Curcumin prevents cisplatin-induced decrease in the tight and adherens junctions: relation to oxidative stress

Abstract

Curcumin is a polyphenol and cisplatin is an antineoplastic agent that induces nephrotoxicity associated with oxidative stress, apoptosis, fibrosis and decrease in renal tight junction (TJ) proteins. The potential effect of curcumin against alterations in TJ structure and function has not been evaluated in cisplatin-induced nephrotoxicity. The present study explored whether curcumin is able to prevent the cisplatin-induced fibrosis and decreased expression of the TJ and adherens junction (AJ) proteins occludin, claudin-2 and E-cadherin in cisplatin-induced nephrotoxicity. Curcumin (200 mg kg(-1)) was administered in three doses, and rats were sacrificed 72 h after cisplatin administration. Curcumin was able to scavenge, in a concentration-dependent way, superoxide anion, hydroxyl radical, peroxyl radical, singlet oxygen, peroxynitrite anion, hypochlorous acid and hydrogen peroxide. Cisplatin-induced renal damage was associated with alterations in plasma creatinine, expression of neutrophil gelatinase-associated lipocalin and of kidney injury molecule-1, histological damage, increase in apoptosis, fibrosis (evaluated by transforming growth factor β1, collagen I and IV and α-smooth muscle actin expressions), increase in oxidative/nitrosative stress (evaluated by Hsp70/72 expression, protein tyrosine nitration, superoxide anion production in isolated glomeruli and proximal tubules, and protein levels of NADPH oxidase subunits p47(phox) and gp91(phox), protein kinase C β2, and Nrf2) as well as by decreased expression of occludin, claudin-2, β-catenin and E-cadherin. Curcumin treatment prevented all the above-described alterations. The protective effect of curcumin against cisplatin-induced fibrosis and decreased proteins of the TJ and AJ was associated with the prevention of glomerular and proximal tubular superoxide anion production induced by NADPH oxidase activity.

Curcumin inhibits the development of non‑small cell lung cancer by inhibiting autophagy and apoptosis

“…Previous studies have demonstrated that curcumin suppresses cytotoxicity and DNA injury by suppressing oxidative damage caused by reactive oxygen species (27,28). The current study observed that curcumin decreased the viability of human lung cancer cells in an apparent dose-and time-dependent manner.…”

Curcumin prevents mitochondrial dynamics disturbances in early 5/6 nephrectomy: Relation to oxidative stress and mitochondrial bioenergetics

“…On the other hand, curcumin is the main active compound of Curcuma longa L. and is considered a bifunctional antioxidant, its consumption, in both animals and humans, has been recognized as safe by the Food and Drug Administration . Curcumin is an effective ROS scavenger; it is able to scavenge superoxide anion ( ), singlet oxygen, hydrogen peroxide (H 2 O 2 ), peroxynitrite anion, hypochlorous acid, hydroxyl radicals, and peroxyl radicals . Curcumin has been reported to prevent oxidative stress and renal damage induced by chemicals like gentamicin , cisplatin and maleate .…”

Recent Advances of Curcumin in the Prevention and Treatment of Renal Fibrosis

“…In our group we also found that curcumin could inhibit the occurrence of EMT in renal tubular epithelial cells via regulating several sites of the TGF- β /Smads signal transduction pathway in UUO rats [49]. The inhibitory effect of curcumin on EMT was also demonstrated in cisplatin-induced renal fibrosis rats [31]. …”

“…The protective effect of curcumin was more obvious in pretreatment group (administration of curcumin before selenium, 24 h) than simultaneous or posttreatment group (administration of curcumin after selenium treatment, 24 h). In rats with contrast-induced nephropathy [30], 5/6 Nx [24], and cisplatin-induced nephrotoxicity [31], curcumin treatment (60 and 120 mg/kg for 60 days [24]) increased antioxidant profiles (e.g., superoxide dismutase (SOD), enzymes catalase, glutathione reductase, glutathione peroxidase, and glutathione) and decreased oxidant profile (malondialdehyde) in the kidneys. Further, curcumin may exhibit renoprotective effect through Nrf2 translocation [31, 53], which beneficially contributes to ameliorating cisplatin-induced loss of tight junction proteins (claudin-2 and occludin) and adherens junction protein (E-cadherin and β -catenin) [31].…”

“…In rats with contrast-induced nephropathy [30], 5/6 Nx [24], and cisplatin-induced nephrotoxicity [31], curcumin treatment (60 and 120 mg/kg for 60 days [24]) increased antioxidant profiles (e.g., superoxide dismutase (SOD), enzymes catalase, glutathione reductase, glutathione peroxidase, and glutathione) and decreased oxidant profile (malondialdehyde) in the kidneys. Further, curcumin may exhibit renoprotective effect through Nrf2 translocation [31, 53], which beneficially contributes to ameliorating cisplatin-induced loss of tight junction proteins (claudin-2 and occludin) and adherens junction protein (E-cadherin and β -catenin) [31]. It is demonstrated that Nrf2 exerted cytoprotective effect through binding to antioxidant response elements [54, 55] (Figure 2).…”