TY - JOUR
T1 - Cytoprotective effect of low-dose tacrolimus on islets of Langerhans in cultures subjected to stimulation by acute rejection cytokines
AU - Balibrea del Castillo, José María
AU - Arias-Díaz, Javier
AU - García Martín, María Cruz
AU - Vives-Pi, Marta
AU - García Pérez, Juan Carlos
AU - Cantero Cid, Ramón
AU - Vara Ameigeiras, Elena
AU - Balibrea Cantero, José Luis
PY - 2010/1/1
Y1 - 2010/1/1
N2 - 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.
AB - 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.
KW - Apoptosis
KW - Immunosuppression
KW - Oxidative stress
KW - Pancreatic islet transplantation
KW - Tacrolimus
UR - https://www.scopus.com/pages/publications/77953542506
U2 - 10.1016/j.ciresp.2010.03.009
DO - 10.1016/j.ciresp.2010.03.009
M3 - Article
SN - 0009-739X
VL - 87
SP - 372
EP - 377
JO - Cirugia Espanola
JF - Cirugia Espanola
IS - 6
ER -