragastric tube a liquid diet with either: (i) 1 mL t.i.d. of a mixture of synbiotics (Lactobacillus acidophilus, Lactobacillus helveticus and Bifidobacterium in an enriched medium); (ii) 20 mg/kg t.i.d. metronidazole; or (iii) standard diet. Then, acute pancreatitis was induced by caerulein and when the disease was full-blown, rats were fed an alcohol-rich diet. Synbiotic and metronidazole treatment was given for a further 2 weeks. Transaminase and endotoxemia levels were measured before treatment, after 6 h, after 24 h and 2 weeks later, at the time the rats were killed. Liver samples were obtained for histological analysis.


RESULTS
Synbiotics but not metronidazole improved the acute pancreatitis-induced increase in endotoxemia and transaminase levels. The addition of alcohol worsened these variables to a limited extent in the synbiotic-treated group, while metronidazole had a negative effect on liver damage.


CONCLUSIONS
Gut flora pretreatment with synbiotics was able to effectively protect against endotoxin/bacterial translocation, as well as liver damage in the course of acute pancreatitis and concomitant heavy alcohol consumption. The beneficial effect of synbiotics on liver histology seems to be correlated with endotoxemia. Metronidazole did not produce such a beneficial effect; in fact, it further worsened liver damage when alcohol was added to the background of ongoing acute pancreatic inflammation.
Marotta
F
F
Hepato-Gastroenterology Department, S. Giuseppe Hospital, Milan, Italy. fmarchimede@libero.it
Barreto
R
R
Wu
C C
CC
Naito
Y
Y
Gelosa
F
F
Lorenzetti
A
A
Yoshioka
M
M
Fesce
E
E
D000208:Acute Disease; D000818:Animals; D018988:Bacterial Translocation / Q000187:drug effects; D001644:Bifidobacterium / Q000502:physiology; D002108:Ceruletide; D004195:Disease Models, Animal; D019446:Endotoxemia / Q000188:drug therapy* / Q000209:etiology; D004731:Endotoxins / Q000097:blood; D000431:Ethanol / Q000009:adverse effects; D041981:Gastrointestinal Tract / Q000382:microbiology; D007779:Lactobacillus acidophilus / Q000502:physiology; D052198:Lactobacillus helveticus / Q000502:physiology; D008108:Liver Diseases, Alcoholic / Q000188:drug therapy*; D008795:Metronidazole / Q000627:therapeutic use*; D010195:Pancreatitis / Q000139:chemically induced / Q000150:complications*; D019936:Probiotics / Q000627:therapeutic use*; D020011:Protective Agents / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D000637:Transaminases / Q000097:blood
D004731:Endotoxins; D020011:Protective Agents; D008795:Metronidazole; D000431:Ethanol; D002108:Ceruletide; D000637:Transaminases