Intestinal barrier function in response to abundant or depleted mucosal glutathione in Salmonella-infected rats.
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-1beta. 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.


CONCLUSIONS
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.
van Ampting
Marleen T J
MT
TI Food and Nutrition, Wageningen, the Netherlands. marleen.van.ampting@nizo.nl
Schonewille
Arjan J
AJ
Vink
Carolien
C
Brummer
Robert Jan M
RJ
van der Meer
Roelof
R
Bovee-Oudenhoven
Ingeborg M J
IM
D000818:Animals; D018988:Bacterial Translocation / Q000187:drug effects / Q000502:physiology*; D019328:Buthionine Sulfoximine / Q000494:pharmacology; D003553:Cystine / Q000008:administration & dosage / Q000494:pharmacology; D003967:Diarrhea / Q000209:etiology / Q000503:physiopathology; D004198:Disease Susceptibility; D005978:Glutathione / Q000037:antagonists & inhibitors / Q000502:physiology*; D007079:Ileitis / Q000503:physiopathology; D053583:Interleukin-1beta / Q000032:analysis; D007413:Intestinal Mucosa / Q000502:physiology*; D008070:Lipopolysaccharides / Q000633:toxicity; D008099:Liver / Q000378:metabolism; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress; D009195:Peroxidase / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D012481:Salmonella Infections, Animal / Q000150:complications / Q000382:microbiology / Q000503:physiopathology*; D012477:Salmonella enteritidis / Q000502:physiology; D013047:Specific Pathogen-Free Organisms
D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D009569:Nitric Oxide; D003553:Cystine; D019328:Buthionine Sulfoximine; D009195:Peroxidase; D005978:Glutathione