title: [Cytoprotective effect of low-dose tacrolimus on islets of Langerhans in cultures subjected to stimulation by acute rejection cytokines].
abstract: BACKGROUND
  The improvement in pancreatic islet transplantation results is due to immunosuppression protocols that include, among others, low-dose tacrolimus. Both anti-inflammatory and anti-oxidant effects of tacrolimus could be useful in preventing primary rejection.
  
  
  OBJECTIVE
  To evaluate in vitro islet low-dose tacrolimus response after pro-inflammatory stimulation.
  
  
  METHODS
  Isolated rat islets were cultured in RPMI medium in the presence of IL-1 (50 UI/mL) plus IF-gamma (1000 UI/mL) and tacrolimus (5 ng/mL). The 24 h production of lipoperoxide (LPO) and nitric oxide (NO) were measured as oxidative stress markers. Determination of apoptosis markers (nucleosome content and Bcl-2) was also performed.
  
  
  RESULTS
  Oxidative stress (LPO 10.1+/-1.16 pmol/islet x 24; NO 19.1+/-3.28 pmol/isletx24 h) and apoptosis (nucleosome 0.24+/-0.04 UI/islet; Bcl-2 0.69+/-0.212 UI/islet) markers showed a very significant increase after cytokine stimulation (p<0.01). Both effects improved by adding tacrolimus to the medium. Protective effect was complete when lipoperoxide (1.58 pmol/isletx24 h), nitric oxide (9.81 pmol/isletx24 h) and Bcl-2 (1.37+/-0.23 UI/islet) were determined.
  
  
  CONCLUSIONS
  In vitro cytoprotective effect of low-dose tacrolimus on isolated rat islets decreases both oxidative stress and apoptosis markers after stimulation of pro-inflammatory mediators.
authors.affiliation: Servicio de Cirugía General y Digestiva, Hospital Universitario Germans Trias i Pujol, Departamento de Cirugía, Universidad Autónoma de Barcelona, Barcelona, Spain. balibrea@gmail.com
authors.forename: José María
authors.initials: JM
authors.lastname: Balibrea del Castillo
authors.forename: Javier
authors.initials: J
authors.lastname: Arias-Díaz
authors.forename: María Cruz
authors.initials: MC
authors.lastname: García Martín
authors.forename: Marta
authors.initials: M
authors.lastname: Vives-Pi
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: García Pérez
authors.forename: Ramón
authors.initials: R
authors.lastname: Cantero Cid
authors.forename: Elena
authors.initials: E
authors.lastname: Vara Ameigeiras
authors.forename: José Luis
authors.initials: JL
authors.lastname: Balibrea Cantero
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology; D019610:Cytoprotection; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000494:pharmacology; D007515:Islets of Langerhans / Q000166:cytology* / Q000187:drug effects* / Q000276:immunology; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D016559:Tacrolimus / Q000008:administration & dosage* / Q000494:pharmacology
chemical_list: D016207:Cytokines; D007166:Immunosuppressive Agents; D016559:Tacrolimus