Mitochondrion-targeted antioxidant SkQ1 prevents rapid animal death caused by highly diverse shocks

Skulachev, V.; Vyssokikh, M.; Chernyak, B.; Averina, O.; Andreev-Andrievskiy, A.; Zinovkin, R.; Lyamzaev, K.; Marey, M.; Egorov, M.; Frolova, O.; Zorov, D.; Skulachev, M.; Sadovnichii, V.

Авторы: Skulachev VP, Vyssokikh MY, Chernyak BV, Averina OA, Andreev-Andrievskiy AA, Zinovkin RA, Lyamzaev KG, Marey MV, Egorov MV, Frolova OJ, Zorov DB, Skulachev MV, Sadovnichii VA
Журнал: Scientific reports
Том: 13
Номер: 1
Год издания: 2023
Издательство: Nature Publishing Group
Местоположение издательства: United Kingdom
Первая страница: 1
Последняя страница: 15
Номер статьи: 4326
DOI: 10.1038/s41598-023-31281-9
Аннотация: The response to stress involves the activation of pathways leading either to protection from the stress origin, eventually resulting in development of stress resistance, or activation of the rapid death of the organism. Here we hypothesize that mitochondrial reactive oxygen species (mtROS) play a key role in stress-induced programmed death of the organism, which we called “phenoptosis” in 1997. We demonstrate that the synthetic mitochondria-targeted antioxidant SkQ1 (which specifically abolishes mtROS) prevents rapid death of mice caused by four mechanistically very different shocks: (a) bacterial lipopolysaccharide (LPS) shock, (b) shock in response to intravenous mitochondrial injection, (c) cold shock, and (d) toxic shock caused by the penetrating cation C12TPP. Importantly, under all these stresses mortality was associated with a strong elevation of the levels of pro-inflammatory cytokines and administration of SkQ1 was able to switch off the cytokine storms. Since the main effect of SkQ1 is the neutralization of mtROS, this study provides evidence for the role of mtROS in the activation of innate immune responses mediating stress-induced death of the organism. We propose that SkQ1 may be used clinically to support patients in critical conditions, such as septic shock, extensive trauma, cooling, and severe infection by bacteria or viruses.
Добавил в систему: Лямзаев Константин Геннадьевич

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Mitochondrion-targeted antioxidant SkQ1 prevents rapid animal death caused by highly diverse shocksстатья

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