Cytoprotective effect of low-dose tacrolimus on islets of Langerhans in cultures subjected to stimulation by acute rejection cytokines

José María Balibrea del Castillo, Javier Arias-Díaz, María Cruz García Martín, Marta Vives-Pi, Juan Carlos García Pérez, Ramón Cantero Cid, Elena Vara Ameigeiras, José Luis Balibrea Cantero

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4 Citations (Scopus)

Abstract

Introduction: 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. Aim: To evaluate in vitro islet low-dose tacrolimus response after pro-inflammatory stimulation. Material and methods: Isolated rat islets were cultured in RPMI medium in the presence of IL-1 (50. UI/mL) plus IF-γ (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/islet x 24. 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/islet x 24. h), nitric oxide (9.81. pmol/islet x 24. h) and Bcl-2 (1.37±0.23. UI/islet) were determined. Conclusion: 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. © 2009 AEC.
Original languageEnglish
Pages (from-to)372-377
JournalCirugia Espanola
Volume87
Issue number6
DOIs
Publication statusPublished - 1 Jan 2010

Keywords

  • Apoptosis
  • Immunosuppression
  • Oxidative stress
  • Pancreatic islet transplantation
  • Tacrolimus

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