Abstract
This study proposes the intravenous administration of glutathione (GSH) as a novel strategy to prevent contrast medium-induced renal oxidative stress. Renal oxidative stress is a critical cause of contrast-induced nephropathy (CIN). Recent reports have described that N-acetylcysteine (NAC) may prevent CIN by scavenging reactive oxygen species in the kidney. Twenty-one patients with reduced renal function who underwent coronary angiography (CAG) were equally assigned to the control, NAC and GSH (100 mg/min for 30 min before CAG) groups. CIN occurred in two patients, one in the control and the other in the NAC group. In the control group, the urinary lipid hydroperoxides (LOOHs) increased to 299.5 ± 94.4% of the baseline at 2 h after CAG (mean ± SE, p < 0.01). The increase in LOOHs was completely abolished in the GSH group (5.5 ± 8.8%, p = ns), but not in the NAC group (196.8 ± 81.3%, p < 0.05). In the control group, the serum GSH level fell by 9.4 ± 2.3% at 2 h after CAG (p < 0.01). The decrease was prevented in the GSH group (−1.8 ± 8.5%, p = ns), but not in the NAC group (−10.0 ± 3.3%, p < 0.05). The renal damage by contrast medium-induced oxidative stress occurs soon after CAG, and intravenous GSH is more effective in preventing the oxidative stress than oral NAC. This advantage may make GSH a potentially more effective therapeutic strategy against CIN.
Similar content being viewed by others
References
Kimura T, Morimoto T, Furukawa Y, Kita T (2009) Incidence of and risk factors for contrast-induced nephropathy after cardiac catheterization in Japanese patients. Circ J 73:1518–1522
Freeman RV, O’Donnell M, Share D, Meengs WL, Kline-Rogers E, Clark VL, DeFranco AC, Eagle KA, McGinnity JG, Patel K, Maxwell-Eward A, Bondie D, Moscucci M (2002) Nephropathy requiring dialysis after percutaneous coronary intervention and the critical role of an adjusted contrast dose. Am J Cardiol 90:1068–1073
Murphy SW, Barrett BJ, Parfrey PS (2000) Contrast nephropathy. J Am Soc Nephrol 11:177–182
Parfrey PS, Griffiths SM, Barrett BJ, Paul MD, Genge M, Withers J, Farid N, McManamon PJ (1989) Contrast material-induced renal failure in patients with diabetes mellitus, renal insufficiency, or both. A prospective controlled study. N Engl J Med 320:143–149
Rich MW, Crecelius CA (1990) Incidence, risk factors, and clinical course of acute renal insufficiency after cardiac catheterization in patients 70 years of age or older. A prospective study. Arch Intern Med 150:1237–1242
Tepel M, Aspelin P, Lameire N (2006) Contrast-induced nephropathy: a clinical and evidence-based approach. Circulation 113:1799–1806
Fishbane S, Durham JH, Marzo K, Rudnik M (2004) N-acetylcysteine in the prevention of radiocontrast-induced nephropathy. J Am Soc Nephrol 15:251–260
Gleeson TG, Bulugahapitiya S (2004) Contrast-induced nephropathy. Am J Roentgenol 183:1673–1689
Maeder M, Klein M, Fehr T, Rickli H (2004) Contrast nephropathy: review focusing on prevention. J Am Coll Cardiol 44:1763–1771
McCullough PA, Wolyn R, Rocher LL, Levin RN, O’Neill WW (1997) Acute renal failure after coronary intervention: incidence, risk factors, and relationship to mortality. Am J Med 103:368–375
Rihal CS, Textor SC, Grill DE, Berger PB, Ting HH, Best PJ, Singh M, Bell MR, Barsness GW, Mathew V, Garratt KN, Holmes DR Jr (2002) Incidence and prognostic importance of acute renal failure after percutaneous coronary intervention. Circulation 105:2259–2264
Bakris GL, Lass N, Gaber AO, Jones JD, Burnett JC Jr (1990) Radiocontrast medium-induced declines in renal function: a role for oxygen free radicals. Am J Physiol 258:F115–F120
