Table 4.

Interventions to attenuate oxidative stress in contrast-induced nephropathy: reports from in vivo studies

Animals	Models	Intervention (drug/dose/route/duration)	Major findings					Inter-pretations	References
			Renal function	Oxidative stress	Inflammatory markers	Apoptosis	Histo-pathology
Streptozotocin-induced diabetes in male Wistar rats	Indomethacin/IV + L-NAME/IV + amidotriazoate meglumine	Rosuvastatin/10 mg/kg/day/po/OD/5 day prior to amidotriazoate meglumine	↓ Cr ↑ CrCl ↓ urine microprotein	↓ kidney TBARS ↓ serum MDA ↓ serum PCC ↑ serum thiol	↑ kidney nitrite ↓ IL-6 ↓ TNF-α	↓ TUNEL-positive cells ↓ expression of phospho-p38 ↓ cleaved caspase-3 ↓ Bax/Bcl-2 ratio	↓ histological scores	Rosuvastatin attenuated CIN by modulation of NO, inflammatory responses, oxidative stress and apoptotic processes, leading to improved renal function	[30]
Adult Sprague Dawley rats	Water deprivation 24 h treated with 25% glycerol/IM + iohexol	Simvastatin/15, 30, 60 mg/kg/po/24 h prior to iohexol/4 d	↓ Cr in a dose-dependent manner ↓ BUN in a dose-dependent manner	↓ kidney TBARS ↑ GSH	↓ MPO ↑ NO	–	↓ tubular dilatation, tubular vacuolation, and tubular necrosis in a dose dependent manner	Simvastatin prevented CIN and structural changes in kidney via a reduction of oxidative stress and inflammation, leading to improved renal function	[32]
Male Sprague–Dawley rats	Water deprivation 72 h + furosemide 10 mg/kg/IM treated with iohexol	Rosuvastatin/10 mg/kg/day/po/OD/3 day before and 4 h after iohexol Simvastatin/80 mg/kg/day/po/OD/3 day before and 4 h after iohexol Atorvastatin/20 mg/kg/day/po/OD/3 day before and 4 h after iohexol	↓ Cr by atorvastatin and rosuvastatin	↓ kidney TBARS ↓ serum MDA ↑ serum thiol	↓ IL-6 ↓ MCP-1 ↓ TNF-α Most effective in rosuvastatin > atorvastatin ↑ NO by atorvastatin	↓ TUNEL-positive cells ↓ Bax/Bcl-2 ratio Most effective in atorvastatin > rosuvastatin	↓ tubular necrosis and medullary congestion by atorvastatin and rosuvastatin	Atorvastatin and rosuvastatin prevented CIN and reduced oxidative stress In addition, atorvastatin was most effective in attenuating NO system dysfunction and cell apoptosis, whereas rosuvastatin was most effective in reduction of inflammation, leading to improved renal function	[31]
Male Sprague–Dawley rats	Dehydration 3 day treated with furosemide/IM + iohexol/IV	Xuezhikang/2,400 mg/kg/day/po/3 day prior to iohexol Atorvastatin/20 mg/kg/day/po/3 day prior to iohexol	↓ Cr ↓ BUN	↓ renal MDA ↑ GSH	↓ TNF-α ↓ IL-6 ↑ kidney total NO (nitrite/nitrate)	↓ TUNEL-positive cells ↑ Bcl-2/Bax ratio by xuezhikang	↓ tubular necrosis and medullary congestion ↓ medullary damage scores	Xuezhikang and atorvastatin shared similar effect on iohexol-induced CIN, leading to improved renal function	[33]
Female albino Wistar rats	Water deprivation 24 h + 25% glycerol/IM treated with iohexol/IV	Agomelatine/20, 40 mg/kg/po/OD/24 h before and 4 day after iohexol	↓ Cr ↓ BUN	↑ SOD ↑ GSH ↓ MDA	↓ TNF-α ↓ NF-kB ↓ IL-6 mRNA expression	–	↓ hyaline and hemorrhagic casts & tubular necrosis	Agomelatine provided nephroprotective, antioxidant and anti-inflammatory effects against CIN in rats, leading to improved renal function	[42]
