Abstract
BackgroundGlutathione, 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.ResultsGlutathione 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.ConclusionDespite 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.
Highlights
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
Despite increased infection-induced mucosal inflammation upon glutathione depletion, this tripeptide does not play a role in intestinal permeability, bacterial translocation and diarrhoea
To mimic the composition of a Western human diet, the prepared diets were relatively low in calcium (30 mmol/kg) and high in fat content (200 g/kg) in comparison with recommendations for rodent diets by AIN-93. This control diet was supplemented with DLbuthionine(S, R)-sulfoximine (BSO) or L-cystine
Summary
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. Our aim was to determine whether depletion or maintenance of intestinal glutathione changes susceptibility of rats to Salmonella infection and associated inflammation. During foodborne Salmonella enteritidis infection pathogens can pass the gut epithelial cell lining and translocate to extra-intestinal organs like the spleen and liver[1]. In response to mucosal invasion of pathogens, epithelial cells and macrophages express pro-inflammatory cytokines, e.g. interleukin-1β (IL-1β), to recruit neutrophils[2,3] These efficient killers of translocating microbes [4] contain high concentrations of the enzyme myeloperoxidase (MPO)[4,5], which participates in the innate immune defence through formation of powerful reactive oxidants[4,5]. MPO is associated with oxidative stress-related damage (protein nitration) in the inflamed mucosa of ulcerative colitis patients[7]. Inhibition of MPO has even become a possible target of new drug development[8]
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