Abstract
Background/Aim: An imbalance in renal redox status contributes to progression of renal dysfunction. We investigated the effects of an oral charcoal adsorbent (AST-120) on renal redox status, superoxide production from renal mitochondria, and serum lipid peroxidation using chronic kidney disease (CKD) model rats. Methods: CKD was induced by 5/6 nephrectomy. CKD rats were divided into 2 groups: controls, and those treated with AST-120 for 20 weeks. We evaluated: (1) renal redox status by in vivo low-frequency electron spin resonance imaging (EPRI); (2) renal superoxide scavenging activity (SSA); (3) superoxide production from renal mitochondria; (4) immunostaining for Cu-Zn superoxide dismutase (SOD), and (5) oxidative stress markers including LDL-negative charge (LDL-CMF), serum lipid peroxide (LPO) and urinary hexanoyl-lysine (HEL). The effect of indoxyl sulfate, a uremic toxin, on mitochondrial superoxide production was also investigated. Results: AST-120 treatment improved renal function, renal SSA, renal mitochondrial superoxide production, renal SOD expression, renal redox status by EPRI, and oxidative stress profiles by LDL-CMF, LPO and urinary HEL. Addition of indoxyl sulfate increased mitochondrial superoxide production and AST-120 also decreased this. Conclusions: Improvements in the redox status and lipid peroxidation induced by AST-120 may delay the progression of CKD.
Journal Section:
Original Paper
References
1.
McCord JM, Wong K: Oxygen free radicals and tissue damage. Excerpta Med 1979;65:343–351.
2.
Freeman BA, Crapo JD: Biology of disease: free radicals and tissue injury. Lab Invest 1982;47:412–426.
[PubMed]
3.
Steinberg D, Parthasarathy S, Carew TE, Khoo JC, Witztum JL: Beyond cholesterol. Modifications of low-density lipoprotein that increase its atherogenicity. N Engl J Med 1989;320:915–924.
[PubMed]
4.
Nagase S, Aoyagi K, Gotoh M, Hirayama A, Tomida C, Shimozawa Y, Koyama A: Increased lipid peroxidation by rat liver microsomes in experimental renal failure. Nephron 1996;74:204–208.
[PubMed]
5.
Scheuer H, Gwinner W, Hohbach J, Grone EF, Brandes RP, Malle E, Olbricht CJ, Walli AK, Gröne HJ: Oxidant stress in hyperlipidemia-induced renal damage. Am J Physiol Renal Physiol 2000;278:F63–F74.
[PubMed]
6.
Owada S, Goto S, Bannai K, Hayashi H, Nishijima F, Niwa T: Indoxyl sulfate reduces superoxide scavenging activity in the kidneys of normal and uremic rats. Am J Nephrol 2008;28:446–454.
[PubMed]
7.
Hirayama A, Nagase S, Ueda A, Oteki T, Takada K, Obara M, Inoue M, Yoh K, Hirayama K, Koyama A: In vivo imaging of oxidative stress in ischemia-reperfusion renal injury using electron paramagnetic resonance. Am J Physiol Renal Physiol 2005;288:F597–F603.
[PubMed]
8.
Kamibayashi M, Oowada S, Kameda H, Okada T, Inanami O, Ohta S, Ozawa T, Makino K, Kotake Y: Synthesis and characterization of a practically better DEPMPO-type spin trap, 5-(2,2-dimethyl-1,3-propoxy cyclophosphoryl)-5-methyl-1-pyrroline N-oxide (CYPMPO). Free Radic Res 2006;40:1166–1172.
[PubMed]
9.
Ogura A, Oowada S, Kon Y, Hirayama A, Yasui H, Meike S, Kobayashi S, Kuwabara M, Inanami O: Redox regulation in radiation-induced cytochrome c release from mitochondria of human lung carcinoma A549 cells. Cancer Lett 2009;277:64–71.
[PubMed]
10.
Sanaka T, Akizawa T, Koide K, Koshikawa S: Clinical analysis of retrospective responding patients administrated with oral adsorbent in chronic kidney disease secondary to chronic glomerulonephritis. Ther Apher Dial 2003;7:269–278.
[PubMed]
11.
Sanaka T, Akizawa T, Koide K, Koshikawa S: Protective effect of an oral adsorbent on renal function in chronic kidney disease: determinants of its efficacy in diabetic nephropathy. Ther Apher Dial 2004;8:232–240.
[PubMed]
12.
Yoshida Y, Sakai T, Ise M: Effects of oral adsorbent in the rat model of chronic kidney disease. Nephron 1992;62:305–314.
[PubMed]
13.
Niwa T, Miyazaki T, Hashimoto N, Hayashi H, Ise M, Uehara Y, Maeda K: Suppressed serum and urine levels of indoxyl sulfate by oral adsorbent in experimental uremic rats. Am J Nephrol 1992;12:201–206.
[PubMed]
14.
Kido T, Kurata H, Matsumoto A, Tobiyama R, Musha T, Hayashi K, Tamai S, Utsunomiya K, Tajima N, Fidge N, Itakura H, Kondo K: Lipoprotein analysis using agarose gel electrophoresis and differential staining of lipids. J Atheroscler Thromb 2001;8:7–13.
[PubMed]
15.
Sato I, Taniguchi T, Ishikawa U, Kusuki M, Hayashi F, Mukai M, Kawano S, Kondo S, Yamashita S, Kumagai S: The lipoprotein fraction between VLDL and LDL detected by biphasic agarose gel electrophoresis reflects serum remnant lipoprotein and Lp(a) concentrations. J Atheroscler Thromb 2006;13:55–61.