Adult male Sprague–Dawley rats	Dehydration 24 h + furosemide/IM + indomethacin/IP treated with iomeprol	Melatonin/10 mg/kg/IP/15 min prior to ± 24 h after iomeprol	↓ Cr ↑ CrCl ↓ FENa All effects by pre- and post-treatment	–	–	–	–	Melatonin prevented and attenuated CIN in rats with pre- & post-treatment, leading to improved renal function	[43]
Male Sprague–Dawley rats	Streptozotocin-induced diabetes treated with iohexol/IV	Melatonin/20 mg/kg/day/IP/OD/7 day prior to iohexol	↓ Cr	↓ MDA ↑ SOD ↑ GSH ↓ CAT	↓ MPO ↓ IL-6 ↓ IL-33	–	↓ apoptosis ↓ necrotic changes ↓ glucogenic vacuolization ↓ inflammatory cell infiltration	Melatonin provides functional and histologic protection against CIN via inhibiting of IL-33, leading to improved renal function	[44]
Male Sprague–Dawley rats	Indomethacin/IV + L-NAME/IV treated with ioversol/IV	HSA-Trx/30 mg/kg/IV/1 h prior to ioversol	↓ Cr ↓ BUN ↓ urinary NAG ↑ CrCl	↓ 8-OHdG-positive cells ↓ MDA	–	↓ TUNEL-positive cells	↓ renal tubular injuries	Administration of single dose of HSA-Trx before induction of CIN exerted renoprotective effects in CIN rat model, leading to improved renal function	[37]
Adult male Sprague Dawley rats	Indomethacin/IV + L-NAME/IV treated with iopromide/IV	Vitamin E/250, 500 mg/kg/day/po/5 day prior to iopromide	↓ Cr	↓ MDA ↑ TAC ↑ SOD in a dose-dependent manner	–	–	↓ severity of proximal tubular epithelial cells necrosis and proteinaceous cast ↓ peritubular capillary congestion ↓ interstitial edema	Vitamin E prevented CIN through its antioxidant activity, leading to improved renal function	[35]
Male Sprague–Dawley rats	Indomethacin 10 mg/kg + L-NAME + ioversol/IV	Antithrombin III/500 µg/kg/IV/30 min before or after ioversol	↓ Cr ↓ BUN ↑ renal cortical blood supply ↓ intrarenal resistance index	↓ MDA ↑ SOD	↓ TNF-α ↓ MCP-1 ↓ ICAM-1 expression ↓ F4/80-positive cells infiltration	↓ cleaved caspase-3 expression ↑ Bcl-2	↓ renal tubular detachment ↓ brush border loss ↓ necrosis of tubular cells	Antithrombin III prevented and attenuated CIN through inhibiting inflammation, oxidative stress, apoptosis and improving RBF, leading to improved renal function	[53]
Male Sprague–Dawley rats	Dehydration 72 h treated with iopamidol/IV	Astragaloside IV/20 mg/kg/po/OD/7 day prior to iopamidol	↓ Cr ↓ BUN ↓ cystatin C ↓ NGAL ↓ uKIM-1	↓ MDA ↑ CAT ↑ SOD ↓ serum, urinary and renal 8-OHdG	–	↓ TUNEL-positive cells ↓ caspase-3 activity ↓ cleaved caspase-3 protein expression ↓ Bax protein and mRNA expressions ↑ Bcl-2 protein and mRNA expressions ↓ p38 MAPK phosphorylation	↓ tubular injuries	Astragaloside IV prevented AKI through inhibition of oxidative stress and apoptosis pathways, leading to improved renal function	[45]
Male Wistar rats	Gentamicin/IP/6 day treated with gastrographin/IV	Cardiotrophin-1/100 µg/kg/day/IV/24 h prior to and 4 day after gastrographin	↓ Cr ↓ BUN ↑ CrCl ↑ inulin clearance ↑ RBF ↓ RVR ↓ proteinuria ↓ albuminuria ↓ NAG ↓ uKIM-1 ↓ PAI-1	↓ MDA	–	↓ cleaved caspase-3-positive cells	↓ tubular necrosis in cortex ↓ tubular obstruction with hyaline material in medulla ↓ Ki-67-positive proliferating cells	Cardiotrophin-1 prevented CIN through a reduction of oxidative stress, leading to improved renal function	[54]
