Curcumin-Loaded Nanoparticles Protect Against Rhabdomyolysis-Induced Acute Kidney Injury

Abstract

Background/Aims: Rhabdomyolysis (RM) is a potentially life-threatening condition that results from the breakdown of muscle and consequent release of toxic compounds into circulation. The most common and severe complication of RM is acute kidney injury (AKI). This study aimed to evaluate the efficacy and mechanisms of action of curcumin-loaded nanoparticles (Cur-NP) for treatment of RM-induced AKI. Methods: Curcumin-NP was synthesized using the nanocarrier distearoylphosphatidylethanolamine-polyethylene glycol (DSPE-PEG) to achieve a prolonged and constant drug release profile compared with the curcumin-free group. The anti-AKI effects of Curcumin-NP were examined both in vitro (myoglobin-treated renal tubular epithelial HK-2 cells) and in vivo (glycerol-induced AKI model). Results: Our results indicated that Curcumin-NP reversed oxidative stress, growth inhibition and cell apoptosis accompanied with down-regulation of apoptotic markers Caspase-3 and GRP-78 in vitro. In vivo studies revealed enhanced AKI treatment efficacy with Curcumin-NP as characterized by reduced serum creatine phosphokinase (CPK), creatinine (Cr) and urea and less severe histological damage in renal tubules. In addition, kidney tissues from Curcumin-NP-treated AKI rats exhibited reduced oxidative stress, apoptosis, and cleaved Capase-3 and GRP-78 expression. Conclusion: Our results suggest that nanoparticle-loaded curcumin enhances treatment efficacy for RM-induced AKI both in vitro and in vivo.

Programmed Cell-Death by Ferroptosis: Antioxidants as Mitigators

“…While oxidized phosphatidylethanolamines (PE) harboring arachidonoyl (AA) and adrenoyl moieties (AdA) have been shown to be proximate executioners of ferroptosis [13,14,19], the downstream molecular mechanisms of lipid peroxidation and ferroptosis (ultimate proteins or processes that damage membranes) are still conjectural and debatable. Several hypotheses have been proposed, and these include decreased cell membrane thickness and thinning, an accelerated influx of oxidants, destabilized membrane structure and fluidity leading to pore and micelle formation [19,20], promotion of lipid membrane perforation and pore formation [21,22], and the breakdown of lipid hydroperoxides to 4-hydroxy-2-nonenals (4-HNEs) or malondialdehydes (MDAs)—toxic aldehydes capable of crosslinking to undermine membrane structural integrity in ferroptosis [23]. The deleterious consequences of lipid peroxidation in ferroptosis are neutralized and nullified by natural and synthetic antioxidants and iron chelators [5,13].…”

Oxidative Stress and Renal Fibrosis: Recent Insights for the Development of Novel Therapeutic Strategies

“…Recently, berberine was reported to activate Nrf2 nuclear translocation and inhibit apoptosis of renal tubular epithelial cells induced by high glucose (Zhang et al, 2016 ). Curcumin from Curcuma Longa L. has well-documented anti-oxidant and renoprotective actions in several animal models of kidney injury, including Rhabdomyolysis-induced AKI (Chen X. et al, 2017 ), maleate-induced renal injury (Molina-Jijon et al, 2016 ), streptozotocin-induced diabetes (Ho et al, 2016 ), and the rat remnant kidney (Tapia et al, 2013 ). Recent evidence indicates that curcumin and its derivatives are potent hydrogen donors and may thus act primarily as chain breaking antioxidants, as opposed to direct free radical scavengers (Morales et al, 2015 ).…”

Microenvironment derived from metanephros transplantation inhibits the progression of acute kidney injury in glycerol-induced rat models

“…In this study, we selected a 15-day embryo kidney and transplanted it under the renal capsule of the recipient rats. Compared with the traditional methods, such as intravenous injection and intraperitoneal injection [36,37], subcapsular metanephroi transplantation can ensure the continuity of treatment of recipient kidney. Moreover, because the metanephroi microenvironment grows under the renal capsule, its protective effect on the kidney is more targeted.…”