[PubMed]
16.
Yagi K: Assay for blood plasma or serum; in Packer L (ed): Methods in Enzymology. New York, Academic Press, 1984, vol 105, pp 328–331.
17.
Kato Y, Mori Y, Makino Y, Morimitsu Y, Hiroi S, Ishikawa T, Osawa T: Formation of Nε-(hexanonyl)lysine in protein exposed to lipid hydroperoxide. A plausible marker for lipid hydroperoxide-derived protein modification. J Biol Chem 1999;274:20406–20414.
[PubMed]
18.
Hardy M, Rockenbauer A, Vasquez-Vivar J, Felix C, Lopez M, Srinivasan S, Avadhani N, Tordo P, Kalyanaraman B: Detection, Characterization, and decay kinetics of ROS and thiyl adducts of mito-DEPMPO spin trap. Chem Res Toxicol 2007;20:1053–1060.
[PubMed]
19.
Aufenangur J, Haux P, Kattermann R: Improved method for enzymic determination of cholesterol in lipoproteins separated by electrophoresis on thin layer agarose gels. J Clin Chem Clin Biochem 1989;27:807–813.
[PubMed]
20.
Winkler K, Nauck M, Siekmeier R, Marz W, Wieland H: Determination of triglycerides in lipoproteins separated by agarose gel electrophoresis. J Lipid Res 1995;36:1839–1847.
[PubMed]
21.
Yano M, Inoue M, Maehata E, Shiba T, Yamakado M, Hirabayashi Y, Taniyama M, Suzuki S: Increased electronegative charge of serum low-density lipoprotein in patients with diabetes mellitus. Clin Chim Acta 2004;340:93–98.
[PubMed]
22.
Miyazaki N, Aoyama I, Ise M, Seo H, Niwa T: An oral sorbent reduces overload of indoxyl sulphate and gene expression of TGF-β1 in uraemic rat kidneys. Nephrol Dial Transplant 2000;15:1773–1781.
[PubMed]
23.
Niwa T, Ise M: Indoxyl sulfate, a circulating uremic toxin, stimulates the progression of glomerular sclerosis. J Lab Clin Med 1994;124:96–104.
[PubMed]
24.
Niwa T, Ise M, Miyazaki M: Progression of glomerular sclerosis in experimental uremic rats by administration of indole, a precursor of indoxyl sulfate. Am J Nephrol 1994;14:207–212.
[PubMed]
25.
Moorhead JF, Chan MK, EI-Nahas M, Varghese Z: Lipid nephrotoxicity in chronic progressive glomerular and tubulo-interstitial disease. Lancet 1982;2:1309–1311.
[PubMed]
26.
Kasiske BL, O’Donnell MP, Schmitz PG, Keane WF: The role of lipid abnormalities in the pathogenesis of chronic, progressive renal disease. Adv Nephrol Necker Hosp 1991;20:109–125.
[PubMed]
27.
Keane WF: Lipids and progressive renal failure. Wien Klin Wochenschr 1996;108:420–424.
[PubMed]
28.
Hattori M, Nikotic-Paterson DJ, Miyazaki K, Isbel NM, Lan HY, Atkin RC, Kawaguchi H, Ito K: Mechanisms of glomerular macrophage infiltration in lipid-induced renal injury. Kidney Int Suppl 1999;71:S47–S50.
[PubMed]
29.
Abrass CK: Cellular lipid metabolism and the role of lipids in progressive renal disease. Am J Nephrol 2004;24:46–53.
[PubMed]
30.
Trevisan R, Dodensini AR, Lepore G: Lipids and renal disease. J Am Soc Nephrol 2006;17(suppl 2):S145–S147.
31.
Vaziri ND: Dyslipidemia of chronic kidney disease: the nature, mechanisms, and potential consequences. Am J Physiol 2006;290:F262–F272.
[PubMed]
32.
Yamakado M, Ise M: Mechanism of oral absorbent AST-120 in lipid abnormalities in experimental uremic rats. Kidney Int 1999;56(suppl 71):S190–S192.
33.
Sato T, Miyazaki S, Sakemi T, Nohri S: The oral adsorbent AST-120 attenuates the progression of hyperlipidemia and glomerulosclerosis in spontaneous hypercholesterolemic rats (SHCRs). Clin Exp Nephrol 2000;4:18–23.
34.
Sato T, Liang K, Vaziri ND: Protein restriction and AST-120 improve lipoprotein lipase and VLDL receptor in focal glomerulosclerosis. Kidney Int 2003;64:1780–1786.
[PubMed]
35.
Shimoishi K, Anraku M, Kitamura K, Tasaki Y, Taguchi K, Hashimoto M, Fukunaga E, Maruyama T, Otagiri M: An oral adsorbent, AST-120 protects against the progression of oxidative stress by reducing the accumulation of indoxyl sulfate in the systemic circulation in renal failure. Pharm Res 2007;24:1283–1289.
[PubMed]
36.
Akizawa T, Asano Y, Morita S, Wakita T, Onishi Y, Fukuhara S, Gejyo F, Matsuo S, Yorioka N, Kurokawa K: on behalf of the CAP-KD Study Group. Effect of a carbonaceous oral adsorbent on the progression of CKD: A multicenter, randomized, controlled trial. Am J Kid Dis 2009;54:459–467.
[PubMed]
© 2010 S. Karger AG, Basel
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
2010
You do not currently have access to this content.