Male albino Wistar rats	Water deprivation 24 h + 25% glycerol/IM treated with iohexol/IV	L-carnitine/200, 400 mg/kg/IP/24 h prior to iohexol	↓ Cr ↓ BUN	↑ SOD ↑ GSH ↓ MDA by L-carnitine 400 mg/kg	↓ TNF-α ↓ TGF-1β expression ↓ IL-1β mRNA expression ↓ TNF-α and NF-kB-positive cells	↓ caspase-3 mRNA expression	↓ hyaline and hemorrhagic casts ↓ tubular necrosis in cortical segments of proximal tubules	L-carnitine protected against CIN via a reduction of oxidative stress, inflammation and apoptosis in rats, leading to improved renal function	[36]
Male Wistar-albino rats	Dehydration 24 h + furosemide/IM + indomethacin/IP treated with iomeprol/IV	Curcumin/200 mg/kg/day/po/5 day prior to & 5 day after iomeprol	↓ Cr ↓ BUN	↑ SOD ↑ CAT ↑ GSH ↑ GSH-Px ↓ MDA	↓ iNOS-specific-positive cells	↓ LC3/B-specific-positive cells ↓ cleaved caspase 3-specific-positive cells	↓ necrotic and degenerative changes ↓ intertubular hemorrhage	Curcumin attenuated inflammation and apoptosis in CIN, leading to improved renal function	[46]
Male BALB/c mice	Restrict water 24 h treated with iodixanol/IV	Fasudil/3, 10 mg/kg/IV/12, 2 h prior to and 4 h after iodixanol	↓ Cr ↓ BUN ↓ urinary NAG ↑ RBF ↑ renal vasodilation All effects by 10 mg/kg	↓ ROS in a dose-dependent manner ↓ 8-OHdG-positive cells in a dose-dependent manner ↑ SOD-1 ↔ SOD-2	↓ phospho-NF-kB p65 ↓ IL-6 ↓ TNF-α ↓ iNOS-positive cells (10 mg/kg)	↓ ROCK-2 protein ↓ p-MYPT1 and p-MYPT1/MYPT1 ratio ↓ TUNEL-positive cells ↓ cleaved caspase-3 ↓ Bax ↑ Bcl-2 ↑ p-Akt/total Akt ratio All effects by 10 mg/kg	↓ tubular injury ↓ formation of cast All effects by 10 mg/kg	Fasudil exerted renoprotective effects by suppressing inflammation, apoptosis and oxidative stress via inhibiting Rho/ROCK pathway and ameliorating hemodynamic disturbances, leading to improved renal function	[23]
Streptozotocin-induced diabetes in male Sprague–Dawley rats	Treated with diatrizoate meglumine/IV	Exendin-4/25 nmol/kg/SC/10 day prior to diatrizoate/11 d	↓ Cr ↓ BUN ↓ urinary albumin excretion ↑ CrCl	↓ MDA ↓ ET-1 ↑ GSH ↑ SOD	↑ nitrate ↑ eNOS	↓ caspase-3 expression	↓ edema ↓ tubular vacuolization ↓ hemorrhage	Pretreatment with exendin-4 ameliorated CIN effects independent of glycemic state, leading to improved renal function	[55]
Female Sprague–Dawley rats	Water deprivation 24 h + diatrizoate/IV	Grape seed proanthocyanidin/100 mg/kg (1 cm3)/po/6 day prior to diatrizoate/5 d	↓ Cr ↓ BUN	↓ MDA ↓ TOS ↓ OSI	–	↓ TUNEL-positive cells	↓ perivascular edema ↓ vascular congestion ↓ tubular vacuoles ↓ renal injury score	Proanthocyanidin attenuated CIN by reducing oxidative damage and apoptosis, leading to improved renal function	[47]
Male Wistar albino rats	24-h dehydration + furosemide/IM + indomethacin/IP treated with iomeprol/IV	Lycopene/4 mg/kg/day/po/5 day prior to and 5 day after iomeprol	↓ Cr ↓ BUN	↑ SOD ↑ CAT ↑ GSH ↑ GSH-Px ↓ MDA	↓ iNOS-specific-positive cells	↓ LC3/B-specific positive cells ↓ cleaved caspase 3-specific positive cells	↓ number of infiltrated inflammatory cells and necrotic degenerative changes	Lycopene prevented and attenuated inflammation, autophagy and apoptosis in CIN rats, leading to improved renal function	[48]
