Anti-inflammatory and antisecretory potential of histidine in Salmonella-challenged mouse small intestine

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Abstract

Challenge of mouse small intestinal loops with Salmonella typhimurium invoked the accumulation of luminal fluid, acute inflammation, and extensive structural damage to the small intestinal mucosa, as determined by histology and electron microscopy. Intraperitoneal and intestinal luminal injection of L-histidine, a known antioxidant, reduced the amount of fluid accumulating in the intestinal lumen and protected the intestinal tissue from S. typhimurium- induced damage. The reduction in S. typhimurium-induced fluid accumulation by L-histidine was specific for the L-enantiomer because D-histidine had no significant protective effect. Efficacy of L-histidine in protecting the infected intestinal tissue was attributed to the capacity of the imidazole ring to scavenge reactive oxygen species (ROS) generated by cells in the intestine during the acute inflammatory response. Glutathione levels were markedly reduced in S. typhimurium-challenged, inflamed intestinal tissues as a result of ROS generation. Importantly, after dosing the S. typhimurium- challenged mice with L-histidine, the glutathione content of the small intestinal tissue was not significantly different from mock-challenged controls. Further evidence favoring this mechanism included the capacity of L-histidine to scavenge ROS produced as a result of lipopolysaccharide (LPS) exposure of mononuclear cells (U937), as demonstrated with a redox-sensitive fluorescent dye (2'7'-dichlorodihydrofluorescein [DCF]). Addition of L- histidine, and to a lesser extent D-histidine, to the culture media of U937 cells before LPS exposure, resulted in a significant dose-dependent reduction in LPS-induced intracellular DCF fluorescence, as measured quantitatively by flow cytometry. The potential therapeutic value of anti-inflammatory drugs containing an L-histidine-like structure could protect infected mucosal tissues irrespective of microbial etiology.

Original languageEnglish (US)
Pages (from-to)523-534
Number of pages12
JournalLaboratory Investigation
Volume78
Issue number5
StatePublished - 1998

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Histidine
Salmonella
Small Intestine
Anti-Inflammatory Agents
Salmonella typhimurium
Lipopolysaccharides
Reactive Oxygen Species
U937 Cells
Glutathione
Gastrointestinal Contents
Intestinal Mucosa
Fluorescent Dyes
Oxidation-Reduction
Intestines
Culture Media
Histology
Electron Microscopy
Flow Cytometry
Mucous Membrane
Antioxidants

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

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title = "Anti-inflammatory and antisecretory potential of histidine in Salmonella-challenged mouse small intestine",
abstract = "Challenge of mouse small intestinal loops with Salmonella typhimurium invoked the accumulation of luminal fluid, acute inflammation, and extensive structural damage to the small intestinal mucosa, as determined by histology and electron microscopy. Intraperitoneal and intestinal luminal injection of L-histidine, a known antioxidant, reduced the amount of fluid accumulating in the intestinal lumen and protected the intestinal tissue from S. typhimurium- induced damage. The reduction in S. typhimurium-induced fluid accumulation by L-histidine was specific for the L-enantiomer because D-histidine had no significant protective effect. Efficacy of L-histidine in protecting the infected intestinal tissue was attributed to the capacity of the imidazole ring to scavenge reactive oxygen species (ROS) generated by cells in the intestine during the acute inflammatory response. Glutathione levels were markedly reduced in S. typhimurium-challenged, inflamed intestinal tissues as a result of ROS generation. Importantly, after dosing the S. typhimurium- challenged mice with L-histidine, the glutathione content of the small intestinal tissue was not significantly different from mock-challenged controls. Further evidence favoring this mechanism included the capacity of L-histidine to scavenge ROS produced as a result of lipopolysaccharide (LPS) exposure of mononuclear cells (U937), as demonstrated with a redox-sensitive fluorescent dye (2'7'-dichlorodihydrofluorescein [DCF]). Addition of L- histidine, and to a lesser extent D-histidine, to the culture media of U937 cells before LPS exposure, resulted in a significant dose-dependent reduction in LPS-induced intracellular DCF fluorescence, as measured quantitatively by flow cytometry. The potential therapeutic value of anti-inflammatory drugs containing an L-histidine-like structure could protect infected mucosal tissues irrespective of microbial etiology.",
author = "Johnny Peterson and Istvan Boldogh and Vsevolod Popov and Saini, {Shamsher S.} and Ashok Chopra",
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T1 - Anti-inflammatory and antisecretory potential of histidine in Salmonella-challenged mouse small intestine

AU - Peterson, Johnny

AU - Boldogh, Istvan

AU - Popov, Vsevolod

AU - Saini, Shamsher S.

