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Table 3 Interventions to attenuate oxidative stress in contrast-induced nephropathy: reports from in vitro studies

From: Contrast-induced nephropathy and oxidative stress: mechanistic insights for better interventional approaches

Models

Methods (drug/dose/route/duration)

Major findings

Interpretations

References

Oxidative stress

Apoptosis

Histopathology

HK-2 cells treated with iohexol/200 mg I/mL/6 h

Atorvastatin/1, 20, 40 µM/2 h prior to iohexol

–

↑ MTT cell viability

↓ annexin V-positive cells

↓ mRNA expression of intracellular NOX4 and p22phox

All effects by atorvastatin 40 µM

↓ nuclear fragmentation

↓ organelle reduction

↓ mitochondrial vacuolar degeneration

Atorvastatin attenuated iohexol-induced cytotoxicity through downregulation of NOX4 and p22phox

[16]

MDCK cells & HK-2 cells treated with iodixanol/200 mg/mL/3 h

Atorvastatin/0.2 µmol/L/12 h prior to iodixanol

–

↑ MTS cell viability

↓ caspase-3

↓ JNK

↓ p53 phosphorylation

–

Pretreatment with atorvastatin reduced contrast-induced JNK activation, leading to apoptosis

[29]

HK-2 cells treated with iohexol 150 mg I/mL/12 h

Specific Nox1/4 inhibitor (GKT137831)/20 µg/mL/30 min prior to iohexol

↑ Nox2 and Nox4 mRNA expression

↓ ROS production

↓ caspase 3/7 activity

↑ MTT and ATPlite cell viability

↓ MAPK pathways (phospho-p38, JNK and ERK pathways)

↓ Bax

–

Inhibition of Nox4 activity attenuated CIN

[17]

NRK-52E rodent tubular cells treated with iohexol/100 mg/mL/3 h

Resveratrol/10, 50 µmol/24 h prior to iohexol

↑ SIRT1

↑ PGC-1α expression

↑ SOD2

↑ MTT cell viability

–

Resveratrol attenuated iohexol-induced nephrotoxicity via activating SIRT1-PGC-1α-FoxO1 signaling, leading to reduced oxidative stress and apoptosis

[21]

HK-2 cells treated with ioversol/50 mg/mL/24 h

Sulforaphane (Nrf-2 activator)/5 µmol/L/30 min prior to ioversol

↓ ROS production

↑ MTT cell viability

↑ Nrf-2, NQO-1 and HO-1 gene expression

↔ MTT cell viability in Nrf-2 siRNA

–

Renoprotective effect of sulforaphane in ioversol-induced nephrotoxicity was associated with Nrf-2/HO-1 pathway

[27]

HK-2 cells treated with H2O2/250 µM/L/3, 24 h

HSA-Trx/0.1, 0.5, 1, 5, 10 µmol/L/1 h prior to H2O2

↓ ROS production in a dose-dependent manner

↓ WST-8-positive cells in a dose-dependent manner

–

HSA-Trx attenuated oxidative stress and inflammation in CIN

[37]

HK-2 cells treated with H2O2/500 µmol/L/24 h

Magnolin/10, 40 µg/mL/prior to H2O2

↓ ROS

↓ caspase-3

↑ Bcl-2

–

Magnolin attenuated oxidative stress and apoptosis

[49]

HK-2 cells treated with H2O2/250 mM/3, 24 h

Salvianolic acid B/50 µM/1 h prior to H2O2

Wortmannin (PI3K inhibitor)/10 µM/1 h prior to H2O2

↓ ROS production

↑ MTT cell viability

↑ CCK-8 cell viability

↑ p-Akt and nuclear-Nrf-2 expression (salvianolic acid B)

↓ p-Akt and nuclear-Nrf-2 expression (wortmannin)

–

Salvianolic acid B attenuated oxidative stress and provided cell protection via PI3K/Akt/Nrf-2 pathway

[26]

  1. ATF2, activating transcriptional factor 2; Bax, Bcl2-associated X protein; Bcl-2, B-cell lymphoma 2; CIN, contrast-induced nephropathy; ERK, extracellular signal-regulated kinase; GPx, glutathione peroxidase; GSH, glutathione; GSSG, glutathione disulfide; HK-2 cells, human embryonic proximal tubular epithelial cells; HO-1, heme oxygenase 1; HSA-Trx, recombinant human serum albumin-Thioredoxin-1 fusion protein; IV, intravenously; JNK, c-Jun N-terminal kinase; LDH, lactate dehydrogenase; MAPKs, mitogen-activated protein kinases; MDCK cells, Madin Darby distal nonhuman tubular epithelial cells; MESNA, sodium-2-mercaptoethane sulphonate; MTS, 5-(3-carboxymethoxyphenyl)-2H-tetrazolium inner salt; MTT, 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide; NADPH, nicotinamide adenine dinucleotide phosphate; Nox4, NADPH oxidases; NQO-1, NAD(P)H: quinone oxidoreductase 1; Nrf-2, nuclear factor erythroid 2-related factor 2; p22phox, p22 phagocyte B-cytochrome; PGC-1α, peroxisome proliferator-activated receptor-γ co-activator 1α; ROS, reactive oxygen species; siRNA, short interfering ribonucleic acid; SIRT1, sirtuin 1; SOD, superoxide dismutase