nefrНефрологияNephrology (Saint-Petersburg)1561-62742541-9439Pavlov First Saint-Petersburg State Medical University10.24884/1561-6274-2005-9-2-96-100nefr-763Research ArticleЭКСПЕРИМЕНТАЛЬНЫЕ ИССЛЕДОВАНИЯЭРИТРОПОЭТИН СНИЖАЕТ ПРОЯВЛЕНИЯ ОКСИДАТИВНОГО СТРЕССА, ИНДУЦИРОВАННОГО ДОКСОРУБИЦИНОМ, В ПОЧКАХ КРЫСERYTHROPOIETIN ATTENUATES MANIFESTATIONS OF OXIDATIVE DOXORUBICIN"INDUCED STRESS IN RAT KIDNEYSСаенкоЮ. В.SaenkoYu. V.

Кафедра фармакологии, Кафедра терапии и профессиональных болезней, медицинский факультет

ШутовА. М.ShutovA. M.

Кафедра фармакологии, Кафедра терапии и профессиональных болезней, медицинский факультет

НапалковаС. М.NapalkovaS. M.

Кафедра фармакологии, Кафедра терапии и профессиональных болезней, медицинский факультет

СеливановаО. С.SelivanovaO. S.

Кафедра фармакологии, Кафедра терапии и профессиональных болезней, медицинский факультет

Ульяновский государственный университетRussian Federation2005100220059296100Copyright © Саенко Ю.В., Шутов А.М., Напалкова С.М., Селиванова О.С., 20052005Саенко Ю.В., Шутов А.М., Напалкова С.М., Селиванова О.С.Saenko Y.V., Shutov A.M., Napalkova S.M., Selivanova O.S.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://journal.nephrolog.ru/jour/article/view/763

ЦЕЛЬ ИССЛЕДОВАНИЯ. Целью исследования явилось определение возможности коррекции эритропоэтином оксидатив ного стресса, индуцированного доксорубицином, в почках крыс. МАТЕРИАЛ И МЕТОДЫ. Исследование выполнено на беспородных белых крысах. Одной группе животных (группа ДОК, n=7) внутрибрюшинно вводили доксорубицин, другой внутрибрюшинно доксорубицин с одновременным внутривенным введением эритропоэтина (группа ЭПО, n=7). Забой животных, включая контрольную группу (группа Контроль, n=7), проводили через 24 часа. В гомогенате тканей почек исследовали содержание восстановленного глутатиона (ГSH), активность глутатионSтрансферазы (ГSТ), активность цитоплазматической НАД(Ф)Н:хинон оксидоредуктазы 1 (НХО 1), активность глутатион редуктазы (ГР), содержание белковых карбонильных групп. РЕЗУЛЬТАТЫ. Введение доксорубицина привело к снижению уровня ГSH (0,061±0,017 против 0,089±0,011 мкмоль/мг ткани в контрольной группе, p<0,05) и активности ГР (62,10±8,04 против 85,80±7,18 нмоль/мин/мг белка в контрольной группе, p<0,05) в гомогенате почек. Введение эритропоэтина предотвращало снижение ГSH и активности ГР и приводило к увеличению активности НХО 1 в гомогенате почек. Разницы в содержании белковых карбонильных групп в гомогенате почек в исследуемых группах животных не отмечено. ЗАКЛЮЧЕНИЕ. Эритропоэтин ослабляет проявления оксидативного стресса, вызванного доксорубицином, в почках крыс.

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.