Male Sprague–Dawley rats	Indomethacin/IV + L-NAME treated with ioversol/IV	Magnolin/1 mg/kg/SC/15 min prior to ioversol	↓ Cr ↓ BUN ↓ serum NGAL ↓ uKIM-1	↓ MDA ↑ SOD	–	↓ TUNEL-positive cells ↓ caspase-3 activity ↑ Bcl-2 expression	↓ renal tubular injury scores	Magnolin attenuated CIN in rats through reducing oxidative stress and apoptosis, leading to improved renal function	[49]
Male Sprague–Dawley rats	Deprived of water 3 d + indomethacin/IV treated with diatrizoate	Recombinant manganese SOD/15 µg/kg/IP/4 h prior to diatrizoate	↑ GFR	↑ SOD ↓ intrarenal superoxide anion (O2−) ↓ ROS production	–	–	↓ tubular necrosis ↓ proteinaceous casts	Recombinant manganese SOD reduced oxidative stress, thus preventing CIN, leading to improved renal function	[41]
Adult male Wistar rats	Meglumine ioxaglate/IV	NAC/150 mg/kg/day/IP/6 h before and 6 h after ioxaglate Ozone (5%O3 – 95%O2)/1 mg/kg/IP/6 h prior to and 6 h after or 5 day after ioxaglate	↓ Cr (NAC) ↓ NGAL	↑ TAC by ozone ↓ PCC	–	–	↓ renal tubular injury ↓ hemorrhage	NAC and ozone treatment prevented and attenuated CIN via a reduction of oxidative stress, leading to improved renal function	[39]
Wistar albino rats	Water deprivation 72 h treated with diatrizoate meglumine/IV	Nebivolol/2 mg/kg/day/po/3 day prior to and 2 day after diatrizoate	↔ Cr ↔ CrCl ↔ BUN ↓ urine microprotein	↓ serum PCC ↓ kidney TBARS ↓ MDA ↑ serum thiol	↑ kidney nitrite levels	–	↓ tubular necrosis ↓ proteinaceous casts ↔ medullary congestion	Nebivolol attenuated either systemic or renal oxidative stress and increased either nitrite production or restored pathology, leading to improved renal function	[56]
Male Wistar albino rats	Indomethacin/IV + L-NAME/IV treated with amidotrizoate meglumine/IV	Paricalcitol/0.4 µg/kg/day/IP/3 day prior to and 2 day after amidotrizoate	↓ Cr ↑ CrCl ↓ FENa	↓ MDA ↓ kidney TBARSs	↓ VEGF score	–	↓ tubular necrosis ↓ proteinaceous casts ↓ medullary congestion	Paricalcitol reduced unfavourable histopathology of CIN via antioxidant effects, leading to improved renal function	[38]
Male Sprague Dawley rats	Indomethacin/IV + L-NAME/IV treated with iopromide/IV	Phyllanthus emblica extract/125, 250, 500 mg/kg/day/po/5 day prior to iopromide	↓ Cr (250, 500 mg/kg/d) ↓ BUN	↓ MDA (250, 500 mg/kg/d) ↑ TAC (250, 500 mg/kg/d) ↑ SOD ↑ CAT	–	–	↓ tubular necrosis ↓ proteinaceous cast formation ↓ peritubular capillary congestion ↓ interstitial edema All changes by 250, 500 mg/kg/d	Phyllanthus emblica extract exerted renoprotective effects of CIN in rat, leading to improved renal function	[50]
Streptozotocin-induced diabetes in male Sprague–Dawley rats	Treated with diatrizoate/IV	5% Probucol/500 mg/kg/po/14 day prior to diatrizoate	↓ Cr ↑ CrCl	–	–	↑ p-ERK1/2 ↓ p-JNK ↑ Bcl-2 ↓ Bax ↓ caspase-3	↓ vacuolar degeneration of renal tubular cells ↑ dilatation of lumen ↓ renal tubular injury score	Probucol exerted protective effects on CIN in diabetic rats via inhibition of renal cell apoptosis, leading to improved renal function	[34]