Yoshioka T, Fogo A, Beckman JK (1992) Reduced activity of antioxidant enzymes underlies contrast media-induced renal injury in volume depletion. Kidney Int 41:1008–1015
Detrenis S, Meschi M, Musini S, Savazzi G (2005) Lights and shadows on the pathogenesis of contrast-induced nephropathy: state of the art. Nephrol Dial Transpl 20:1542–1550
Persson PB, Hansell P, Lis P (2005) Pathophysiology of contrast medium-induced nephropathy. Kidney Int 68:14–22
Marenzi G, Assanelli E, Marana I, Lauri G, Campodonico J, Grazi M, De Metrio M, Galli S, Fabbiocchi F, Montorsi P, Veglia F, Bartorelli AL (2006) N-acetylcysteine and contrast-induced nephropathy in primary angioplasty. N Engl J Med 354:2773–2782
Abbott WA, Bridges RJ, Meister A (1984) Extracellular metabolism of glutathione accounts for its disappearance from the basolateral circulation of the kidneys. J Biol Chem 259:15393–15400
Lash LH (2005) Role of glutathione transport processes in kidney function. Toxicol Appl Pharmacol 204:329–342
Cockcroft DW, Gault MH (1976) Prediction of creatinine clearance from serum creatinine. Nephron 16:31–41
Aebi S, Assereto R, Lauterburg BH (1991) High-dose intravenous glutathione in man. Pharmacokinetics and effects on cyst(e)ine in plasma and urine. Eur J Clin Invest 21:103–110
Oriana S, Böhm S, Spatti G, Zunino F, Di Re F (1987) A preliminary clinical experience with reduced glutathione as protector against cisplatin-toxicity. Tumori 73:337–340
Girotti AW (1998) Lipid hydroperoxide generation, turnover, and effector action in biological systems. J Lipid Res 39:1529–1542
Kato K, Sato N, Yamamoto T, Iwasaki YK, Tanaka K, Mizuno K (2008) Valuable markers for contrast-induced nephropathy in patients undergoing cardiac catheterization. Circ J 72:1499–1505
Zhou H, Kato A, Miyaji T, Yasuda H, Fujigaki Y, Yamamoto T, Yonemura K, Takebayashi S, Mineta H, Hishida A (2006) Urinary marker for oxidative stress in kidneys in cisplatin-induced acute renal failure in rats. Nephrol Dial Transpl 21:616–623
Yenicerioglu Y, Yilmaz O, Sarioglu S, Ormen M, Akan P, Celik A, Camsari T (2006) Effects of N-acetylcysteine on radiocontrast nephropathy in rats. Scand J Urol Nephrol 40:63–69
Trivedi HS, Moore H, Nasr S, Aggarwal K, Agrawal A, Goel P, Hewett J (2003) A randomized prospective trial to assess the role of saline hydration on the development of contrast nephrotoxicity. Nephron Clin Pract 93:29–34
Solomon RJ, Natarajan MK, Doucet S, Sharma SK, Staniloae CS, Katholi RE, Gelormini JL, Labinaz M, Moreyra AE, Investigators of the CARE Study (2007) Cardiac Angiography in Renally Impaired Patients (CARE) study: a randomized double-blind trial of contrast-induced nephropathy in patients with chronic kidney disease. Circulation 115:3189–3196
Thomsen HS, Morcos SK, Erley CM, Grazioloi L, Bonomo L, Ni Z (2008) The ACTIVE Trial: comparison of the effects on renal function of iomeprol-400 and idoixanol-320 in patients with chronic kidney disease undergoing abdominal computed tomography. Invest Radiol 43:170–178
Murphy MB, Murray C, Shorten GD (2001) Fenoldopam: a selective peripheral dopamine-receptor agonist for the treatment of severe hypertension. N Engl J Med 345:1548–1557
Briguori C, Colombo A, Airoldi F, Violante A, Castelli A, Balestrieri P, Paolo Elia P, Golia B, Lepore S, Riviezzo G, Scarpato P, Librera M, Focaccio A, Ricciardelli B (2004) N-acetylcysteine versus fenoldopam mesylate to prevent contrast agent-associated nephrotoxicity. J Am Coll Cardiol 44:762–765
Sankar D, Navaneethan SD, Singh S, Appasamy S, Wing RE, Sehgal AR (2009) Sodium bicarbonate therapy for prevention of contrast-induced nephropathy: a systematic review and meta-analysis. Am J Kidney Dis 53:617–627