AU - Chopra, Ashok

PY - 1998

Y1 - 1998

N2 - Challenge of mouse small intestinal loops with Salmonella typhimurium invoked the accumulation of luminal fluid, acute inflammation, and extensive structural damage to the small intestinal mucosa, as determined by histology and electron microscopy. Intraperitoneal and intestinal luminal injection of L-histidine, a known antioxidant, reduced the amount of fluid accumulating in the intestinal lumen and protected the intestinal tissue from S. typhimurium- induced damage. The reduction in S. typhimurium-induced fluid accumulation by L-histidine was specific for the L-enantiomer because D-histidine had no significant protective effect. Efficacy of L-histidine in protecting the infected intestinal tissue was attributed to the capacity of the imidazole ring to scavenge reactive oxygen species (ROS) generated by cells in the intestine during the acute inflammatory response. Glutathione levels were markedly reduced in S. typhimurium-challenged, inflamed intestinal tissues as a result of ROS generation. Importantly, after dosing the S. typhimurium- challenged mice with L-histidine, the glutathione content of the small intestinal tissue was not significantly different from mock-challenged controls. Further evidence favoring this mechanism included the capacity of L-histidine to scavenge ROS produced as a result of lipopolysaccharide (LPS) exposure of mononuclear cells (U937), as demonstrated with a redox-sensitive fluorescent dye (2'7'-dichlorodihydrofluorescein [DCF]). Addition of L- histidine, and to a lesser extent D-histidine, to the culture media of U937 cells before LPS exposure, resulted in a significant dose-dependent reduction in LPS-induced intracellular DCF fluorescence, as measured quantitatively by flow cytometry. The potential therapeutic value of anti-inflammatory drugs containing an L-histidine-like structure could protect infected mucosal tissues irrespective of microbial etiology.

AB - Challenge of mouse small intestinal loops with Salmonella typhimurium invoked the accumulation of luminal fluid, acute inflammation, and extensive structural damage to the small intestinal mucosa, as determined by histology and electron microscopy. Intraperitoneal and intestinal luminal injection of L-histidine, a known antioxidant, reduced the amount of fluid accumulating in the intestinal lumen and protected the intestinal tissue from S. typhimurium- induced damage. The reduction in S. typhimurium-induced fluid accumulation by L-histidine was specific for the L-enantiomer because D-histidine had no significant protective effect. Efficacy of L-histidine in protecting the infected intestinal tissue was attributed to the capacity of the imidazole ring to scavenge reactive oxygen species (ROS) generated by cells in the intestine during the acute inflammatory response. Glutathione levels were markedly reduced in S. typhimurium-challenged, inflamed intestinal tissues as a result of ROS generation. Importantly, after dosing the S. typhimurium- challenged mice with L-histidine, the glutathione content of the small intestinal tissue was not significantly different from mock-challenged controls. Further evidence favoring this mechanism included the capacity of L-histidine to scavenge ROS produced as a result of lipopolysaccharide (LPS) exposure of mononuclear cells (U937), as demonstrated with a redox-sensitive fluorescent dye (2'7'-dichlorodihydrofluorescein [DCF]). Addition of L- histidine, and to a lesser extent D-histidine, to the culture media of U937 cells before LPS exposure, resulted in a significant dose-dependent reduction in LPS-induced intracellular DCF fluorescence, as measured quantitatively by flow cytometry. The potential therapeutic value of anti-inflammatory drugs containing an L-histidine-like structure could protect infected mucosal tissues irrespective of microbial etiology.

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