Male Sprague–Dawley rats	Iohexol/IP	Rapamycin/2, 5 mg/kg/IP/7 day prior to iohexol	↓ Cr in a dose-dependent manner	↓ MDA in a dose-dependent manner ↓ CAT in a dose-dependent manner	–	↑ LC3II/I ↑ Beclin-1 ↑ Pink1 ↓ P62 ↑ ∆ψm in a dose-dependent manner ↓ cytosolic/mitochondrial Cyt c in a dose-dependent manner ↑ TOMM20-stained mitochondria in a dose-dependent manner ↑ LC3-stained autophagosomes ↑ LAMP2-stained lysosomes ↓ renal tubular epithelial cell apoptosis in a dose-dependent manner	↓ renal tubular necrosis in a dose-dependent manner	Rapamycin exerted renoprotective effects against CIN via suppressing mitochondrial injury and oxidative stress, mitophagy and apoptosis, leading to improved renal function	[62]
Male C57BL/6 J mice	L-NAME/IP + indomethacin/IP treated with iohexol/IP	Resveratrol/30 mg/kg/IP/simultaneously with iohexol	↓ Cr	↑ SIRT1 ↑ PGC-1α expression ↓ phosphor-Ser256 FoxO1 expression ↑ SOD2 ↓ MDA	–	↓ TUNEL-positive cells ↓ cleaved caspase-3	↓ severity score for tubular vacuolization ↓ disruption of tubular structures ↓ macrophage infiltration	Resveratrol attenuated CIN via a reduction of oxidative stress and apoptosis, leading to improved renal function	[21]
Wistar rats	Indomethacin/IV + L-NAME/IV treated with diatrizoate meglumine/IV	NAC/100 mg/kg/po/7 day prior to diatrizoate Salidroside/20 mg/kg/IP/7 day prior to diatrizoate	↓ Cr ↓ BUN ↓ NAG ↓ 24-h urinary protein	↑ SOD ↓ MDA ↓ angiotensin II ↓ 8-OHdG	↑ NO ↑ eNOS mRNA and protein ↑ NOS activity	–	↓ disintegrated and shed brush border of tubular epithelial cells ↓ vacuolar degeneration ↓ cell debris and protein cast in tubular lumen ↓ focal interstitial edema and inflammatory cell infiltration	Salidroside or NAC prevented CIN via a reduction of oxidative stress, leading to improved renal function	[40]
Male Sprague–Dawley rats	Dehydration 48 h treated with iohexol/IV	Salvianolic acid B/50 mg/kg/IV/5 min prior to iohexol Wortmannin (PI3K inhibitor)/15 µg/kg/IV/5 min prior to iohexol Sulforaphane (Nrf-2 activator)/10 mg/kg/IV/5 min prior to iohexol	↓ Cr (salvianolic acid and sulforaphane) ↓ BUN (salvianolic acid) ↑ Cr (wortmannin)	↓ 8-OHdG-positive cells (salvianolic acid and sulforaphane) ↔ 8-OHdG-positive cells (wortmannin) ↓ MDA (salvianolic acid and sulforaphane) ↔ MDA (wortmannin)	–	↓ TUNEL-positive cells (salvianolic acid and sulforaphane) ↑ TUNEL-positive cells (wortmannin) ↑ Nrf-2-positive cells (salvianolic acid and sulforaphane) ↔ Nrf-2-positive cells (wortmannin) ↑ p-Akt/Akt (salvianolic acid) ↔ p-Akt/Akt (sulforaphane) ↓ p-Akt/Akt (wortmannin) ↑ Nrf-2/Histone H3 (salvianolic acid and sulforaphane) ↓ Nrf-2/Histone H3 (wortmannin) ↑ HO-1/Actin (salvianolic acid and sulforaphane) ↓ HO-1/Actin (wortmannin)	↓ histological scores (tubular epithelium degeneration) (salvianolic acid B and sulforaphane) ↑ histological scores (wortmannin)	Salvianolic acid B exerted renoprotection and antioxidative effects through PI3K/Akt/Nrf2 pathway, leading to improved renal function	[26]
Male Sprague–Dawley rats	Gentamicin/SC + iothalamate meglumine/IV	Sesame oil/0.5 ml/kg/po/1 h prior to iothalamate	↓ Cr ↓ BUN	↓ MDA ↓ renal hydroxyl radicals ↓ renal superoxide anion generation	↓ MPO ↓ renal nitrite/nitrate level ↓ iNOS expression	–	↓ inflammatory cell infiltration ↓ tubular dilation ↓ congestion in tubules	Sesame oil prevented CIN via inhibiting oxidative stress in rats, leading to improved renal function	[51]
