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Antioxidant properties of a new pyridoxine derivative with NO-donating abilityстатья
Статья опубликована в высокорейтинговом журнале
Статья опубликована в журнале из списка Web of Science и/или Scopus- Авторы: Balakina Anastasia A., Prikhodchenko Tatyana R., Amozova Vera I., Mumyatova Victoria A., Stupina Tatyana S., Neganova Margarita E., Yakushev Ilya A., Kornev Alexey B., Gadomsky Svyatoslav Ya, Fedorov Boris S., Mishchenko Denis V.
- Журнал: Free Radical Biology and Medicine
- Том: 177
- Год издания: 2021
- Издательство: Elsevier BV
- Местоположение издательства: Netherlands
- Первая страница: S108
- Последняя страница: S109
- DOI: 10.1016/j.freeradbiomed.2021.08.164
- Аннотация: Cancer is one of the leading deaths causes in the world. Due to the use of anticancer drugs high doses, various side effects are often observed, including cardiotoxicity. The search for new drugs for adjuvant chemotherapy of tumors with low toxicity, antioxidant and NO-donor activity, and cardioprotective action is urgent. The aim of work was to study the cytotoxic, antioxidant and NO-donor properties of the hybrid compound B6NO (bis-(4,5-hydroxymethyl-2-methyl-3-hydroxy) pyridinium salt of 2-nitroxy-butane-1,4-diacid) for normal (Vero and FetMSC) and tumor cells (HeLa and HepG2). It was shown that B6NO exhibits antioxidant properties in the concentration range from 5 to 80 μM, while reducing the ROS content to the control level in normal cells during the oxidative stress induction by tert-butyl hydroperoxide. At the same time, the B6NO antioxidant activity on tumor cells was significantly lower. It was determined that B6NO chelates iron ions by 94%, while vitamin B6 in equimolar concentration bound ferrous ions by no more than 10% which indicates B6NO ability to block the Fenton reaction. In addition, it was revealed that the hybrid compound B6NO inhibits process of initiated lipid peroxidation more effectively than pyridoxine. When using the DAF-FM DA dye, it was determined that B6NO significantly increases the intracellular nitrogen monoxide accumulation in the normal cells, which is provided both by optimizing the nitrogen monoxide synthesis pathways via eNOS and by biotransformation of nitrate groups. The B6NO compound showed low toxicity, both in the cells and laboratory animal’s models. The B6NO increased or did not decrease doxorubicin and cisplatin cytotoxicity in experiments on tumor cells in vitro. Thus, the results indicate a high potential of the B6NO as a compound for tumors adjuvant chemotherapy. This work was supported by the Ministry of Education and Science of the Russian Federation, no. AAAA-A19-11092390041-5.
- Добавил в систему: Алдошин Сергей Михайлович