title: Amelioration of renal ischaemia-reperfusion injury by liposomal delivery of curcumin to renal tubular epithelial and antigen-presenting cells.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors: Transplant Immunology Laboratory, Hanson Institute, Adelaide, SA, Australia.
authors: N M
authors: NM
authors: Rogers
authors: M D
authors: MD
authors: Stephenson
authors: A R
authors: AR
authors: Kitching
authors: J D
authors: JD
authors: Horowitz
authors: P T H
authors: PT
authors: Coates
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000494:pharmacology*; D000938:Antigen-Presenting Cells; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology; D015153:Blotting, Western; D018925:Chemokines / Q000378:metabolism; D003474:Curcumin / Q000008:administration & dosage / Q000494:pharmacology*; D016207:Cytokines / Q000378:metabolism; D016503:Drug Delivery Systems; D004847:Epithelial Cells / Q000187:drug effects / Q000473:pathology; D020287:In Situ Nick-End Labeling; D007684:Kidney Tubules / Q000166:cytology / Q000187:drug effects / Q000473:pathology; D008081:Liposomes; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000975:Antioxidants; D018925:Chemokines; D016207:Cytokines; D008081:Liposomes; D016328:NF-kappa B; D003474:Curcumin