Amelioration of renal ischaemia–reperfusion injury by liposomal delivery of curcumin to renal tubular epithelial and antigen‐presenting cells

Abstract

BACKGROUND AND PURPOSERenal 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-kB pathway. EXPERIMENTAL APPROACHWe utilized liposomal incorporation of a potent inhibitor of the NF-kB 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-kB activity and oxidative stress (histology, immunostaining) and for apoptosis (TUNEL). Cytokines and chemokines were measured by RT-PCR and Western blotting. KEY RESULTSLiposomal curcumin significantly improved serum creatinine, reduced histological injury and cellular apoptosis and lowered Toll-like receptor-4, heat shock protein-70 and TNF-a 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-kB, MAPK and phospho-S6 ribosomal protein. CONCLUSIONS AND IMPLICATIONSLiposomal 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.

Curcumin counteracts cisplatin-induced nephrotoxicity by preventing renal tubular cell apoptosis

“…On the other hand, recent studies have revealed that the antiapoptotic properties of curcumin against acute renal injury caused by ischemia/reperfusion 11,15 and gentamicin. 12 In this study, significant increases in serum urea and creatinine levels after exposure to cisplatin were accepted as an indicator of nephrotoxicity.…”

“…[8][9][10] Curcumin, a major component of turmeric, is known to have anti-inflammatory and antioxidant effects in various pathologies. [11][12][13][14][15][16][17] In addition, recent studies have revealed that the antiapoptotic properties of curcumin against different agent-mediated acute renal injury. 11,12,15 It has been reported that curcumin prevents and ameliorates the severity of cisplatin nephrotoxicity, by inhibiting various cytokines and chemokines such as TNF-a and IL-1b and scavenging free radicals.…”

“…[11][12][13][14][15][16][17] In addition, recent studies have revealed that the antiapoptotic properties of curcumin against different agent-mediated acute renal injury. 11,12,15 It has been reported that curcumin prevents and ameliorates the severity of cisplatin nephrotoxicity, by inhibiting various cytokines and chemokines such as TNF-a and IL-1b and scavenging free radicals. 4,14,[17][18][19] However, there is no any study to support the antiapoptotic effect of curcumin in cisplatininduced nephrotoxicity, yet.…”

Activation of Parenchymal CD47 Promotes Renal Ischemia-Reperfusion Injury

“…The difference between WT and knockout mice may have been greater if observed at an earlier time point (3-6 hours of reperfusion) that reflects the early phase development of apoptosis in IRI, 37 but apoptotic figures are typically evident at 24 hours of reperfusion. 38,39 The role of CD47 in programmed cell death has been defined in T cells through an interaction with BNIP3. 23 The involvement of CD47 in promoting apoptosis in other cell types has not been investigated, but the decreased RTEC apoptosis observed in CD47 2/2 mice may be explained by the proapoptotic function of CD47.…”

Lead Exposure in Different Organs of Mammals and Prevention by Curcumin–Nanocurcumin: a Review

“…Nanoparticles have the potential to evade recognition and uptake by the reticuloendothelial systems within the body and can flow into the blood for a longer time because of their small size, thereby via particle uptake mechanism drug bioavailability increase [70]. Nanocurcumin has many biological functions like anticancer action [71], anti-inflammatory action [72,73], antioxidative action [74][75][76], antiamyloid action [77,78], antimicrobial action [79], and antifibrotic action. Fibrosis refers to a condition in which the normal fibrous tissues of any organ are replaced by excessive and unnecessary invasion of fibrous connective tissues.…”