Role of Cellular Cholesterol in Pharmacologic Preconditioning with Cyclosporine in Experimental Kidney Transplantation
Autor: | Fuad S. Shihab, William M. Bennett, Takeshi F. Andoh |
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Rok vydání: | 2009 |
Předmět: |
Male
medicine.medical_specialty Indoles Kidney Cortex Time Factors Transplantation Conditioning Statin medicine.drug_class Ischemia Pharmacology Kidney Graft function Fatty Acids Monounsaturated chemistry.chemical_compound Internal medicine Cellular cholesterol medicine Animals Humans Fluvastatin Kidney transplantation Cholesterol business.industry Anticholesteremic Agents medicine.disease Kidney Transplantation Rats Inbred F344 Rats surgical procedures operative Endocrinology chemistry Nephrology Reperfusion Injury Cyclosporine business Reperfusion injury Immunosuppressive Agents |
Zdroj: | American Journal of Nephrology. 31:134-140 |
ISSN: | 1421-9670 0250-8095 |
Popis: | Background/Aims: Ischemia reperfusion injury in the early posttransplant period affects immediate graft function and late allograft dysfunction. Recently, we showed that pharmacologic preconditioning with a calcineurin inhibitor improved transplant outcomes in rat syngeneic kidney transplantation. There is also evidence that cellular cholesterol content increases after many types of renal injury. Methods: In this study, we looked at the effect of cyclosporine (CsA) on the donor kidney free cholesterol (FC) content in this model. Donor rats were pretreated with one dose of CsA 10 mg/kg administered 24 h or 7 days before being subjected to 2 h cold ischemia and then transplanted. Results: Pharmacologic preconditioning with CsA significantly improved renal function and histology and increased donor kidney FC content. On the other hand, fluvastatin co-administration with CsA abrogated that beneficial effect in association with a decrease in donor kidney FC content. Conclusion: CsA preconditioning leads to better outcomes in kidney transplantation and is associated with up-regulation of renal FC content. The latter may then contribute to acquired cytoresistance, possibly by stabilizing the plasma membrane. Thus, use of statins around the time of transplantation may need to be evaluated until further studies are conducted to determine the clinical relevance of this observation. |
Databáze: | OpenAIRE |
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