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Mitochondria-Targeted Antioxidants SkQ1 and MitoTEMPO Failed to Exert a Long-Term Beneficial Effect in Murine Polymicrobial Sepsis
Joint Authors
Bauer, Michael
Skulachev, Vladimir P.
Szabó, Andrea
Rademann, Pia
Weidinger, Adelheid
Meszaros, Andras
Zipperle, Johannes
Jafarmadar, Mohammad
Dumitrescu, Sergiu
Hacobian, Ara
Ungelenk, Luisa
Röstel, Franziska
Weis, Sebastian
Kozlov, Andrey V.
Drechsler, Susanne
Osuchowski, Marcin F.
Bahrami, Soheyl
Kaszaki, Jozsef
Source
Oxidative Medicine and Cellular Longevity
Issue
Vol. 2017, Issue 2017 (31 Dec. 2017), pp.1-14, 14 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2017-09-19
Country of Publication
Egypt
No. of Pages
14
Main Subjects
Abstract EN
Mitochondrial-derived reactive oxygen species have been deemed an important contributor in sepsis pathogenesis.
We investigated whether two mitochondria-targeted antioxidants (mtAOX; SkQ1 and MitoTEMPO) improved long-term outcome, lessened inflammation, and improved organ homeostasis in polymicrobial murine sepsis.
3-month-old female CD-1 mice (n=90) underwent cecal ligation and puncture (CLP) and received SkQ1 (5 nmol/kg), MitoTEMPO (50 nmol/kg), or vehicle 5 times post-CLP.
Separately, 52 SkQ1-treated CLP mice were sacrificed at 24 h and 48 h for additional endpoints.
Neither MitoTEMPO nor SkQ1 exerted any protracted survival benefit.
Conversely, SkQ1 exacerbated 28-day mortality by 29%.
CLP induced release of 10 circulating cytokines, increased urea, ALT, and LDH, and decreased glucose but irrespectively of treatment.
Similar occurred for CLP-induced lymphopenia/neutrophilia and the NO blood release.
At 48 h post-CLP, dying mice had approximately 100-fold more CFUs in the spleen than survivors, but this was not SkQ1 related.
At 48 h, macrophage and granulocyte counts increased in the peritoneal lavage but irrespectively of SkQ1.
Similarly, hepatic mitophagy was not altered by SkQ1 at 24 h.
The absence of survival benefit of mtAOX may be due to the extended treatment and/or a relatively moderate-risk-of-death CLP cohort.
Long-term effect of mtAOX in abdominal sepsis appears different to sepsis/inflammation models arising from other body compartments.
American Psychological Association (APA)
Rademann, Pia& Weidinger, Adelheid& Drechsler, Susanne& Meszaros, Andras& Zipperle, Johannes& Jafarmadar, Mohammad…[et al.]. 2017. Mitochondria-Targeted Antioxidants SkQ1 and MitoTEMPO Failed to Exert a Long-Term Beneficial Effect in Murine Polymicrobial Sepsis. Oxidative Medicine and Cellular Longevity،Vol. 2017, no. 2017, pp.1-14.
https://search.emarefa.net/detail/BIM-1195240
Modern Language Association (MLA)
Rademann, Pia…[et al.]. Mitochondria-Targeted Antioxidants SkQ1 and MitoTEMPO Failed to Exert a Long-Term Beneficial Effect in Murine Polymicrobial Sepsis. Oxidative Medicine and Cellular Longevity No. 2017 (2017), pp.1-14.
https://search.emarefa.net/detail/BIM-1195240
American Medical Association (AMA)
Rademann, Pia& Weidinger, Adelheid& Drechsler, Susanne& Meszaros, Andras& Zipperle, Johannes& Jafarmadar, Mohammad…[et al.]. Mitochondria-Targeted Antioxidants SkQ1 and MitoTEMPO Failed to Exert a Long-Term Beneficial Effect in Murine Polymicrobial Sepsis. Oxidative Medicine and Cellular Longevity. 2017. Vol. 2017, no. 2017, pp.1-14.
https://search.emarefa.net/detail/BIM-1195240
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1195240