PURPOSE: Warm-ischemia-induced injuries might be encountered during renal transplants from cadavers and healthy donors. Toll-like receptors (TLR) in ischemia-reperfusion (I/R) injury are one of the indicators of intracellular injury pathways. The intensity of ischemic injury is directly proportionate to high TLR levels. To minimize the I/R injury, we investigated TLR2 and TLR4 levels on rats, which were pretreated with tacrolimus (FK506) before I/R. METHODS: Eight Wistar albino rats in the study group were administered .01 mg/kg intramuscular tacrolimus. Administration to the study group was performed 24 and 1 h before warm ischemia. Eight rats in the control group were injected with 0.1 c.c. of distilled water. Blood samples were collected from the tail veins of all the rats on the first, second and third days. Expression levels of TLR2 and TLR4 genes were analyzed using the polymerase chain reaction method, to determine any significant difference between the control and study groups on the days when blood was taken. RESULTS: TLR2 (p = 0.045) and TLR4 (p = 0.022) levels in the study group were found to be statistically, and significantly, lower than those in the control group, on the second day following warm-ischemia- and reperfusion-induced injury. CONCLUSIONS: Administration of immunosuppressive drugs to healthy donor rats led to a statistically significant reduction in the expression levels of TLR2 and TLR4 in the early period. In light of the data obtained by this study, we hypothesize that a preoperative therapy on donors might have a role in preventing I/R injury.
PURPOSE: Warm-ischemia-induced injuries might be encountered during renal transplants from cadavers and healthy donors. Toll-like receptors (TLR) in ischemia-reperfusion (I/R) injury are one of the indicators of intracellular injury pathways. The intensity of ischemic injury is directly proportionate to high TLR levels. To minimize the I/R injury, we investigated TLR2 and TLR4 levels on rats, which were pretreated with tacrolimus (FK506) before I/R. METHODS: Eight Wistar albino rats in the study group were administered .01 mg/kg intramuscular tacrolimus. Administration to the study group was performed 24 and 1 h before warm ischemia. Eight rats in the control group were injected with 0.1 c.c. of distilled water. Blood samples were collected from the tail veins of all the rats on the first, second and third days. Expression levels of TLR2 and TLR4 genes were analyzed using the polymerase chain reaction method, to determine any significant difference between the control and study groups on the days when blood was taken. RESULTS:TLR2 (p = 0.045) and TLR4 (p = 0.022) levels in the study group were found to be statistically, and significantly, lower than those in the control group, on the second day following warm-ischemia- and reperfusion-induced injury. CONCLUSIONS: Administration of immunosuppressive drugs to healthy donorrats led to a statistically significant reduction in the expression levels of TLR2 and TLR4 in the early period. In light of the data obtained by this study, we hypothesize that a preoperative therapy on donors might have a role in preventing I/R injury.
Authors: G Grosso; D Corona; A Mistretta; D Zerbo; N Sinagra; A Giaquinta; S Cimino; B Ekser; G Giuffrida; A Leonardi; R Gula; P Veroux; M Veroux Journal: Transplant Proc Date: 2012-09 Impact factor: 1.066
Authors: Ron Shapiro; Demetrius Ellis; Henkie P Tan; Michael L Moritz; Amit Basu; Abhay N Vats; Akhtar S Khan; Edward A Gray; Adrianna Zeevi; Corde McFeaters; Gerri James; Mary Jo Grosso; Amadeo Marcos; Thomas E Starzl Journal: J Pediatr Date: 2006-06 Impact factor: 4.406
Authors: F X Zhang; C J Kirschning; R Mancinelli; X P Xu; Y Jin; E Faure; A Mantovani; M Rothe; M Muzio; M Arditi Journal: J Biol Chem Date: 1999-03-19 Impact factor: 5.157
Authors: Bernd Krüger; Stefanie Krick; Navdeep Dhillon; Susan M Lerner; Scott Ames; Jonathan S Bromberg; Marvin Lin; Liron Walsh; John Vella; Michael Fischereder; Bernhard K Krämer; Robert B Colvin; Peter S Heeger; Barbara T Murphy; Bernd Schröppel Journal: Proc Natl Acad Sci U S A Date: 2009-02-13 Impact factor: 11.205