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. 2020 Oct 20;18:400. doi: 10.1186/s12967-020-02574-8

Table 2.

Roles of oxidative stress in pathogenesis of contrast-induced nephropathy: reports from in vivo studies

Animals Models Major findings Interpretations References
Renal function Oxidative stress Inflammatory markers Apoptosis Histopathology
Male BALB/c mice Restricted water 24 h treated with iodixanol/IV/24 h

↑ Cr

↑ BUN

↑ urinary NAG

↓ RBF

↑ ROS

↑ 8-OHdG-positive cells

↓ SOD-1

↔ SOD-2

↑ phospho- NF-kB p65

↑ TNF-α

↑ IL-6

↑ iNOS-positive cells

↑ ROCK-2 protein

↑ p-MYPT1 and p-MYPT1/MYPT ratio

↑ TUNEL-positive cells

↑ cleaved caspase-3

↑ Bax

↓ p-Akt/total Akt ratio

Moderate tubular injury with tubular degeneration

Loss of brush border membranes

Formation of cast

Vacuolization of tubular epithelial cells

Dilation of tubules

Iodixanol increased ROCK-2 activity, contributing to increased NF-kB transcriptional activity, oxidative stress, inflammation and apoptosis, leading to impaired renal function [23]
Male C57BL/6 J mice L-NAME/IP + indomethacin/IP treated with iohexol/IP/1 h ↑ Cr

↓ SIRT1

↑↑ PGC-1α expression

↑ phosphor-Ser256 FoxO1 expression

↓ SOD2

↑ MDA

↑ TUNEL-positive cells

↑ cleaved caspase-3

Tubular vacuolization

Disruption of tubular structures in outer medulla

↑ macrophage infiltration

Iohexol upregulated SIRT1-PGC-1α-FoxO1 signaling mediated oxidative stress, apoptosis, leading to impaired renal function [21]
Male Sprague–Dawley rats Dehydration 48 h treated with iohexol/IV/24 h

↑ Cr

↑ BUN

↑ 8-OHdG-positive cells

↑ MDA

↑ TUNEL-positive cells

↑ Nrf-2-positive cells

↑ p-Akt/Akt

↑ nuclear-Nrf-2

↑ HO-1/Actin

Severe tubular detachment

Foamy degeneration of tubular cells

CM upregulated PI3K/Akt/Nrf-2 pathway, leading to increased oxidative stress and apoptosis, leading to impaired renal function [26]
Adult Sprague Dawley rats Indomethacin/IV + L-NAME/IV treated with ioversol/IV/72 h

↑ Cr

↑ BUN

↑ MDA

↓ SOD

↑ Nrf-2/HO-1-positive cells

↑ HO-1-positive cells

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

↑ Nrf-2 nuclear translocation

↑ HO-1 and NQO-1 protein levels

Tubular necrosis

Hemorrhagic casts

Nrf-2/HO-1 pathway regulated adaptive cytoprotective responses to counteract tissue damage, oxidative stress and apoptosis caused by CM [27]
Male Sabra rats (Wistar-derived colony) Low sodium diet 7 d + indomethacin/IV treated with iothalamate/IV

↑ Cr

↓ CrCl

↑ O2 production

↓ eNOS

↑ iNOS

↑ HO-1 protein

↑ renal heme

↑ caspase-3

↑ caspase-9

↑ Bax

↓ Bcl-2

Increased level of HO-1 are protective against AKI due to CM exposure [28]
Male C57BL/6 mice Water deprivation 16 h + indomethacin/IP + L-NAME/IP treated with iohexol/24 h

↑ BUN

↔ Cr

↑ KIM-1-positive cells

↔ SOD

↔ Nox4

↔ Nox1

↑ Nox2

↑ 8-OHdG-positive cells

↑ phospho-p38/p38

↑ phospho-pJNK/pJNK

↑ phospho-ERK/ERK

↑ Bax

↓ Bcl-2

↑ TUNEL-positive cells

Tubular epithelial cell shedding

Basement membrane nudity

Vacuolar degeneration of tubular epithelial cells

Protein casts

Tubular dilation

Loss of tubular brush borders

Necrosis of partial tubular epithelial cells

↑ tubular pathological scores

The Nox4/Nox2 axis was involved in the amplification of ROS production, apoptosis and CIN progression, leading to impaired renal function [17]
Male Wistar rats Diatrizoate/no dose provided/IV/1, 24 h ↑ TUNEL-positive cells Diatrizoate caused apoptosis, leading to impaired renal function [19]

AKI, acute kidney injury; Bax, Bcl2-associated X protein; Bcl-2, B-cell lymphoma 2; CAG, coronary angiography; CIN, contrast-induced nephropathy; CM, contrast media; Cr, creatinine; CrCl, creatinine clearance; DNA, deoxyribonucleic acid; eNOS, endothelial nitric oxide; HO-1, heme oxygenase 1; iNOS, inducible nitric oxide synthase; KIM-1, kidney injury molecule-1; L-NAME, Nω-nitro-L-arginine methyl ester; MDA, malondialdehyde; MESNA, sodium-2-mercaptoethane sulphonate; NADPH, nicotinamide adenine dinucleotide phosphate; NF-kB, nuclear factor-kB; NO, nitric oxide; Nox4, NADPH oxidases; NQO-1, NAD(P)H: quinone oxidoreductase 1; Nrf-2, nuclear factor erythroid 2-related factor 2; ROS, reactive oxygen species; TUNEL, terminal deoxynucleotide transferase dUTP nick end labeling; 8-OHdG, 8-hydroxy-2′-deoxyguanosine