nefrНефрологияNephrology (Saint-Petersburg)1561-62742541-9439Pavlov First Saint-Petersburg State Medical University10.24884/1561-6274-2005-9-1-69-74nefr-796Research ArticleЭКСПЕРИМЕНТАЛЬНЫЕ ИССЛЕДОВАНИЯФАРМАКОЛОГИЧЕСКАЯ КОРРЕКЦИЯ ОКСИДАТИВНОГО СТРЕССА, ИНДУЦИРОВАННОГО ДОКСОРУБИЦИНОМ, В ПОЧКАХ КРЫСPHARMACOLOGICAL CORRECTION OF DOXORUBICIN-INDUCED OXIDATIVE STRESS IN KIDNEYS OF RATSСаенкоЮ. В.SaenkoYu. V.

Кафедра фармакологии и кафедра терапии и профессиональных болезней, медицинский факультет

НапалковаС. М.NapalkovaS. M.

Кафедра фармакологии и кафедра терапии и профессиональных болезней, медицинский факультет

ШутовА. М.ShutovA. M.

Кафедра фармакологии и кафедра терапии и профессиональных болезней, медицинский факультет

БрынскихГ. Т.BrynskikhG. T.

Кафедра фармакологии и кафедра терапии и профессиональных болезней, медицинский факультет

Ульяновский государственный университетRussian Federation200510012005916974Copyright © Саенко Ю.В., Напалкова С.М., Шутов А.М., Брынских Г.Т., 20052005Саенко Ю.В., Напалкова С.М., Шутов А.М., Брынских Г.Т.Saenko Y.V., Napalkova S.M., Shutov A.M., Brynskikh G.T.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/796

ЦЕЛЬ ИССЛЕДОВАНИЯ. Доксорубицин (ДОК) – антрациклиновый антибиотик с широким спектром противоопухолевой активности. Использование ДОК сдерживается кардио и нефротоксичностью препарата, которая реализуется, в том числе, через индукцию оксидативного стресса. Целью исследования явилось определение возможности фармакологи ческой коррекции оксидативного стресса, вызванного доксорубицином, в почках крыс. МАТЕРИАЛ И МЕТОДЫ. Исследование выполнено на 35 самцах беспородных белых крыс. Животные были разделены на 5 групп: контрольная группа (контроль, n=7), группа, в которой животным внутрибрюшинно водился доксорубицин из расчета 7,5 мг/кг массы (ДОК, n=7); группа, в которой животным перед инъекцией ДОК внутривенно вводили гормон эпифиза мелатонин в дозе 1 мг/кг (МЕЛ, n = 7), группа, в которой животным перед инъекцией ДОК внутривенно вводили аминокислоту глицин в дозе 50 мг/ кг (глицин, n = 7), группа, в которой животным перед инъекцией ДОК внутривенно вводили унитиол в дозе 5 мг/кг (унитиол, n = 7). Забой животных проводили через 24 часа путем декапитации. В гомогенате ткани почки исследовали содержание восстановленного глутатиона (ГSH), активность глютатион-трансферазы (ГSТ), активность цитоплазматической НАД(Ф)Н: хинон оксидоредуктазы 1 (НХО1), активность глутатион редуктазы (ГР), содержание белковых карбонильных групп. РЕЗУЛЬТАТЫ. Введение доксорубицина приводило к снижению уровня ГSH и активности ГР. Разницы в содержании белковых карбонильных групп не отмечено. Предварительное введение мелатонина и глицина приводило к нормализации ГSH, активности ГР и увеличению активности НХО 1 в ткани почек. ЗАКЛЮЧЕНИЕ. Гормон эпифиза мелатонин и аминокислота глицин ослабляют проявления оксидативного стресса, индуцированного доксорубицином, в почках крыс.

THE AIM of the investigation was Doxorubicin (DOX) as a widely used anthracycline antibiotic. Administration of DOX is limited due to cardio and renal toxicity because of oxidative stress. Our aim was to investigate early nephrotoxic effects of a single dose of DOX and impact of pretreatment with melatonin, glycine and unithiol. MATERIAL AND METHODS. The animals (35 rats) were divided into 5 groups. One group (Cgroup, n=7) was a control, one group (DOXgroup, n=7) received DOX (7.5 mg/kg, i.p.), one group (Mgroup, n=7) was pretreated with melatonin (1mg/kg, i.v.), one group (Ggroup, n=7) was pretreated with glycine (50 mg/kg, i.v.), one group (Ugroup, n=7) was pretreated with unithiol (5 mg/kg, i.v.).The rats were decapitated within 24 hours. The content of glutathione (GSH), glutathione reductase, NAD(P)H:quinone oxidoreductase, glutathioneStransferase and protein carbonyl group in the homogenate of renal mass were detected. RESULTS. Less concentration of GSH was detected in the renal tissue in the DOXgroup as compared with the Cgroup of rats. There were lower levels of GSH in DOXgroup as compared with Mgroup. Activity of glutathione reductase was lower in the DOXgroup than in the Cgroup. There was no difference in the content of protein carbonyl groups. Pretreatment with melatonin and glycin resulted in normalization of GSH levels. CONCLUSION. It was shown that pretreatment with melatonin and glycin reduced the DOX induced renal damage in rats by means of restoration of GSH in the renal tissue.

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