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.
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