title: The Bisphosphonate Pamidronate is an Intestinal Antiinflammatory Agent in Rat and Mouse Experimental Colitis.
abstract: Statins have antiinflammatory effects at the cardiovascular level because of inhibition of prenylation, which also probably underlies their therapeutic effects in preclinical models of inflammatory bowel disease. Another inhibitor of prenylation, namely alendronate, reduces colitis in rodents. In this study, we aim to explore the therapeutic potential of second-generation, nitrogen-containing bisphosphonates in 3 preclinical models of colitis.
  
  
  
  The trinitrobenzenesulfonic acid and dextran sulfate sodium models of rat colitis and the adoptive lymphocyte transfer model of colitis in mice were used. Pamidronate, alendronate, and ibandronate were tested. Treatments were administered in equimolar doses through the oral or intraperitoneal route. The effect of pamidronate on prenylation and cytokine release was assessed in vivo and in vitro.
  
  
  
  Pretreatment with pamidronate, but not with ibandronate or alendronate, improves chemically induced trinitrobenzenesulfonic acid and dextran sulfate sodium colitis in rats. Moreover, this beneficial effect is extended to lymphocyte transfer colitis. Pamidronate has no effect on intestinal epithelial cells in vitro in terms of cytokine/chemokine release, but enhances IFN-γ, IL-6, and IL-10 production by T cells in coculture. Pamidronate also exerts a direct immunomodulatory effect on T cells, favoring Th1 differentiation and impairing Th17 polarization.
  
  
  
  Pamidronate presents antiinflammatory and immunomodulatory properties in 3 different models of experimental colitis in rodents. This effect requires oral administration and may involve T cells in the gut mucosa, although the exact mechanism is unclear.
authors.affiliation: *Department of Pharmacology, CIBERehd, School of Pharmacy, Instituto de Investigación Biosanitaria ibs.GRANADA, University of Granada; Dr. Rocío López-Posadas is now with the Medical Clinic 1, Translational Research Center, University Hospital, University of Erlangen-Nuremberg, Erlangen, Germany; Dr. Cristina Mascaraque is now with the IBD Center, Humanitas Clinical and Research Center, Rozzano, Milan, Italy; and†Department of Biochemistry and Molecular Biology II, CIBERehd, School of Pharmacy, Instituto de Investigación Biosanitaria ibs.GRANADA, University of Granada, Granada, Spain.
authors.forename: Rocío
authors.initials: R
authors.lastname: López-Posadas
authors.forename: Cristina
authors.initials: C
authors.lastname: Mascaraque
authors.forename: Raquel
authors.initials: R
authors.lastname: González
authors.forename: María D
authors.initials: MD
authors.lastname: Suárez
authors.forename: Antonio
authors.initials: A
authors.lastname: Zarzuelo
authors.forename: Olga
authors.initials: O
authors.lastname: Martínez-Augustin
authors.forename: Fermín
authors.initials: F
authors.lastname: Sánchez de Medina
mesh_terms: D019386:Alendronate / Q000008:administration & dosage; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy*; D016264:Dextran Sulfate; D004164:Diphosphonates / Q000008:administration & dosage*; D000077557:Ibandronic Acid; D007155:Immunologic Factors / Q000008:administration & dosage*; D007413:Intestinal Mucosa / Q000187:drug effects; D051379:Mice; D000077268:Pamidronate; D051381:Rats; D013601:T-Lymphocytes / Q000187:drug effects; D014302:Trinitrobenzenesulfonic Acid
chemical_list: D000893:Anti-Inflammatory Agents; D004164:Diphosphonates; D007155:Immunologic Factors; D014302:Trinitrobenzenesulfonic Acid; D016264:Dextran Sulfate; D000077268:Pamidronate; D000077557:Ibandronic Acid; D019386:Alendronate