SCIENCE@home

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

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

Published 2023 in Scientific Reports

ABSTRACT

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 C_12TPP. 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.

PUBLICATION RECORD

CITATION MAP

EXTRACTION MAP

CLAIMS

  • No claims are published for this paper.

CONCEPTS

  • No concepts are published for this paper.

REFERENCES

Showing 1-90 of 90 references · Page 1 of 1

CITED BY

Showing 1-27 of 27 citing papers · Page 1 of 1