Male Wistar rats	24-h water deprivation + L-NAME/IP + indomethacin/IP treated with iohexol/IV	Sildenafil citrate/50 mg/kg/day/po/5 day prior to and 2 day after iohexol	↓ Cr ↑ GFR ↑ RPF ↑ RBF ↓ RVR ↓ BUN ↓ proteinuria	↓ intracellular O2− ↓ H2O2	–	–	–	Sildenafil prevented CIN through vasodilator and antioxidant activity, leading to improved renal function	[58]
Male Wistar rats	12-h dehydration + L-NAME/IP + indomethacin/IP treated with iopromide/IV	Sildenafil/10 mg/kg/day/po/7 day prior to iopromide Taladafil/5 mg/kg/day/po/7 day prior to iopromide NAC/100 mg/kg/day/po/7 day prior to iopromide	↓ Cr ↓ BUN	–	–	–	↓ hydropic changes of renal tubules ↓ Bowman space with lobulated glomerulus ↓ alteration of macula densa	Sildenafil and taladafil prevented CIN-related structural kidney damage and superior to NAC	[59]
Male Wistar rats	12-h dehydration + L-NAME/IP + indomethacin/IP treated with iopromide/IV	Sildenafil/10 mg/kg/day/po/7 day prior to iopromide Taladafil/5 mg/kg/day/po/7 day prior to iopromide NAC/100 mg/kg/day/po/7 day prior to iopromide	↓ Cr ↓ BUN	↑ TAC ↑ GSH ↑ CAT ↓ PCC ↓ TBARS	–	–	–	Sildenafil and taladafil prevented CIN through antioxidant activity	[60]
Adult male Swiss mice	Overnight water deprivation + L-NAME/IP + indomethacin/IP treated with ioversol/IP	NAC/200 mg/kg/po/5 day prior to ioversol Silymarin/50, 200, 300 mg/kg/po/5 day prior to ioversol	↓ Cr in a dose-dependent manner (silymarin) ↓ BUN in a dose-dependent manner ( silymarin) ↓ cystatin C in a dose-dependent manner (silymarin)	↓ intracellular superoxide (O2−) ↓ H2O2 ↓ OH−/ONOO− ↓ advanced oxidation protein products in plasma (silymarin 300 mg)	–	↓ DNA damage (silymarin 300 mg) ↓ annexin V-positive cells	↓ shrunken glomerular tuft ↓ loss of structural cohesion with atypical podocytes ↓ loss of nuclei ↓ tubular dilation with luminal congestion ↓ tubular epithelial cell vacuolization ↓ tubular shedding ↓ tubulo-interstitial lesions	Silymarin decreased systemic and renal oxidative damage, preserving renal function, morphological architectures antigenotoxic and antiapoptotic activities under exposure to radiocontrast agent in mice, leading to improved renal function	[52]
Adult Wistar Albino rats	Iodixanol/IV	Sphingosylphosphorylcholine/2, 10 µM/IP/3 day after iodixanol	↔ Cr ↓ BUN	↑ SOD ↓ MDA	↓ NO ↓ iNOS-positive cells	↓ TUNEL-positive cells	↓ widespread loss of brush border ↓ denudation of tubular cells ↓ tubule dilatation ↓ intratubular obstruction by granular casts	Sphingosyl-phosphoryl-choline reduced CIN via preventing oxidative stress and apoptosis, leading to improved renal function	[63]
Adult Sprague Dawley rats	Indomethacin/IV + L-NAME/IV treated with ioversol/IV	Sulforaphane/5 mg/kg/po/5 day prior to ioversol	↓ Cr ↓ BUN	↓ MDA ↑ SOD	–	↑ Nrf-2, NQO-1 and HO-1 gene expression ↑ Nrf-2 nuclear translocation ↑ HO-1 and NQO-1 protein levels	↓ tubular necrosis ↓ hemorrhagic casts	Sulforaphane ameliorated CIN via Nrf-2/HO-1 pathway, leading to improved renal function	[27]
