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Potential Therapeutic Effects of Mepacrine against Clostridium perfringens Enterotoxin in a Mouse Model of Enterotoxemia.
Navarro, Mauricio A; Shrestha, Archana; Freedman, John C; Beingesser, Juliann; McClane, Bruce A; Uzal, Francisco A.
Afiliación
  • Navarro MA; California Animal Health and Food Safety Laboratory System, School of Veterinary Medicine, University of California, Davis, San Bernardino, California, USA.
  • Shrestha A; Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
  • Freedman JC; Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
  • Beingesser J; California Animal Health and Food Safety Laboratory System, School of Veterinary Medicine, University of California, Davis, San Bernardino, California, USA.
  • McClane BA; Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
  • Uzal FA; California Animal Health and Food Safety Laboratory System, School of Veterinary Medicine, University of California, Davis, San Bernardino, California, USA fauzal@ucdavis.edu.
Infect Immun ; 87(4)2019 04.
Article en En | MEDLINE | ID: mdl-30642896
Clostridium perfringens enterotoxin (CPE) is a pore-forming toxin that causes the symptoms of common bacterial food poisoning and several non-foodborne human gastrointestinal diseases, including antibiotic-associated diarrhea and sporadic diarrhea. In some cases, CPE-mediated disease can be very severe or fatal due to the involvement of enterotoxemia. Therefore, the development of potential therapeutics against CPE action during enterotoxemia is warranted. Mepacrine, an acridine derivative drug with broad-spectrum effects on pores and channels in mammalian membranes, has been used to treat protozoal intestinal infections in human patients. A previous study showed that the presence of mepacrine inhibits CPE-induced pore formation and activity in enterocyte-like Caco-2 cells, reducing the cytotoxicity caused by this toxin in vitro Whether mepacrine is similarly protective against CPE action in vivo has not been tested. When the current study evaluated whether mepacrine protects against CPE-induced death and intestinal damage using a murine ligated intestinal loop model, mepacrine protected mice from the enterotoxemic lethality caused by CPE. This protection was accompanied by a reduction in the severity of intestinal lesions induced by the toxin. Mepacrine did not reduce CPE pore formation in the intestine but inhibited absorption of the toxin into the blood of some mice. Protection from enterotoxemic death correlated with the ability of this drug to reduce CPE-induced hyperpotassemia. These in vivo findings, coupled with previous in vitro studies, support mepacrine as a potential therapeutic against CPE-mediated enterotoxemic disease.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Quinacrina / Infecciones por Clostridium / Clostridium perfringens / Enterotoxemia / Enterotoxinas / Antibacterianos Tipo de estudio: Prognostic_studies Límite: Animals / Female / Humans / Male Idioma: En Revista: Infect Immun Año: 2019 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Quinacrina / Infecciones por Clostridium / Clostridium perfringens / Enterotoxemia / Enterotoxinas / Antibacterianos Tipo de estudio: Prognostic_studies Límite: Animals / Female / Humans / Male Idioma: En Revista: Infect Immun Año: 2019 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos