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00925njm 22002777a 4500 dc Balibrea, José M. author García Martín, M. Cruz author Cuesta Sancho, Sara author Olmedilla, Yoko author Arias Díaz, Javier author Fernández Sevilla, Elena author Vara Ameigeiras, Elena María author Balibrea Cantero, José Luis author 2011-03-15 Cytoprotective effects of tacrolimus are due to its unspecific anti-inflammatory and anti-oxidant properties. Neither the exact mechanisms nor if there is any organ-specificity or dose-dependent response have not been yet elucidated. Our aim was to evaluate the effect of tacrolimus on oxidative stress and mediator production in liver and pancreatic tissue secondary to endotoxemia. Wistar rats were pretreated with intraperitoneal injection of tacrolimus (0.07, 0.15, and 0.3mg/kg) 24h before Escherichia coli LPS was administrated. Animals were sacrificed 24h after LPS administration and iNOS, eNOS, and nNOS and type 1 and 2 heme-oxygenase (HO) expression were measured. TNF-α and IL-1 tissue expression and plasmatic NO, CO, TNF-α, and IL-1 were also determined. LPS exposure increased iNOS expression in both organs, eNOS did not show variations and liver nNOS expression was significantly lower. Tacrolimus diminished both pancreas and liver iNOS and nNOS expression. Both liver and pancreatic eNOS expression augmented when tacrolimus was administrated. High doses of tacrolimus were correlated with ameliorated liver HO-1 plus HO-2 and pancreas HO-1 expression after LPS stimulation. Tacrolimus treatment diminished TNF-α but not IL-1 expression increase after LPS challenge in hepatic tissue. Pancreatic TNF-α and IL-1 values diminished partially when high doses were employed. Plasmatic NO, CO, TNF-α, and IL-1 concentrations increase after LPS challenge was diminished when highest doses of tacrolimus were given. In conclusion, tacrolimus exerts a protective effect on commonly observed harmful phenomena after LPS stimulation by modulating liver and pancreas oxidative enzyme expression and cytokine production Balibrea JM, García-Martín MC, Cuesta-Sancho S, Olmedilla Y, Arias-Díaz J, Fernández-Sevilla E, Vara E, Balibrea JL. Tacrolimus modulates liver and pancreas nitric oxide synthetase and heme-oxygenase isoforms and cytokine production after endotoxemia. Nitric Oxide. 2011 Mar 15;24(2):113-22. doi: 10.1016/j.niox.2011.01.002 1089-8603 10.1016/j.niox.2011.01.002 https://hdl.handle.net/20.500.14352/98326 https//doi.org/10.1016/j.niox.2011.01.002 https://pubmed.ncbi.nlm.nih.gov/21255669/ https://www.sciencedirect.com/science/article/pii/S1089860311000036?via%3Dihub Tacrolimus modulates liver and pancreas nitric oxide synthetase and heme-oxygenase isoforms and cytokine production after endotoxemia