Birck R, Krzossok S, Markowetz F, Schnülle P, van der Woude FJ, Braun C (2003) Acetylcysteine for prevention of contrast nephropathy: meta-analysis. Lancet 362:598–603
Gomes VO, Poli de Figueredo CE, Caramori P, Lasevitch R, Bodanese LC, Araújo A, Röedel AP, Caramori AP, Brito FS Jr, Bezerra HG, Nery P, Brizolara A (2005) N-acetylcysteine does not prevent contrast induced nephropathy after cardiac catheterisation with an ionic low osmolality contrast medium: a multicentre clinical trial. Heart 91:774–778
Oldemeyer JB, Biddle WP, Wurdeman RL, Mooss AN, Cichowski E, Hilleman DE (2003) Acetylcysteine in the prevention of contrast-induced nephropathy after coronary angiography. Am Heart J 146:E23
Harada D, Naito S, Kawauchi Y, Ishikawa K, Koshitani O, Hiraoka I, Otagiri M (2001) Determination of reduced, protein-unbound, and total concentrations of N-acetyl-l-cysteine and l-cysteine in rat plasma by postcolumn ligand substitution high-performance liquid chromatography. Anal Biochem 290:251–259
Olsson B, Johansson M, Gabrielsson J, Bolme P (1988) Pharmacokinetics and bioavailability of reduced and oxidized N-acetylcysteine. Eur J Clin Pharmacol 34:77–82
Scaduto RC Jr, Gattone VH 2nd, Martin LF, Yang HC (1991) Elevation of renal glutathione enhances ischemic injury. Ren Physiol Biochem 14:259–270
Prasad A, Andrews NP, Padder FA, Husain M, Quyyumi AA (1999) Glutathione reverses endothelial dysfunction and improves nitric oxide bioavailability. J Am Coll Cardiol 34:507–514
Zunino F, Pratesi G, Micheloni A, Cavalletti E, Sala F, Tofanetti O (1989) Protective effect of reduced glutathione against cisplatin-induced renal and systemic toxicity and its influence on the therapeutic activity of the antitumor drug. Chem Biol Interact 70:89–101
Tofanetti O, Cavalletti E, Besati A, Pratesi G, Pezzoni G, Zunino F (1985) Prevention of cyclophosphamide-induced urotoxicity by reduced glutathione and its effect on acute toxicity and antitumor activity of the alkylating agent. Cancer Chemother Pharmacol 14:188–193
Zager RA, Johnson AC, Hanson SY (2003) Radiographic contrast media-induced tubular injury: evaluation of oxidant stress and plasma membrane integrity. Kidney Int 64:128–139
Bohm S, Oriana S, Spatti G, Di Re F, Breasciani G, Pirovano C, Grosso I, Martini C, Caraceni A, Pilotti S, Zunino F (1999) Dose intensification of platinum compounds with glutathione protection as induction chemotherapy for advanced ovarian carcinoma. Oncology 57:115–120
Patti G, Nusca A, Chello M, Pasceri V, D’Ambrosio A, Vetrovec GW, Di Sciascio G (2008) Usefulness of statin pretreatment to prevent contrast-induced nephropathy and to improve long-term outcome in patients undergoing percutaneous coronary intervention. Am J Cardiol 101:279–285
Author information
Authors and Affiliations
Corresponding author
Appendix
Appendix
The molecular weights of NAC (C5H9NO3S) and GSH (C10H17N3O6S) are 163.2 and 307.4, respectively. The bioavailability of NAC has been shown to be 3.4–19.8%, implying that approximately 90% of NAC degenerates to cysteine, which can be synthesized to GSH in the liver [35, 36]. Since the total amount of NAC administered during this study was 2,820 mg (1,410 mg a day for 2 days), it is equivalent to 4,780 mg of GSH (2,820 mg/163.2 × 307.4 × 0.9).
Rights and permissions
About this article
Cite this article
Saitoh, T., Satoh, H., Nobuhara, M. et al. Intravenous glutathione prevents renal oxidative stress after coronary angiography more effectively than oral N-acetylcysteine. Heart Vessels 26, 465–472 (2011). https://doi.org/10.1007/s00380-010-0078-0
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00380-010-0078-0