nefrНефрологияNephrology (Saint-Petersburg)1561-62742541-9439Pavlov First Saint-Petersburg State Medical University10.24884/1561-6274-2006-10-4-72-76nefr-702Research ArticleОРИГИНАЛЬНЫЕ СТАТЬИ. ЭКСПЕРИМЕНТАЛЬНЫЕ ИССЛЕДОВАНИЯORIGINAL ARTICLES. EXPERIMENTAL INVESTIGATIONК МЕХАНИЗМУ ТОКСИЧЕСКОГО ДЕЙСТВИЯ ДОКСОРУБИЦИНА НА ПОЧКИON THE MECHANISM OF TOXIC EFFECT OF DOXORUBICIN ON THE KIDNEYSСаенкоЮ. В.SaenkoYu. V.

Кафедра фармакологии с курсом клинической фармакологии, кафедра терапии и профессиональных болезней, кафедра лучевой диагностики, лучевой терапии и онкологии медицинского факультета

ШутовА. М.ShutovA. M.

Кафедра фармакологии с курсом клинической фармакологии, кафедра терапии и профессиональных болезней, кафедра лучевой диагностики, лучевой терапии и онкологии медицинского факультета

МусинаР. Х.MusinaR. Kh.

Кафедра фармакологии с курсом клинической фармакологии, кафедра терапии и профессиональных болезней, кафедра лучевой диагностики, лучевой терапии и онкологии медицинского факультета 

Ульяновский государственный университетRussian Federation2006100420061047276Copyright © Саенко Ю.В., Шутов А.М., Мусина Р.Х., 20062006Саенко Ю.В., Шутов А.М., Мусина Р.Х.Saenko Y.V., Shutov A.M., Musina R.K.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/702

ЦЕЛЬ ИССЛЕДОВАНИЯ. Механизмы токсического действия доксорубицина (ДОК) на почки остаются неясными, что послужило основанием для уточнения влияния ДОК на клетки с использованием в качестве клеточной эукариотической модели Saccharomyces cerevisiae. МАТЕРИАЛ И МЕТОДЫ. В исследовании использовался штамм S. cerevisiae YPH499. Инкубацию клеток с различными концентрациями доксорубицина проводили в течение 24 часов. Степень повреждения ДНК оценивали по активности гена рибонуклеотидредуктазы-3 (RNR3). Определяли концентрацию восстановленного глутатиона (ГSH), окисленного глутатиона (ГSSГ), содержание малонового диальдегида (МДА). РЕЗУЛЬТАТЫ. ДОК вызывал снижение клеточной пролиферации, приводил к росту концентрации ГSH, при этом отмечался достоверный рост концентрации ГSSГ, но выраженный в меньшей степени. В контрольных экспериментах отношение ГSH/ГSSГ было 7,33±0,28, тогда как в экспериментах с 10, 20, 30, 40, 50 мкМ ДОК отношение ГSH/ГSSГ составляло 7,52±1,08 (p>0,05); 5,51±0,46 (p<0,01); 6,38±2,39 (p>0,05); 5,19±0,63 (p<0,01) и 5,05±0,70 (р<0,01), соответственно. ДОК вызывал увеличение экспрессии гена RNR3.Содержание малонового диальдегида существенно не изменялось. ЗАКЛЮЧЕНИЕ. При инкубации S. cerevisiae в среде, содержащей ДОК и глюкозу, увеличение ГSH, обусловленное экспрессией гена RNR3, компенсирует избыточное образование свободных радикалов и не ведет к свободно-радикальному повреждению биомолекул. В почках животных при введении ДОК не обеспечивается достаточной концентрации ГSH, и в этих условиях свободные радикалы индуцируют оксидативный стресс за счет редокс циклических реакций ДОК.

THE AIM of the investigation was to specify effects of doxorubicin (DOX) on renal cells using eukaryotic model Saccharomyces cerevisiae since the mechanisms of toxic effects of DOX on the kidneys still remain obscure. MATREIALS AND METHODS. The investigation was performed with strain S.cerevisiae YPH499. Incubation of the cells with different concentrations of DOX lasted 24 hours. The degree of injury of DNA was evaluated by activity of the ribonucleotide reductase -3 (RNR3). The concentration of reduced glutathione (G[1]SH), oxidized glutation (G-SSG), contents of malonic dialdehyde (MDA) were determined. RESULTS. DOX caused a decrease of cell proliferation, resulted in growing concentration of G-SH and so a reliable growth of the concentration of G[1]SSG was noted, but in less degree. In control experiments the ratio G-SH/G-SSG was 7.33±0.28 while in experiments with 10, 20, 30, 40, 50 mkM DOX the ratio G-SH/G-SSG was 7.52± 1.08 (p>0.05); 5.51±0.46 (p<0.01); 6.38±2.39 (p>0.05); 5.19±0.63 (p<0.01) and 5.05±0.70 (p<0.01) respectively. DOX induced expression of gene RNR3. The content of malonic dialdehyde did not substantially change. CONCLUSION. During the incubation of S.cerevisiae in the medium containing DOX and glucose an increase of G-SH due to expression of gene RNR3 compensates the redundant formation of free radicals and does not lead to free-radical damage of biomolecules. In the kidneys of animals administration of DOX fails to provide a sufficient concentration of G-SH and under these conditions free radicals induce oxidative stress at the expense of redox of cyclic reactions of DOX.

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