Curcumin prevents maleate-induced nephrotoxicity: Relation to hemodynamic alterations, oxidative stress, mitochondrial oxygen consumption and activity of respiratory complex I

Abstract

The potential protective effect of the dietary antioxidant curcumin (120 mg/Kg/day for 6 days) against the renal injury induced by maleate was evaluated. Tubular proteinuria and oxidative stress were induced by a single injection of maleate (400 mg/kg) in rats. Maleate-induced renal injury included increase in renal vascular resistance and in the urinary excretion of total protein, glucose, sodium, neutrophil gelatinase-associated lipocalin (NGAL) and N-acetyl β-D-glucosaminidase (NAG), upregulation of kidney injury molecule (KIM)-1, decrease in renal blood flow and claudin-2 expression besides of necrosis and apoptosis of tubular cells on 24 h. Oxidative stress was determined by measuring the oxidation of lipids and proteins and diminution in renal Nrf2 levels. Studies were also conducted in renal epithelial LLC-PK1 cells and in mitochondria isolated from kidneys of all the experimental groups. Maleate induced cell damage and reactive oxygen species (ROS) production in LLC-PK1 cells in culture. In addition, maleate treatment reduced oxygen consumption in ADP-stimulated mitochondria and diminished respiratory control index when using malate/glutamate as substrate. The activities of both complex I and aconitase were also diminished. All the above-described alterations were prevented by curcumin. It is concluded that curcumin is able to attenuate in vivo maleate-induced nephropathy and in vitro cell damage. The in vivo protection was associated to the prevention of oxidative stress and preservation of mitochondrial oxygen consumption and activity of respiratory complex I, and the in vitro protection was associated to the prevention of ROS production.

The nephroprotection exerted by curcumin in maleate‐induced renal damage is associated with decreased mitochondrial fission and autophagy

“…Mitochondria are a source of ROS production under physiological and pathological conditions . As described above, maleate induces mitochondrial O 2 • — production, which agrees with previous findings showing that mitochondrial respiration is also altered by maleate in proximal tubules . These findings encouraged us to explore the effect of maleate on mitochondrial dynamics in the kidney.…”

“…F–I) that is ubiquitously expressed in all epithelia, in maleate and curcumin‐treated rats. We previously reported that curcumin prevented maleate‐induced loss of claudin‐2 evaluated by WB . In this study we additionally explore the localization of claudin‐2 (Figs.…”

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

“…However, its use is limited by its serious side effects such as nephrotoxicity, with proximal tubular epithelial cells as the primary target 52 nephrotoxicity 22,33 . Interestingly, this has been observed in another model of renal damage induced by maleate 61 . It was found that curcumin-treated rats showed minor characteristic alterations in renal tissue after acute injury induced by CIS, such lesser cell detaching, apoptosis, tubular necrosis and cast formation in the tubular lumen ( Figure 4C; Table 2).…”

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

“…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 . In 5/6NX model, curcumin administration reverts proteinuria, glomerular and systemic hypertension, glomerular hyperfiltration, glomerular sclerosis, interstitial fibrosis, and inflammation , thus preventing the loss of renal function.…”