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

Cir Esp. 2010 Jun;87(6):372-7. doi: 10.1016/j.ciresp.2010.03.009. Epub 2010 May 10.
[Article in Spanish]

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-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.

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.

Publication types

  • English Abstract
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cells, Cultured
  • Cytokines / immunology
  • Cytoprotection*
  • Immunosuppressive Agents / administration & dosage*
  • Immunosuppressive Agents / pharmacology
  • Islets of Langerhans / cytology*
  • Islets of Langerhans / drug effects*
  • Islets of Langerhans / immunology
  • Male
  • Rats
  • Rats, Wistar
  • Tacrolimus / administration & dosage*
  • Tacrolimus / pharmacology

Substances

  • Cytokines
  • Immunosuppressive Agents
  • Tacrolimus