Dose-response relationship and mechanism of action of Saccharomyces boulardii in castor oil-induced diarrhea in rats.
For biotherapeutic agents, there is a lack of information on dose-response relationships and mechanism of action. The present study was designed to address these issues for Saccharomyces boulardii using the rat model of castor oil-induced diarrhea. A single dose of Saccharomyces boulardii at 12 x 10(10) CFU/kg of viable cells given 1 hr before castor oil administration significantly reduced the onset of diarrhea. Repeated ingestion of the yeast, twice daily between 1.2 and 12 x 10(10) CFU/kg for 5 days before castor oil, showed a dose-response relationship. The percentage of rats with diarrhea decreased and a stronger protection was afforded by the repeated treatment. The mechanism of action of Saccharomyces boulardii in this model was investigated with two classes of antagonists, naloxone and L-arginine. The effect of Saccharomyces boulardii was not inhibited by naloxone but was significantly reduced by L-arginine. This last result suggests a novel mechanism of action for Saccharomyces boulardii involving a possible inhibition of nitric oxide production by the yeast.
Girard
Philippe
P
Laboratoires Biocodex, Service de Pharmacologie, Zac de Mercières 60200 Compiègne France.
Pansart
Yannick
Y
Lorette
Ingrid
I
Gillardin
Jean-Marie
JM
D000818:Animals; D000930:Antidiarrheals / Q000627:therapeutic use*; D001120:Arginine / Q000627:therapeutic use; D002368:Castor Oil; D003967:Diarrhea / Q000139:chemically induced / Q000628:therapy*; D004305:Dose-Response Relationship, Drug; D005657:Fungal Vaccines / Q000627:therapeutic use*; D007213:Indomethacin / Q000627:therapeutic use; D008139:Loperamide / Q000627:therapeutic use; D008297:Male; D009270:Naloxone / Q000627:therapeutic use; D019936:Probiotics / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D012440:Saccharomyces; D014882:Water-Electrolyte Balance / Q000187:drug effects
D000930:Antidiarrheals; D005657:Fungal Vaccines; C041317:ultra-levure; D009270:Naloxone; D008139:Loperamide; D002368:Castor Oil; D001120:Arginine; D007213:Indomethacin