Male C57BL/6 mice	Water deprivation 16 h + indomethacin/IP + L-NAME/IP treated with iohexol	GKT137831 (Nox1/4 inhibitor)/40 mg/kg/po/5 day prior to iohexol	↔ Cr ↓ BUN ↓ 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 degeneration ↓ 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	Inhibition of Nox1/4 prevented CIN via a reduction of oxidative stress and apoptosis, leading to improved renal function	[17]
Male Wistar albino rats	Dehydration 3 day treated with diatrizoate/IV	Carvedilol/2 mg/kg/po/3 day prior to diatrizoate Nebivolol/2 mg/kg/po/3 day prior to diatrizoate	↔ Cr ↔ BUN	↓ MDA ↑ TAC ↔ SOD	–	–	↓ interstitial inflammation ↓ tubular degeneration ↓ tubular dilatation	Both carvedilol and nebivolol attenuated oxidative stress but did not improve renal function	[57]
Female Wistar albino rats	Furosemide/SC + deprived of water for 24 h treated with iothalamate sodium/IV	8.4% NaHCO3/1 mL/IV/3 h prior to iothalamate	↔ Cr ↔ CrCl	↔ MDA ↓ GSH	↔ MPO ↔ NO	–	↓ % of tubular injury	Urinary alkalinization before IV contrast protected morphological change protection in rats but did not improve renal function	[64]

AKI, acute kidney injury; Bax, Bcl2-associated X protein; Bcl-2, B-cell lymphoma 2; BUN, blood urea nitrogen; CAT, catalase; CIN, contrast-induced nephropathy; CM, contrast media; Cr, creatinine; CrCl, creatinine clearance; Cyt c, cytochrome c; eNOS, endothelial nitric oxide synthase; ET-1, endothelin-1; FENa, fractional excretion of sodium; GFR, glomerular filtration rate; GSH, glutathione; GSH-Px, glutathione peroxidase; HO-1, heme oxygenase-1; HSA-Trx, recombinant human serum albumin-Thioredoxin-1 fusion protein; ICAM-1; intercellular cell adhesion molecule 1; IL, interleukin; iNOS, inducible nitric oxide synthase; IP, intraperitoneally; IV, intravenously; LC3, light-chain 3; L-NAME, N^ω-nitro-L-arginine methyl ester; MAPK, mitogen-activated protein kinase; MCP-1, monocyte chemotactic protein-1; MDA, malondialdehyde; MPO, myeloperoxidase; mRNA, messenger ribonucleic acid; MYPT-1, myosin light-chain phosphatase; NAC, N-acetylcysteine; NADPH, nicotinamide adenine dinucleotide phosphate; NAG, N-acetyl-β-glucosaminidase; NF-kB, nuclear factor-kB; NGAL, neutrophil gelatinase-associated lipocalin; NO, nitric oxide; Nrf-2, Nuclear factor erythroid-derived 2-like 2; OSI, oxidative stress index; PAI-1, plasminogen activator inhibitor 1; PCC, protein carbonyl content; PCR, polymerase chain reaction; PGC-1α, peroxisome proliferator-activated receptor-γ co-activator 1α; Pink1, PTEN-induced putative kinase; RBF, renal blood flow; ROCK-2, Rho kinase 2; RPF, renal plasma flow; RNA, ribonucleic acid; RVR, renal vascular resistance; SC, subcutaneously; SIRT1, sirtuin 1; SOD, superoxide dismutase; TAC, total antioxidant capacity; TBARS, thiobarbituric acid-reacting substances; TGF-1β, transforming growth factor-1β; TNF-α, tumor necrosis factor-α; TOS, total oxidant system; TUNEL, terminal deoxynucleotidyl transferase dUTP nick-end labeling; uKIM-1, urinary kidney injury molecule-1; VEGF, vascular endothelial growth factor; 8-OHdG, 8-hydroxy-2′-deoxyguanosine; ∆ψm, Mitochondrial membrane potential