title: Clostridium perfringens epsilon toxin increases the small intestinal permeability in mice and rats.
abstract: Epsilon toxin is a potent neurotoxin produced by Clostridium perfringens types B and D, an anaerobic bacterium that causes enterotoxaemia in ruminants. In the affected animal, it causes oedema of the lungs and brain by damaging the endothelial cells, inducing physiological and morphological changes. Although it is believed to compromise the intestinal barrier, thus entering the gut vasculature, little is known about the mechanism underlying this process. This study characterizes the effects of epsilon toxin on fluid transport and bioelectrical parameters in the small intestine of mice and rats. The enteropooling and the intestinal loop tests, together with the single-pass perfusion assay and in vitro and ex vivo analysis in Ussing's chamber, were all used in combination with histological and ultrastructural analysis of mice and rat small intestine, challenged with or without C. perfringens epsilon toxin. Luminal epsilon toxin induced a time and concentration dependent intestinal fluid accumulation and fall of the transepithelial resistance. Although no evident histological changes were observed, opening of the mucosa tight junction in combination with apoptotic changes in the lamina propria were seen with transmission electron microscopy. These results indicate that C. perfringens epsilon toxin alters the intestinal permeability, predominantly by opening the mucosa tight junction, increasing its permeability to macromolecules, and inducing further degenerative changes in the lamina propria of the bowel.
authors.affiliation: Laboratorio de Fisiopatogenia, Departamento de Fisiología, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina.
authors.forename: Jorge
authors.initials: J
authors.lastname: Goldstein
authors.forename: Winston E
authors.initials: WE
authors.lastname: Morris
authors.forename: César Fabián
authors.initials: CF
authors.lastname: Loidl
authors.forename: Carla
authors.initials: C
authors.lastname: Tironi-Farinati
authors.forename: Carla
authors.initials: C
authors.lastname: Tironi-Farinatti
authors.forename: Bruce A
authors.initials: BA
authors.lastname: McClane
authors.forename: Francisco A
authors.initials: FA
authors.lastname: Uzal
authors.forename: Mariano E
authors.initials: ME
authors.lastname: Fernandez Miyakawa
mesh_terms: D000818:Animals; D001427:Bacterial Toxins / Q000378:metabolism*; D004594:Electrophysiology; D020895:Enterocytes / Q000378:metabolism; D004767:Enterotoxemia / Q000382:microbiology*; D005260:Female; D007413:Intestinal Mucosa / Q000187:drug effects; D007421:Intestine, Small / Q000187:drug effects*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D046529:Microscopy, Electron, Transmission / Q000379:methods; D010539:Permeability / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D001427:Bacterial Toxins; C039811:Clostridium perfringens epsilon-toxin