Inhibition of nitric oxide with aminoguanidine reduces bacterial translocation after endotoxin challenge in vivo

Donald L. Sorrells, Chris Friend, Ugur Koltuksuz, Anita Courcoulas, Patricia Boyle, Melissa Garrett, Simon Watkins, Marc I. Rowe, Henri Ford

Research output: Contribution to journalArticle

81 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)1155-1163
Number of pages9
JournalArchives of Surgery
Volume131
Issue number11
DOIs
StatePublished - Jan 1 1996
Externally publishedYes

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Bacterial Translocation
Endotoxins
Lipopolysaccharides
Nitric Oxide
Confocal Microscopy
Nitrites
Nitrates
Sodium Chloride
Membrane Potentials
pimagedine
Cecum
Enterocytes
Nitric Oxide Synthase Type II
Intestinal Mucosa
Fluorescein
Nitric Oxide Synthase
Sprague Dawley Rats
Permeability
Up-Regulation
Spleen

ASJC Scopus subject areas

  • 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 journalArticle

Sorrells, DL, Friend, C, Koltuksuz, U, Courcoulas, A, Boyle, P, Garrett, M, Watkins, S, Rowe, MI & Ford, H 1996, 'Inhibition of nitric oxide with aminoguanidine reduces bacterial translocation after endotoxin challenge in vivo', Archives of Surgery, vol. 131, no. 11, pp. 1155-1163. https://doi.org/10.1001/archsurg.1996.01430230037007
Sorrells, Donald L. ; Friend, Chris ; Koltuksuz, Ugur ; Courcoulas, Anita ; Boyle, Patricia ; Garrett, Melissa ; Watkins, Simon ; Rowe, Marc I. ; Ford, Henri. / Inhibition of nitric oxide with aminoguanidine reduces bacterial translocation after endotoxin challenge in vivo. In: Archives of Surgery. 1996 ; Vol. 131, No. 11. pp. 1155-1163.
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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.",
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AU - Boyle, Patricia

AU - Garrett, Melissa

AU - Watkins, Simon

AU - Rowe, Marc I.

AU - Ford, Henri

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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.

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