глутатиондоксорубициноксидативный стрессэритропоэтинerythropoietinglutathionedoxorubicinoxidative stresskidneyИсследование поддержано грантом «Университеты России», Грант УР 11.01.029ReferencesAbdelrahman EJ, Sharples MC, McDonald AF et al. Erythropoietin attenuates the tissue injury associated with hemorrhagic shock and myocardial ischemia. Shock 2004; 22: 6369Abdelrahman EJ, Sharples MC, McDonald AF et al. Erythropoietin attenuates the tissue injury associated with hemorrhagic shock and myocardial ischemia. Shock 2004; 22: 6369Anusevicius 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: 254256Anusevicius 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: 254256Arola O, Saraste A, Pulkki K. Acute doxorubicin cardiotoxicity involves cardiomyocyte apoptosis. Cancer Res 2000; 60: 17891792Arola O, Saraste A, Pulkki K. Acute doxorubicin cardiotoxicity involves cardiomyocyte apoptosis. Cancer Res 2000; 60: 17891792Basser RL, Green MD. Strategies for prevention of anthracycline cardiotoxicity. Cancer Treat Rev 1993; 19: 57–77Basser RL, Green MD. Strategies for prevention of anthracycline cardiotoxicity. Cancer Treat Rev 1993; 19: 57–77Bradford MM. A rapid and sensitive method for quantitation of microgram quantities of protein utilizing the principle of proteindye binding. Annal Biochem 1976; 72: 248 254Bradford MM. A rapid and sensitive method for quantitation of microgram quantities of protein utilizing the principle of proteindye binding. Annal Biochem 1976; 72: 248 254Carlberg I, Mannervik B. Purification and characterization of the flavoenzyme glytathione reductase from rat liver. J Biol Chem 1975; 250: 54755480Carlberg I, Mannervik B. Purification and characterization of the flavoenzyme glytathione reductase from rat liver. J Biol Chem 1975; 250: 54755480Celik 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: 2258–2263Celik 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: 2258–2263Dziegiel 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: 95100Dziegiel 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: 95100Ellman GL. Tissue sulfhydryl groups. Arch Biochem Biophys 1972; 82: 7077Ellman GL. Tissue sulfhydryl groups. Arch Biochem Biophys 1972; 82: 7077Fisher 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: 359–370Fisher 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: 359–370Habig WG, Pabst MJ, Jakoby WB. Glutathione S transferase. The first enzymic step in mercapturic acid formation. J Biol Chem 1974; 249: 71307139Habig WG, Pabst MJ, Jakoby WB. Glutathione S transferase. The first enzymic step in mercapturic acid formation. J Biol Chem 1974; 249: 71307139Klatt P, Lamas S. Regulation of protein function by S glutathiolation in response to oxidative stress. Eur J Biochem 2000; 267: 49284944Klatt P, Lamas S. Regulation of protein function by S glutathiolation in response to oxidative stress. Eur J Biochem 2000; 267: 49284944Levin RL, Garland D, Oliver CN et al. Determination of carbonyl content in oxidatively modified proteins. Methods Enzym 1990; 186: 464478Levin RL, Garland D, Oliver CN et al. Determination of carbonyl content in oxidatively modified proteins. Methods Enzym 1990; 186: 464478Minotti G, Cairo G, Monti E. Role of iron in anthracycline cardiotoxicity: new tunes for an old song? FASEB J 1999; 13: 199212Minotti G, Cairo G, Monti E. Role of iron in anthracycline cardiotoxicity: new tunes for an old song? FASEB J 1999; 13: 199212Parsa С, Kim J, Riel R et al. Cardioprotective effects of erythropoietin in the reperfused ischemic heart. J Biol Chem 2004; 279: 2065520662Parsa С, Kim J, Riel R et al. Cardioprotective effects of erythropoietin in the reperfused ischemic heart. J Biol Chem 2004; 279: 2065520662Powis G. Free radical formation by antitumor quinones. Free Rad Biol Med 1989; 6: 63101Powis G. Free radical formation by antitumor quinones. Free Rad Biol Med 1989; 6: 63101Schafer 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: 11911212Schafer 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: 11911212Siegel D, Gustafson DL, Dehn DL et al. NAD(P)H:Quinone Oxidoreductase 1: role as a superoxide scavenger. Mol Pharmacol 2004; 65: 12381247Siegel D, Gustafson DL, Dehn DL et al. NAD(P)H:Quinone Oxidoreductase 1: role as a superoxide scavenger. Mol Pharmacol 2004; 65: 12381247Sun X, Zhou Z, Kang JY. Attenuation of doxorubicin toxicity in metallothioneinoverexpressing transgenic mouse heart. Cancer Res 2001; 61: 33823387Sun X, Zhou Z, Kang JY. Attenuation of doxorubicin toxicity in metallothioneinoverexpressing transgenic mouse heart. Cancer Res 2001; 61: 33823387Wang X. The expanding role of mitochondria in apoptosis. Genes Dev 2001; 15: 29222933Wang X. The expanding role of mitochondria in apoptosis. Genes Dev 2001; 15: 29222933

The authors declare that there are no conflicts of interest present.