Table 2.
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