Research article

Intestinal barrier function in response to abundant or depleted mucosal glutathione in Salmonella-infected rats

Marleen TJ van Ampting^1,2 , Arjan J Schonewille^1,2 , Carolien Vink^1,2 , Robert Jan M Brummer^1,3,4 , Roelof van der Meer^1,2 and Ingeborg MJ Bovee-Oudenhoven^1,2

¹TI Food and Nutrition, Wageningen, the Netherlands

²Department of Health and Safety, NIZO food research, Ede, the Netherlands

³Nutrition and Toxicology Research institute Maastricht, Maastricht University, Maastricht, the Netherlands

⁴School of Health and Medical Sciences, Örebro University, Örebro, Sweden

author email corresponding author email

BMC Physiology 2009, 9:6doi:10.1186/1472-6793-9-6

Published:	17 April 2009

Abstract

Background

Glutathione, the main antioxidant of intestinal epithelial cells, is suggested to play an important role in gut barrier function and prevention of inflammation-related oxidative damage as induced by acute bacterial infection. Most studies on intestinal glutathione focus on oxidative stress reduction without considering functional disease outcome. Our aim was to determine whether depletion or maintenance of intestinal glutathione changes susceptibility of rats to Salmonella infection and associated inflammation.

Rats were fed a control diet or the same diet supplemented with buthionine sulfoximine (BSO; glutathione depletion) or cystine (glutathione maintenance). Inert chromium ethylenediamine-tetraacetic acid (CrEDTA) was added to the diets to quantify intestinal permeability. At day 4 after oral gavage with Salmonella enteritidis (or saline for non-infected controls), Salmonella translocation was determined by culturing extra-intestinal organs. Liver and ileal mucosa were collected for analyses of glutathione, inflammation markers and oxidative damage. Faeces was collected to quantify diarrhoea.

Results

Glutathione depletion aggravated ileal inflammation after infection as indicated by increased levels of mucosal myeloperoxidase and interleukin-1β. Remarkably, intestinal permeability and Salmonella translocation were not increased. Cystine supplementation maintained glutathione in the intestinal mucosa but inflammation and oxidative damage were not diminished. Nevertheless, cystine reduced intestinal permeability and Salmonella translocation.

Conclusion

Despite increased infection-induced mucosal inflammation upon glutathione depletion, this tripeptide does not play a role in intestinal permeability, bacterial translocation and diarrhoea. On the other hand, cystine enhances gut barrier function by a mechanism unlikely to be related to glutathione.