The effect of 2-benzamido-2-(2-oxoindolin-3-iliden) acetic acid derivative on the activity of lipid peroxidation processes and the antioxidant defense in chronic hypobaric hypoxia


  • I. I. Zamorskii Higher State Educational Institution of Ukraine «Bukovinian State Medical University», Ukraine
  • Yu. S. Bukataru Higher State Educational Institution of Ukraine «Bukovinian State Medical University», Ukraine
  • S. V. Kolisnyk National University of Pharmacy, Ukraine



antihypoxants, chronic hypobaric hypoxia, 2-benzamido-2-(2-oxoindolin-3-iliden) acetic acid derivative, mexidol


Hypoxia is a typical pathological process developing due to the decreased concentration of oxygen in the organism or in the particular tissues and organs, as well as disturbances of oxygen utilization during biological oxidation.
Aim. To determine the antihypoxic and antioxidant activity of the ZNM derivative of 2-benzamido-2-(2-oxoindolin-3-iliden) acetic acid in the brain and blood plasma of rats under the conditions of chronic hypobaric hypoxia (CHH) by the indicators of the lipid peroxidation processes activity and the state of the antioxidant defense.
Materials and methods. The studies were conducted under the conditions of CHH modeled by the standard method. The ZNM substance in the dose of 15 mg/kg and the reference drug mexidol in the dose of 100 mg/kg were injected
intraperitoneally starting from the 14th day of the experiment 30 min prior to the hypoxia simulation. Results. In the group of animals treated with ZNM a significant decrease in the content of malondialdehyde in the blood plasma and brain structures (by 1.2 and 1.1 times, respectively), as well as in the content of oxidative modified proteins (by 1.2 times in the blood plasma and 1.4 times in the brain tissue) was observed. The content of ceruloplasmin in the
blood plasma decreased by 1.7 times; the content of SH-groups increased by 3.1 times; the catalase activity increased by 1.2 times in the blood plasma, and by 1.9 times in brain homogenates. The reduced glutathione level in brain homogenates increased by 1.4 times; the glutathione peroxidase activity significantly increased by 2.1 times in the blood plasma and by 1.3 times in brain homogenates compared to the model pathology group.
Conclusions. It has been found that both mexidol and the ZNM substance demonstrate a significant antioxidant activity under the conditions of CHH by stabilizing the balance between prooxidant and antioxidant systems of the body in rats, and it is particularly important in oxidative stress caused by chronic hypoxia.

Author Biographies

I. I. Zamorskii, Higher State Educational Institution of Ukraine «Bukovinian State Medical University»

Doctor of Medicine (Dr. habil.), professor, head of the Pharmacology Department

Yu. S. Bukataru, Higher State Educational Institution of Ukraine «Bukovinian State Medical University»

teaching assistant of the Pharmacology Department

S. V. Kolisnyk, National University of Pharmacy

Doctor of Pharmacy (Dr. habil.), professor of the Analytical Chemistry Department


Зарубина, И. В. Молекулярная фармакология антигипоксантов / И. В. Зарубина, П. Д. Шабанов. – СПб.: ООО «Изд-во Н-Л», 2004. – 368 с. – («Обзоры по клинической фармакологии и лекарственной терапии»; вип. 2).

Андреева, Н. Н. Экспериментальные и клинические аспекты применения мексидола при гипоксии / Н. Н. Андреева // Мед. альманах. – 2009. – № 4. – С. 193-197.

Катунина, Н. П. Об изучении влияния антигипоксантов и новых производных 3-оксипиридина на выживаемость мышей в условиях острой гипоксии / Н. П. Катунина // Наука и современность. – 2010. – № 5. – С. 298-300.

Лукьянова, Л. Д. Молекулярные механизмы тканевой гипоксии и адаптация организма / Л. Д. Лукьянова // Фізіол. журн. – 2003. – Т. 49, № 3. – С. 17-35.

Основные механизмы формирования защиты головного мозга при адаптации к гипоксии / А. А. Солкин, Н. Н. Белявский, В. И. Кузнецов, А. Г. Николаева // Вестник ВГМУ. – 2012. – Т. 11, № 1. – С. 6-14.

Screening of derivatives of 2-(benzoyilamino)(1-R-2-oxoindolin-3-ylidene)acetic acid under the conditions of acute hypobaric hypoxia / I. I. Zamorskii, Y. S. Bukataru, E. L. Lenga et al. // Вісник фармації. – 2016. – № 1. – С. 67-70.

Важнича, О. М. Антистресорна активність мексидолу і роль структурних компонентів препарату в її реалізації / О. М. Важнича // Клінічна фармація. – 2001. – Т. 5, № 2. – С. 60-63.

Зв’язок «структура-антигіпоксична активність» у ряду похідних 2-бензамідо-2-(2-оксоіндолініліден-3)-оцтової ислоти / С. В. Колісник, Н. П. Кононенко, Д. В. Гаман, О. М. Котенко // Вісник фармації. – 2011. – № 4. – С. 64-66.

Пасевич, С. П. Антиоксидантний потенціал похідних 3-оксипіридину за умов хронічної гіпоксичної гіпоксії / С. П. Пасевич, І. І. Заморський // Укр. біофармац. журн. – 2014. – № 5. – С. 9-12.

Камышников, В. С. Справочник по клинико-биохимическим исследованиям и лабораторной диагностике / В. С. Камышников. – М.: МЕДпресс-информ, 2009. – 896 с.

Методы биохимических исследований (липидный и энергетический обмен) / под ред. М. И. Прохоровой. – Л.: Изд-во ЛГУ, 1982. – 272 с.






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