Abstract
Background: Administration of lipopolysaccharide (LPS) has been shown to increase bacterial translocation (BT) in vivo and in vitro. In addition, LPS upregulates inducible nitric oxide synthase expression in the intestinal epithelium-a phenomenon that can either enhance microbial killing, or alternatively, promote BT by impairing the gut barrier. Objective: To determine the effect, if any, of an inhibitor of nitric oxide synthase, namely, aminoguanidine (AG), on BT after LPS challenge. Design: Sprague- Dawley rats were randomized to receive either AG or normal saline solution via subcutaneously placed osmotic pumps (Alzet), followed 18 hours later by LPS injection (5 mg/kg or 20 mg/kg intraperitoneally). Quantitative cultures of the cecum, mesenteric lymph nodes, liver, and spleen were obtained, and plasma nitrite and nitrate levels were measured at 24 hours. Transmembrane potential difference and mucosal permeability to fluorescein isothiocyanate- labeled dextran and fluorescein isothiocyanate-labeled Escherichia coli C25 were measured in the Ussing chamber. The intestinal membrane was examined by light, transmission electron, and confocal laser microscopy. Results: Rats that were given high-dose LPS had elevated levels of nitrite and nitrate and a 100% incidence of BT. In contrast, AG infusion significantly reduced both BT (22%) and nitrite and nitrate levels. Animals that received LPS and normal saline solution had a significantly lower transmembrane potential difference than those that received LPS and AG. High-dose LPS resulted in sloughing of the apical enterocytes at the villus tips where bacterial entry seemed to occur, as seen with confocal laser microscopy. Conclusions: Inhibition of nitric oxide production with AG decreases BT after high-dose LPS challenge. The mechanism may involve increased cellular viability and decreased damage to the gut mucosal barrier in rats that receive AG.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1155-1163 |
| Number of pages | 9 |
| Journal | Archives of Surgery |
| Volume | 131 |
| Issue number | 11 |
| DOIs | |
| State | Published - Jan 1 1996 |
| Externally published | Yes |
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- Surgery
Cite this
Inhibition of nitric oxide with aminoguanidine reduces bacterial translocation after endotoxin challenge in vivo. / Sorrells, Donald L.; Friend, Chris; Koltuksuz, Ugur; Courcoulas, Anita; Boyle, Patricia; Garrett, Melissa; Watkins, Simon; Rowe, Marc I.; Ford, Henri.
In: Archives of Surgery, Vol. 131, No. 11, 01.01.1996, p. 1155-1163.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Inhibition of nitric oxide with aminoguanidine reduces bacterial translocation after endotoxin challenge in vivo
AU - Sorrells, Donald L.
AU - Friend, Chris
AU - Koltuksuz, Ugur
AU - Courcoulas, Anita
AU - Boyle, Patricia
AU - Garrett, Melissa
AU - Watkins, Simon
AU - Rowe, Marc I.
AU - Ford, Henri
PY - 1996/1/1
Y1 - 1996/1/1
N2 - Background: Administration of lipopolysaccharide (LPS) has been shown to increase bacterial translocation (BT) in vivo and in vitro. In addition, LPS upregulates inducible nitric oxide synthase expression in the intestinal epithelium-a phenomenon that can either enhance microbial killing, or alternatively, promote BT by impairing the gut barrier. Objective: To determine the effect, if any, of an inhibitor of nitric oxide synthase, namely, aminoguanidine (AG), on BT after LPS challenge. Design: Sprague- Dawley rats were randomized to receive either AG or normal saline solution via subcutaneously placed osmotic pumps (Alzet), followed 18 hours later by LPS injection (5 mg/kg or 20 mg/kg intraperitoneally). Quantitative cultures of the cecum, mesenteric lymph nodes, liver, and spleen were obtained, and plasma nitrite and nitrate levels were measured at 24 hours. Transmembrane potential difference and mucosal permeability to fluorescein isothiocyanate- labeled dextran and fluorescein isothiocyanate-labeled Escherichia coli C25 were measured in the Ussing chamber. The intestinal membrane was examined by light, transmission electron, and confocal laser microscopy. Results: Rats that were given high-dose LPS had elevated levels of nitrite and nitrate and a 100% incidence of BT. In contrast, AG infusion significantly reduced both BT (22%) and nitrite and nitrate levels. Animals that received LPS and normal saline solution had a significantly lower transmembrane potential difference than those that received LPS and AG. High-dose LPS resulted in sloughing of the apical enterocytes at the villus tips where bacterial entry seemed to occur, as seen with confocal laser microscopy. Conclusions: Inhibition of nitric oxide production with AG decreases BT after high-dose LPS challenge. The mechanism may involve increased cellular viability and decreased damage to the gut mucosal barrier in rats that receive AG.
AB - Background: Administration of lipopolysaccharide (LPS) has been shown to increase bacterial translocation (BT) in vivo and in vitro. In addition, LPS upregulates inducible nitric oxide synthase expression in the intestinal epithelium-a phenomenon that can either enhance microbial killing, or alternatively, promote BT by impairing the gut barrier. Objective: To determine the effect, if any, of an inhibitor of nitric oxide synthase, namely, aminoguanidine (AG), on BT after LPS challenge. Design: Sprague- Dawley rats were randomized to receive either AG or normal saline solution via subcutaneously placed osmotic pumps (Alzet), followed 18 hours later by LPS injection (5 mg/kg or 20 mg/kg intraperitoneally). Quantitative cultures of the cecum, mesenteric lymph nodes, liver, and spleen were obtained, and plasma nitrite and nitrate levels were measured at 24 hours. Transmembrane potential difference and mucosal permeability to fluorescein isothiocyanate- labeled dextran and fluorescein isothiocyanate-labeled Escherichia coli C25 were measured in the Ussing chamber. The intestinal membrane was examined by light, transmission electron, and confocal laser microscopy. Results: Rats that were given high-dose LPS had elevated levels of nitrite and nitrate and a 100% incidence of BT. In contrast, AG infusion significantly reduced both BT (22%) and nitrite and nitrate levels. Animals that received LPS and normal saline solution had a significantly lower transmembrane potential difference than those that received LPS and AG. High-dose LPS resulted in sloughing of the apical enterocytes at the villus tips where bacterial entry seemed to occur, as seen with confocal laser microscopy. Conclusions: Inhibition of nitric oxide production with AG decreases BT after high-dose LPS challenge. The mechanism may involve increased cellular viability and decreased damage to the gut mucosal barrier in rats that receive AG.
UR - http://www.scopus.com/inward/record.url?scp=0029960729&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0029960729&partnerID=8YFLogxK
U2 - 10.1001/archsurg.1996.01430230037007
DO - 10.1001/archsurg.1996.01430230037007
M3 - Article
C2 - 8911255
AN - SCOPUS:0029960729
VL - 131
SP - 1155
EP - 1163
JO - JAMA Surgery
JF - JAMA Surgery
SN - 2168-6254
IS - 11
ER -