Background: The present study aimed at investigating the effect of a novel antioxidant, hydrogen (H2) gas, on the severity of contrast-induced acute kidney injury (CIAKI) in a rat model. Methods: CIAKI was induced in rats by intravenous injection of a contrast medium, Ioversol, in addition to reagents inhibiting prostaglandin and nitric oxide synthesis. During the injection of these reagents, the rats inhaled H2 gas or control gas. Results: One day after the injection, serum levels of urea nitrogen were significantly lower in H2 gas-inhaling CIAKI rats (17.6 ± 2.3 mg/dl) than those in control gas-treated CIAKI rats (36.0 ± 7.3 mg/dl), although they both were elevated as compared to untreated rats (14.9 ± 0.9 mg/dl). Consistently, creatinine clearance in H2 gas-treated CIAKI rats was higher than that in control gas-treated counterparts. Renal histological analysis revealed that the formation of proteinaceous casts and tubular necrosis was improved by H2 gas inhalation. Mechanistic analyses showed that inhalation of H2 gas significantly reduced renal cell apoptosis, expression of cleaved caspase 3, and expression of an oxidative stress marker, 8-hydroxydeoxyguanosine, in injured kidneys. Conclusion: Results suggest that H2 gas inhalation is effective in ameliorating the severity of CIAKI in rats by reducing renal cell apoptosis and oxidative stress.

1.
Keaney JJ, Hannon CM, Murray PT: Contrast-induced acute kidney injury: how much contrast is safe? Nephrol Dial Transplant 2013;28:1376-1383.
[PubMed]
2.
Seeliger E, Sendeski M, Rihal CS, Persson PB: Contrast-induced kidney injury: mechanisms, risk factors, and prevention. Eur Heart J 2012;33:2007-2015.
[PubMed]
3.
Heyman SN, Rosen S, Khamaisi M, Idée JM, Rosenberger C: Reactive oxygen species and the pathogenesis of radiocontrast-induced nephropathy. Invest Radiol 2010;45:188-195.
[PubMed]
4.
Arakawa K, Suzuki H, Naitoh M, Matsumoto A, Hayashi K, Matsuda H, Ichihara A, Kubota E, Saruta T: Role of adenosine in the renal responses to contrast medium. Kidney Int 1996;49:1199-1206.
[PubMed]
5.
Bakris GL, Lass N, Gaber AO, Jones JD, Burnett JC Jr: Radiocontrast medium-induced declines in renal function: a role for oxygen free radicals. Am J Physiol 1990;258:F115-F120.
[PubMed]
6.
Sendeski M, Patzak A, Pallone TL, Cao C, Persson AE, Persson PB: Iodixanol, constriction of medullary descending vasa recta, and risk for contrast medium-induced nephropathy. Radiology 2009;251:697-704.
[PubMed]
7.
Cao C, Edwards A, Sendeski M, Lee-Kwon W, Cui L, Cai CY, Patzak A, Pallone TL: Intrinsic nitric oxide and superoxide production regulates descending vasa recta contraction. Am J Physiol Renal Physiol 2010;299:F1056-F1064.
[PubMed]
8.
Liu ZZ, Schmerbach K, Lu Y, Perlewitz A, Nikitina T, Cantow K, Seeliger E, Persson PB, Patzak A, Liu R, Sendeski MM: Iodinated contrast media cause direct tubular cell damage, leading to oxidative stress, low nitric oxide, and impairment of tubuloglomerular feedback. Am J Physiol Renal Physiol 2014;306:F864-F872.
[PubMed]
9.
Quintavalle C, Brenca M, De Micco F, Fiore D, Romano S, Romano MF, Apone F, Bianco A, Zabatta MA, Troncone G, Briguori C, Condorelli G: In vivo and in vitro assessment of pathways involved in contrast media-induced renal cells apoptosis. Cell Death Dis 2011;2:e155.
[PubMed]
10.
Lee HC, Sheu SH, Yen HW, Lai WT, Chang JG: JNK/ATF2 pathway is involved in iodinated contrast media-induced apoptosis. Am J Nephrol 2010;31:125-133.
[PubMed]
11.
Ohsawa I, Ishikawa M, Takahashi K, Watanabe M, Nishimaki K, Yamagata K, Katsura K, Katayama Y, Asoh S, Ohta S: Hydrogen acts as a therapeutic antioxidant by selectively reducing cytotoxic oxygen radicals. Nat Med 2007;13:688-694.
