Amelioration of renal ischaemia-reperfusion injury by liposomal delivery of curcumin to renal tubular epithelial and antigen-presenting cells
| Autor: | N M, Rogers, M D, Stephenson, A R, Kitching, J D, Horowitz, P T H, Coates |
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| Rok vydání: | 2011 |
| Předmět: |
Male
Curcumin Time Factors Reverse Transcriptase Polymerase Chain Reaction Anti-Inflammatory Agents Non-Steroidal Blotting Western NF-kappa B Antigen-Presenting Cells Epithelial Cells Research Papers Antioxidants Mice Inbred C57BL Mice Oxidative Stress Drug Delivery Systems Kidney Tubules Reperfusion Injury Liposomes In Situ Nick-End Labeling Animals Cytokines Chemokines |
| Zdroj: | British journal of pharmacology. 166(1) |
| ISSN: | 1476-5381 |
| Popis: | Renal ischaemia-reperfusion (IR) injury is an inevitable consequence of renal transplantation, causing significant graft injury, increasing the risk of rejection and contributing to poor long-term graft outcome. Renal injury is mediated by cytokine and chemokine synthesis, inflammation and oxidative stress resulting from activation of the NF-κB pathway.We utilized liposomal incorporation of a potent inhibitor of the NF-κB pathway, curcumin, to target delivery to renal tubular epithelial and antigen-presenting cells. Liposomes containing curcumin were administered before bilateral renal ischaemia in C57/B6 mice, with subsequent reperfusion. Renal function was assessed from plasma levels of urea and creatinine, 4 and 24 h after reperfusion. Renal tissue was examined for NF-κB activity and oxidative stress (histology, immunostaining) and for apoptosis (TUNEL). Cytokines and chemokines were measured by RT-PCR and Western blotting.Liposomal curcumin significantly improved serum creatinine, reduced histological injury and cellular apoptosis and lowered Toll-like receptor-4, heat shock protein-70 and TNF-α mRNA expression. Liposomal curcumin also reduced neutrophil infiltration and diminished inflammatory chemokine expression. Curcumin liposomes reduced intracellular superoxide generation and increased superoxide dismutase levels, decreased inducible NOS mRNA expression and 3-nitrotyrosine staining consistent with limitations in nitrosative stress and inhibited renal tubular mRNA and protein expression of thioredoxin-interacting protein. These actions of curcumin were mediated by inhibition of NF-κB, MAPK and phospho-S6 ribosomal protein.Liposomal delivery of curcumin promoted effective, targeted delivery of this non-toxic compound that provided cytoprotection via anti-inflammatory and multiple antioxidant mechanisms following renal IR injury. |
| Databáze: | OpenAIRE |
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