Inducible nitric oxide synthase involvement in the mechanism of action of Saccharomyces boulardii in castor oil-induced diarrhoea in rats.
The biotherapeutic agent Saccharomyces boulardii has been shown to inhibit castor oil-induced diarrhoea in rats in a dose-response fashion, and one of the suggested mechanisms of action included involvement of the nitric oxide pathway. The present study was designed to address this mechanism of action by firstly measuring the effects of S. boulardii on the inducible nitric oxide synthase (iNOS) isoform activity in vitro. Second, the effects of S. boulardii on the increase in colonic citrulline level associated with castor oil treatment were examined. In vitro, S. boulardii showed a dose-dependent inhibition of iNOS activity with an IC50 of 0.89 mg/ml. In the rat diarrhoea model, the antidiarrhoeal effect of S. boulardii was confirmed using a single oral dose of 12 x 10(10) CFU/kg (viable cells). In this model, castor oil significantly elevated citrulline level from 2526+/-164 to 3501+/-193 nmol/g in the colon. When the rats were treated with the same antidiarrhoeal single dose of S. boulardii, no increase in citrulline level was observed. Moreover, the iNOS inhibitor 1400 W at 10 mg/kg and the inhibitor of iNOS expression dexamethasone at 1 mg/kg, administered subcutaneously, blocked the citrulline production induced by the laxative. Taken together, these findings confirm the involvement of inhibition of the inducible isoform of nitric oxide synthase in the mechanism of action of S. boulardii in diarrhoea.
Girard
Philippe
P
Biocodex, Service de Pharmacologie, Zac de Mercières, 60200 Compiègne, France. p.girard@biocodex.fr
Pansart
Yannick
Y
Gillardin
Jean-Marie
JM
D000818:Animals; D001691:Biological Therapy; D002368:Castor Oil / Q000633:toxicity*; D002956:Citrulline / Q000378:metabolism; D003106:Colon / Q000737:chemistry / Q000187:drug effects; D003967:Diarrhea / Q000139:chemically induced / Q000188:drug therapy*; D007527:Isoenzymes / Q000096:biosynthesis; D008297:Male; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis* / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D012440:Saccharomyces / Q000201:enzymology / Q000378:metabolism*
D007527:Isoenzymes; D002956:Citrulline; D002368:Castor Oil; D052247:Nitric Oxide Synthase Type II