title: Exogenous alkaline phosphatase treatment complements endogenous enzyme protection in colonic inflammation and reduces bacterial translocation in rats.
abstract: Alkaline phosphatase (AP) inactivates bacterial lipopolysaccharide and may therefore be protective. The small intestine and colon express intestinal (IAP) and tissue nonspecific enzyme (TNAP), respectively. The aim of this study was to assess the therapeutic potential of exogenous AP and its complementarity with endogenous enzyme protection in the intestine, as evidenced recently. IAP was given to rats by the oral or intrarectal route (700U/kgday). Oral budesonide (1mg/kgday) was used as a reference treatment. Treatment with intrarectal AP resulted in a 54.5% and 38.0% lower colonic weight and damage score, respectively, and an almost complete normalization of the expression of S100A8, LCN2 and IL-1β (p<0.05). Oral AP was less efficacious, while budesonide had a more pronounced effect on most parameters. Both oral and intrarectal AP counteracted bacterial translocation effectively (78 and 100%, respectively, p<0.05 for the latter), while budesonide failed to exert a positive effect. AP activity was increased in the feces of TNBS colitic animals, associated with augmented sensitivity to the inhibitor levamisole, suggesting enhanced luminal release of this enzyme. This was also observed in the mouse lymphocyte transfer model of chronic colitis. In a separate time course study, TNAP was shown to increase 2-3 days after colitis induction, while dextran sulfate sodium was a much weaker inducer of this isoform. We conclude that exogenous AP exerts beneficial effects on experimental colitis, which includes protection against bacterial translocation. AP of the tissue-nonspecific isoform is shed in higher amounts to the intestinal lumen in experimental colitis, possibly aiding in intestinal protection.
authors.affiliation: Department of Biochemistry and Molecular Biology II, School of Pharmacy, University of Granada, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas-CIBERehd, Campus de Cartuja s/n, 18071 Granada, Spain.
authors.forename: P
authors.initials: P
authors.lastname: Martínez-Moya
authors.forename: M
authors.initials: M
authors.lastname: Ortega-González
authors.forename: R
authors.initials: R
authors.lastname: González
authors.forename: A
authors.initials: A
authors.lastname: Anzola
authors.forename: B
authors.initials: B
authors.lastname: Ocón
authors.forename: C
authors.initials: C
authors.lastname: Hernández-Chirlaque
authors.forename: R
authors.initials: R
authors.lastname: López-Posadas
authors.forename: M D
authors.initials: MD
authors.lastname: Suárez
authors.forename: A
authors.initials: A
authors.lastname: Zarzuelo
authors.forename: O
authors.initials: O
authors.lastname: Martínez-Augustin
authors.forename: F
authors.initials: F
authors.lastname: Sánchez de Medina
mesh_terms: D000469:Alkaline Phosphatase / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D018988:Bacterial Translocation / Q000187:drug effects*; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy* / Q000201:enzymology; D004269:DNA, Bacterial / Q000032:analysis; D016264:Dextran Sulfate; D004195:Disease Models, Animal; D005243:Feces / Q000201:enzymology; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D008099:Liver / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D016513:Mice, SCID; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014302:Trinitrobenzenesulfonic Acid
chemical_list: D004269:DNA, Bacterial; D014302:Trinitrobenzenesulfonic Acid; D016264:Dextran Sulfate; D009195:Peroxidase; D000469:Alkaline Phosphatase