title: Oral and systemic administration of beta-glucan protects against lipopolysaccharide-induced shock and organ injury in rats.
abstract: beta-Glucans are glucose polymers with a variety of stimulatory effects on the immune system. The objective of this study was to determine the effect of prophylactic oral administration of soluble Saccharomyces cerevisiae-derived beta-1,3/1,6-glucan (SBG) on the outcome of experimental endotoxaemia and shock-associated organ injury. Male Wistar rats were pretreated with SBG orally (SBGpo, 20 mg/kg/day) for 14 days, subcutaneously (SBGsc, 2 mg/kg/day) for 3 days, or vehicle (placebo). Rats were anaesthetized and subjected to endotoxaemia by intravenous infusion of Escherichia coli lipopolysaccharide (LPS) (6 mg/kg) or saline infusion (sham). We observed significant levels of plasma beta-glucan in the SBGpo group (P<0 x 5), although the SBGsc group had levels approximately 40-fold higher despite a 10-fold lower dose. SBG prophylaxis caused enhanced blood pressure recovery following LPS-induced blood pressure collapse. Oral treatment with SBG attenuated the LPS-induced rise in plasma creatinine levels (P<0 x 05), indicating protection against renal injury. SBG also attenuated the plasma levels of aspartate aminotransferase and alanine aminotransferase (SBGpo, P<0 x 01; SBGsc, P<0 x 01), indicating protection against LPS-induced hepatic injury. A moderate increase in baseline interleukin (IL)-1beta levels was observed in the SBGsc group (P< 0 x 05). In the LPS-challenged rats, plasma levels of proinflammatory cytokines was moderately reduced in both SBG-treated groups compared to placebo. SBG treatment, particularly oral administration, had a striking effect on the haemodynamics of LPS-treated rats, although only a minute fraction of the orally administered beta-glucan translocated to the circulation. Enhanced organ perfusion may thus be responsible for the attenuated levels of indicators of kidney and liver injury seen in SBG-treated rats.
authors.affiliation: Laboratory for Immunohistochemistry and Immunopathology, Institute of Pathology, Faculty Division, Rikshospitalet, University of Oslo, Oslo, Norway. anders.sandvik@medisin.uio.no
authors.forename: A
authors.initials: A
authors.lastname: Sandvik
authors.forename: Y Y
authors.initials: YY
authors.lastname: Wang
authors.forename: H C
authors.initials: HC
authors.lastname: Morton
authors.forename: A O
authors.initials: AO
authors.lastname: Aasen
authors.forename: J E
authors.initials: JE
authors.lastname: Wang
authors.forename: F-E
authors.initials: FE
authors.lastname: Johansen
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D016207:Cytokines / Q000097:blood; D019446:Endotoxemia / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control*; D007279:Injections, Subcutaneous; D008070:Lipopolysaccharides; D008297:Male; D009102:Multiple Organ Failure / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control*; D051381:Rats; D017208:Rats, Wistar; D012441:Saccharomyces cerevisiae; D012772:Shock, Septic / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control*; D047071:beta-Glucans / Q000008:administration & dosage* / Q000097:blood / Q000627:therapeutic use
chemical_list: D016207:Cytokines; D008070:Lipopolysaccharides; D047071:beta-Glucans