Mitochondria‐mediated mitigatory role of curcumin in cisplatin‐induced nephrotoxicity

Abstract

Cisplatin (CP) is one of the most potent chemotherapeutic anti-tumour drugs, and it has been implicated in renal toxicity. Oxidative stress has been proven to be involved in CP-induced toxicity including nephrotoxicity. However, there is paucity of literature involving role of mitochondria in mediating CP-induced renal toxicity, and its underlying mechanism remains unclear. Therefore, the present study was undertaken to examine the antioxidant potential of curcumin (CMN; a natural polyphenolic compound) against the mitochondrial toxicity of CP in kidneys of male rats. Acute toxicity was induced by a single intra-peritoneal injection of CP (6 mg kg(-1) ). We studied the ameliorative effect of CMN pre-treatment (200 mg kg(-1) ) on the toxicity of CP in rat kidney mitochondria. CP caused a significant elevation in the mitochondrial lipid peroxidation (LPO) levels and protein carbonyl (PC) content. Pre-treatment of rat with CMN significantly replenished the mitochondrial LPO levels and PC content. It also restored the CP-induced modulatory effects on altered enzymatic and non-enzymatic antioxidants in kidney mitochondria. We hypothesize that the reno-protective effects of CMN may be related to its predisposition to scavenge free radicals, and upregulate antioxidant machinery in kidney mitochondria.

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

“…24 Curcumin has been regarded as a bifunctional antioxidant, in that it exerts direct scavenging activity on superoxide, hydroxyl, hydrogen peroxide, and peroxyl radicals, and also promotes the upregulation of various cytoprotective and antioxidant proteins (superoxide dismutase, catalase, and glutathione peroxidase). 4,26 In this study, the MDA levels, as an indicator of oxidative stress was elevated in kidney of rats exposure to cisplatin and curcumin treatment caused remarkable reduction in MDA levels, confirming the antioxidant effect of curcumin. Our findings are well matched with previous reports demonstrating similar effects of curcumin on renal damage induced by oxidative stress.…”

“…Control animals were treated with corn oil (a vehicle for curcumin) in the same way. The doses of curcumin 4 and cisplatin 20 were chosen on the basis of previously published studies. Forty-eight hours after cisplatin injection, under xylazine/ketamine anesthesia, cardiac blood and the right and left kidneys of all the animals were harvested.…”

“…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. Therefore, in this study, we evaluated the effects of curcumin on renal tubular cell apoptosis (the immunoreactivities of active caspase-3, Fas, Fas-L, and phospho-p53), in addition to inflammation [the levels of IL-1b, TNF-a, IL-6, IL-10, and myeloperoxidase (MPO)], lipid peroxidation [malondialdehyde (MDA)], and renal function (urea and creatinine levels) in cisplatin-mediated acute renal damage.…”

“…Previous studies have demonstrated the role of many interrelated factors involved in cisplatin-induced proximal tubular damage. These factors include a direct toxic effect on renal tubular cells, 2 DNA damage, 3 mitochondrial dysfunction, 4 apoptosis, 5 and autophagy. 6 Recent studies have focused on cisplatin-induced renal tubular cell apoptosis, and many apoptotic pathways, including tumor necrosis factor (TNF) receptors or the Fas-activated extrinsic pathway, the intrinsic mitochondrial pathway (Bax pathway) controlled by the Bcl-2 family, and the endoplasmic reticulum (ER) stress pathway, have been described as involved in renal tubular cell death.…”

Role of Curcumin as Anti-Oxidant in Nephrotoxicity

“…Cellular signalings such as inhibition of nuclear factor kappa-lightchain enhancer of activated B cells (NF-κB) [26,27] and decrease of macrophage infiltration [27] histone acetyltransferase p300 protein and oxidative stress [26] also these mechanisms may be as those, through which the curcumin protects against diabetic nephropathy. Also, Waseem M et al [28] at 2013 in a research has shown that curcumin could have protective effect in acute nephrotoxicity model induced with cisplatin in rat and reduced lipid peroxidation and protein carbonyl levels [28]. In Ukei M et al [29] study at 2013 in mice who received curcumin 10mg/kg with cisplatin has been shown, The levels of inflammation factors as tumor necrosis factor (TNF)-α and monocyte chemoattractant protein (MCP)-1 have been decreased [29].…”