Evaluation of the preventative effects exerted by Lactobacillus fermentum in an experimental model of septic shock induced in mice.
The preventative effects of the probiotic Lactobacillus fermentum CECT5716 were evaluated in the lipopolysaccharide (LPS) model of septic shock in mice. The probiotic was administered suspended in drinking water at the final concentration of 108 colony-forming units/ml for 2 weeks before the induction of an endotoxic shock by an intraperitoneal injection of LPS (400 microg/200 microl per mouse). Blood and different organs were collected after 24 h to evaluate the severity of the endotoxic shock and the preventative effects of the probiotic. L. fermentum reduced TNF-alpha levels in blood, which promotes the major alterations observed during septic shock, as well as the infiltration of activated neutrophils into the lungs. Furthermore, free radical overproduction and oxidative stress were associated with a significant decrease in hepatic glutathione levels in septic mice, and with an excessive NO production attributed to the induction of the inducible isoform of NO synthase (iNOS). In fact, hepatic glutathione levels were significantly increased in the group of mice receiving the probiotic, and the increased iNOS expression both in the colon and lungs was down-regulated in those mice treated with L. fermentum. Finally, pre-treatment with L. fermentum may also exert its protective action modulating the expression of different cytokines in splenocyte-derived T cells such us IL-2, IL-5, IL-6 or IL-10. In conclusion, pre-treatment with L. fermentum may exert its protective action against LPS-induced organ damage in mice by a combination of several actions including its antioxidant properties and by reduction of the synthesis of the pro-inflammatory TNF-alpha and IL-6.
Arribas
Belén
B
Department of Pharmacology, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, University of Granada, Granada, Spain.
Rodríguez-Cabezas
Maria Elena
ME
Comalada
Mònica
M
Bailón
Elvira
E
Camuesco
Desireé
D
Olivares
Mónica
M
Xaus
Jordi
J
Zarzuelo
Antonio
A
Gálvez
Julio
J
D000818:Animals; D002478:Cells, Cultured; D004195:Disease Models, Animal; D052197:Limosilactobacillus fermentum; D008070:Lipopolysaccharides; D008168:Lung / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018375:Neutrophil Activation; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D019936:Probiotics / Q000627:therapeutic use*; D012772:Shock, Septic / Q000517:prevention & control*; D013154:Spleen / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000097:blood
D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D052247:Nitric Oxide Synthase Type II