[PubMed]
12.
Nagatani K, Wada K, Takeuchi S, Kobayashi H, Uozumi Y, Otani N, Fujita M, Tachibana S, Nawashiro H: Effect of hydrogen gas on the survival rate of mice following global cerebral ischemia. Shock 2012;37:645-652.
[PubMed]
13.
Fukuda K, Asoh S, Ishikawa M, Yamamoto Y, Ohsawa I, Ohta S: Inhalation of hydrogen gas suppresses hepatic injury caused by ischemia/reperfusion through reducing oxidative stress. Biochem Biophys Res Commun 2007;361:670-674.
[PubMed]
14.
Hayashida K, Sano M, Ohsawa I, Shinmura K, Tamaki K, Kimura K, Endo J, Katayama T, Kawamura A, Kohsaka S, Makino S, Ohta S, Ogawa S, Fukuda K: Inhalation of hydrogen gas reduces infarct size in the rat model of myocardial ischemia-reperfusion injury. Biochem Biophys Res Commun 2008;373:30-35.
[PubMed]
15.
Kawamura T, Huang CS, Tochigi N, Lee S, Shigemura N, Billiar TR, Okumura M, Nakao A, Toyoda Y: Inhaled hydrogen gas therapy for prevention of lung transplant-induced ischemia/reperfusion injury in rats. Transplantation 2010;90:1344-1351.
[PubMed]
16.
Xie K, Yu Y, Pei Y, Hou L, Chen S, Xiong L, Wang G: Protective effects of hydrogen gas on murine polymicrobial sepsis via reducing oxidative stress and HMGB1 release. Shock 2010;34:90-97.
[PubMed]
17.
Xie K, Yu Y, Zhang Z, Liu W, Pei Y, Xiong L, Hou L, Wang G: Hydrogen gas improves survival rate and organ damage in zymosan-induced generalized inflammation model. Shock 2010;34:495-501.
[PubMed]
18.
Hayashida K, Sano M, Kamimura N, Yokota T, Suzuki M, Maekawa Y, Kawamura A, Abe T, Ohta S, Fukuda K, Hori S: H2 gas improves functional outcome after cardiac arrest to an extent comparable to therapeutic hypothermia in a rat model. J Am Heart Assoc 2012;1:e003459.
[PubMed]
19.
Agmon Y, Peleg H, Greenfeld Z, Rosen S, Brezis M: Nitric oxide and prostanoids protect the renal outer medulla from radiocontrast toxicity in the rat. J Clin Invest 1994;94:1069-1075.
[PubMed]
20.
Yokomaku Y, Sugimoto T, Kume S, Araki S, Isshiki K, Chin-Kanasaki M, Sakaguchi M, Nitta N, Haneda M, Koya D, Uzu T, Kashiwagi A: Asialoerythropoietin prevents contrast-induced nephropathy. J Am Soc Nephrol 2008;19:321-328.
[PubMed]
21.
Yamasowa H, Shimizu S, Inoue T, Takaoka M, Matsumura Y: Endothelial nitric oxide contributes to the renal protective effects of ischemic preconditioning. J Pharmacol Exp Ther 2005;312:153-159.
[PubMed]
22.
Toprak O, Cirit M, Tanrisev M, Yazici C, Canoz O, Sipahioglu M, Uzum A, Ersoy R, Sozmen EY: Preventive effect of nebivolol on contrast-induced nephropathy in rats. Nephrol Dial Transplant 2008;23:853-859.
[PubMed]
23.
Yoshida T, Yamashita M, Horimai C, Hayashi M: Smooth muscle-selective inhibition of nuclear factor-κB attenuates smooth muscle phenotypic switching and neointima formation following vascular injury. J Am Heart Assoc 2013;2:e000230.
[PubMed]
24.
Yoshida T, Kaestner KH, Owens GK: Conditional deletion of Krüppel-like factor 4 delays downregulation of smooth muscle cell differentiation markers but accelerates neointimal formation following vascular injury. Circ Res 2008;102:1548-1557.
[PubMed]
25.
Huang CS, Kawamura T, Toyoda Y, Nakao A: Recent advances in hydrogen research as a therapeutic medical gas. Free Radic Res 2010;44:971-982.
[PubMed]
You do not currently have access to this content.