ERYTHROPOIETIN ATTENUATES MANIFESTATIONS OF OXIDATIVE DOXORUBICIN"INDUCED STRESS IN RAT KIDNEYS
https://doi.org/10.24884/1561-6274-2005-9-2-96-100
Abstract
THE AIM of the investigation was to determine possibilities of erythropoietin correction of oxidative doxorubicin induced stress in rat kidneys. MATREIAL AND METHODS. The investigation was fulfilled in white rats. One group of animals (n=7) was given intraperitoneal injections of doxorubicin, in the other group doxorubicin was injected intraperitoneally simultaneously with intravenous injection of erythropoietin (n=7). The animals including a control group (n=7) were killed in 24 hours. The content of the reduced glutathione (GSH), activity of glutathioneStransferase (GST), activity of cytoplasm NADPH:quinone oxidoreductase 1 (HXO 1), activity of glutathione reductase (GR), the content of protein carbonyl groups were investigated in homogenate of the kidney tissue. RESULTS. The introduction of doxorubicin resulted in lower level of GSH (0,061±0.017 versus 0.089±0.011 mkmol/mg of tissue in the control group, p<0.05) and activity of GR (62.10±8.04 versus 85.80±7.18 nmol/min/mg of protein in the control group, p<0.05) in the kidney homogenate. The introduction of erythropoietin prevented attenuation of GSH and activity of GR and led to increased activity of HXO 1 in the kidney homogenate. CONCLUSION. No difference was noted between the content of protein carbonyl groups in the kidney homogenate in the investigated groups of animals.
About the Authors
Yu. V. Saenko
Ульяновский государственный университет
Russian Federation
Russian Federation
A. M. Shutov
Ульяновский государственный университет
Russian Federation
Russian Federation
S. M. Napalkova
Ульяновский государственный университет
Russian Federation
Russian Federation
O. S. Selivanova
Ульяновский государственный университет
Russian Federation
Russian Federation
References
1. Abdelrahman EJ, Sharples MC, McDonald AF et al. Erythropoietin attenuates the tissue injury associated with hemorrhagic shock and myocardial ischemia. Shock 2004; 22: 6369
2. Anusevicius Z, Sarlauscas J, Cenas N. Twoelectron reduction of quinones by rat liver NAD(P)H:quinone oxidoreductase: quantitative structureactivity relationships. Arch Biochem Biophys 2002; 404: 254256
3. Arola O, Saraste A, Pulkki K. Acute doxorubicin cardiotoxicity involves cardiomyocyte apoptosis. Cancer Res 2000; 60: 17891792
4. Basser RL, Green MD. Strategies for prevention of anthracycline cardiotoxicity. Cancer Treat Rev 1993; 19: 57–77
5. Bradford MM. A rapid and sensitive method for quantitation of microgram quantities of protein utilizing the principle of proteindye binding. Annal Biochem 1976; 72: 248 254
6. Carlberg I, Mannervik B. Purification and characterization of the flavoenzyme glytathione reductase from rat liver. J Biol Chem 1975; 250: 54755480
7. Celik A, Gokmen N, Erbayraktar S et al. Erythropoietin prevents motor neuron apoptosis and neurologic disability in experimental spinal cord ischemic injury. Proc Natl Acad Sci USA 2002; 99: 2258–2263
8. Dziegiel P, Suder E, Surowiak P et al. Role of exogenous melatonin in reducing the nephrotoxic effect of daunorubicin and doxorubicin in the rat. J Pineal Res 2002; 33: 95100
9. Ellman GL. Tissue sulfhydryl groups. Arch Biochem Biophys 1972; 82: 7077
10. Fisher GR, Gutierrez PL. Free radical formation and DNA strand breakage during metabolism of diaziquone by NAD(P)H quinineacceptor oxidoreductase (DTdiaphorase) and NADPHcytochrome c reductase. Free Radic Biol Med 1991; 10: 359–370
11. Habig WG, Pabst MJ, Jakoby WB. Glutathione S transferase. The first enzymic step in mercapturic acid formation. J Biol Chem 1974; 249: 71307139
12. Klatt P, Lamas S. Regulation of protein function by S glutathiolation in response to oxidative stress. Eur J Biochem 2000; 267: 49284944
13. Levin RL, Garland D, Oliver CN et al. Determination of carbonyl content in oxidatively modified proteins. Methods Enzym 1990; 186: 464478
14. Minotti G, Cairo G, Monti E. Role of iron in anthracycline cardiotoxicity: new tunes for an old song? FASEB J 1999; 13: 199212
15. Parsa С, Kim J, Riel R et al. Cardioprotective effects of erythropoietin in the reperfused ischemic heart. J Biol Chem 2004; 279: 2065520662
16. Powis G. Free radical formation by antitumor quinones. Free Rad Biol Med 1989; 6: 63101
17. Schafer QF, Buettiner GR. Redox environment of the cell as viewed through the redox state of the glutathione disulfide/ glutathione couple. Free Rad Biol Med 2001; 30: 11911212
18. Siegel D, Gustafson DL, Dehn DL et al. NAD(P)H:Quinone Oxidoreductase 1: role as a superoxide scavenger. Mol Pharmacol 2004; 65: 12381247
19. Sun X, Zhou Z, Kang JY. Attenuation of doxorubicin toxicity in metallothioneinoverexpressing transgenic mouse heart. Cancer Res 2001; 61: 33823387
20. Wang X. The expanding role of mitochondria in apoptosis. Genes Dev 2001; 15: 29222933
Review
For citations:
Saenko Yu.V., Shutov A.M., Napalkova S.M., Selivanova O.S. ERYTHROPOIETIN ATTENUATES MANIFESTATIONS OF OXIDATIVE DOXORUBICIN"INDUCED STRESS IN RAT KIDNEYS. Nephrology (Saint-Petersburg). 2005;9(2):96-100. (In Russ.) https://doi.org/10.24884/1561-6274-2005-9-2-96-100
Views:
315
Email this article 