Possible Tacrolimus Action Mechanisms in Its Protector Effects on Ischemia-Reperfusion Injury

García-Criado, Francisco Javier; Lozano-Sanchez, Francisco; Fernandez-Regalado, Javier; Valdunciel-Garcia, J. J.; Parreno-Manchado, Felipe; Silva-Benito, Isabel; Zambrano-Cuadrado, Yolanda; Gómez‐Alonso, Alberto

doi:10.1097/00007890-199810150-00028

Cited by 17 publications

(14 citation statements)

References 11 publications

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“…23 Other studies have shown that tacrolimus pretreatment results in decreased expression of tumor necrosis factor-␣, IL-1, and IL-6. [23][24][25] More recently, it was documented to reduce expression of adhesion molecules, with a demonstrated reduction in leukocyte rolling and adhesion. 19 In conclusion, although complete elucidation of the role of tacrolimus in hepatic I/R injury deserves further investigation, in this trial, the first prospective randomized trial conducted in the clinical arena, we show that use of a flush solution containing tacrolimus results in superior early graft function and decreased hepatocellular injury.…”

Section: Discussionmentioning

confidence: 97%

“…22 In the cardiac model, tacrolimus has been shown to suppress nuclear factor-B and subsequently reduce leukocyte accumulation. 23 Investigations of hepatic ischemia found that tacrolimus administered before ischemia decreased interleukin-1 (IL-1) and tumor necrosis factor-␣ levels, as well as neutrophil migration. 23 Other studies have shown that tacrolimus pretreatment results in decreased expression of tumor necrosis factor-␣, IL-1, and IL-6.…”

Section: Discussionmentioning

confidence: 99%

“…23 Investigations of hepatic ischemia found that tacrolimus administered before ischemia decreased interleukin-1 (IL-1) and tumor necrosis factor-␣ levels, as well as neutrophil migration. 23 Other studies have shown that tacrolimus pretreatment results in decreased expression of tumor necrosis factor-␣, IL-1, and IL-6. [23][24][25] More recently, it was documented to reduce expression of adhesion molecules, with a demonstrated reduction in leukocyte rolling and adhesion.…”

Section: Discussionmentioning

confidence: 99%

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Tacrolimus as a liver flush solution to ameliorate the effects of ischemia/reperfusion injury following liver transplantation

Stella

2003

Liver Transplantation

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The goal of this report is to evaluate in a prospective randomized fashion the effect of flushing hepatic allografts with tacrolimus before transplantation. A prospective, double-blinded, randomized trial was performed. Twenty patients receiving orthotopic liver transplants from October 2000 to October 2001 were randomized into two groups. Group 1 (active) was administered tacrolimus, 20 ng/mL, plus Plasma-lyte A (Baxter Healthcare Corp, Deerfield, IL) liver flush solution; and group 2 (placebo) was administered only Plasma-lyte A. Ischemia/ reperfusion injury was assessed in both groups after transplantation by means of serum laboratory values to assess hepatocellular damage, synthetic function, and ion transport capacity. Peak values were recorded for each parameter, and their distributions were compared. There were no statistically significant differences between groups for age, sex, total ischemia time, or cause of liver disease. Global multivariate comparison of peak changes in all measures of liver function indicated liver injury was significantly lower with tacrolimus treatment than placebo (P ‫؍‬ .01). The sample median for group 1 was less than for group 2 in all parameters measured. Individual statistical comparison showed that peak changes from baseline aspartate aminotransferase and activated partial thromboplastin time values were significantly improved (P < .05) with tacrolimus treatment than placebo treatment. In this prospective, double-blinded, randomized trial, we show that flushing the liver before transplantation with Plasmalyte A containing tacrolimus results in superior early graft function and decreased hepatocellular injury after reperfusion compared with flushing with Plasma-lyte A alone. (Liver Transpl 2003;9:144-149.)

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Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Tacrolimus as a liver flush solution to ameliorate the effects of ischemia/reperfusion injury following liver transplantation

Stella

2003

Liver Transplantation

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“…65 More recently, tacrolimus has been documented to reduce expression of the adhesion molecules P-selectin and ICAM-1, with a reduction in leukocyte rolling and adhesion. 66 Tumor necrosis factor-␣ (TNF-␣) clearly is an important mediator of I-R injury. 67 Specifically, TNF-␣ has been documented to activate neutrophils to produce local damage during hepatic I-R injury.…”

Section: Cytokines and Intercellular Communicationmentioning

confidence: 99%

“…70 Some investigators suggested that PMN infiltration and the cumulative resultant free radical production are the most important mediators of I-R injury. 66,93 As discussed, expression of adhesion molecules on endothelial surfaces represents one of the initial steps leading to local PMN accumulation in injured tissue. Therefore, the demonstrated ability of tacrolimus to suppress cytokine release and adhesion molecule expression results in reduction of PMN infiltration and activation.…”

Section: Polymorphonuclear Neutrophilsmentioning

confidence: 99%

Effects of tacrolimus on ischemia-reperfusion injury

Stella

2003

Liver Transplantation

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In addition to efficacious immunosuppression for the benefit of organ transplantation, tacrolimus has diverse actions that result in amelioration of ischemia-reperfusion injury. Knowledge is accumulating rapidly on the mechanisms through which tacrolimus exerts these cytoprotective effects, including alterations in microcirculation, free radical metabolism, calcium-activated pathways, inflammatory cascades, mitochondrial stability, apoptosis, stress-response proteins, and tissue recovery. Within the nucleus, actions mediating the effects of tacrolimus appear to be dominantly influenced by interactions with the transcription factor, nuclear factor-B. Because tacrolimus is a cornerstone agent in immunosuppression regimens throughout the world and knowledge of its cellular mechanisms is evolving, it is important to update the clinical literature with this information. We reviewed the published literature with intent to portray the interactions of tacrolimus in the intricate cellular mechanisms initiated by ischemia and reperfusion. (Liver Transpl 2003;9: 105-116.)

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The immunosuppressant drug FK506 prevents Fas-induced apoptosis in human hepatocytes

Gómez‐Lechón¹,

Serralta

Donato³

et al. 2004

Biochemical Pharmacology

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Possible Tacrolimus Action Mechanisms in Its Protector Effects on Ischemia-Reperfusion Injury

Cited by 17 publications

References 11 publications

Tacrolimus as a liver flush solution to ameliorate the effects of ischemia/reperfusion injury following liver transplantation

Tacrolimus as a liver flush solution to ameliorate the effects of ischemia/reperfusion injury following liver transplantation

Effects of tacrolimus on ischemia-reperfusion injury

The immunosuppressant drug FK506 prevents Fas-induced apoptosis in human hepatocytes

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