University of Oulu

Weidinger A, Birgisdóttir L, Schäffer J, Meszaros AT, Zavadskis S, Müllebner A, Hecker M, Duvigneau JC, Sommer N, Kozlov AV. Systemic Effects of mitoTEMPO upon Lipopolysaccharide Challenge Are Due to Its Antioxidant Part, While Local Effects in the Lung Are Due to Triphenylphosphonium. Antioxidants. 2022; 11(2):323.

Systemic effects of mitoTEMPO upon lipopolysaccharide challenge are due to its antioxidant part, while local effects in the lung are due to triphenylphosphonium

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Author: Weidinger, Adelheid1,2; Birgisdóttir, Linda1,2,3; Schäffer, Julia4;
Organizations: 1Ludwig Boltzmann Institute for Traumatology, The Research Center in Cooperation with AUVA, 1200 Vienna, Austria
2Austrian Cluster for Tissue Regeneration, 1200 Vienna, Austria
3Faculty of Biochemistry and Molecular Medicine, University of Oulu, 90570 Oulu, Finland
4Department of Internal Medicine, Universities of Giessen and Marburg Lung Center (UGMLC), Member of the German Center for Lung Research (DZL), Excellence Cluster Cardio-Pulmonary Institute (CPI), Justus-Liebig University, 35392 Giessen, Germany
5Department of Visceral, Transplant and Thoracic Surgery, Medical University of Innsbruck, 6020 Innsbruck, Austria
6Department for Biomedical Sciences, Institute for Medical Biochemistry, University of Veterinary Medicine, 1210 Vienna, Austria
7Laboratory of Navigational Redox Lipidomics, Department of Human Pathology, IM Seche-Nov Moscow State Medical University, 119146 Moscow, Russia
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 3.3 MB)
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Language: English
Published: Multidisciplinary Digital Publishing Institute, 2022
Publish Date: 2022-05-18


Mitochondria-targeted antioxidants (mtAOX) are a promising treatment strategy against reactive oxygen species-induced damage. Reports about harmful effects of mtAOX lead to the question of whether these could be caused by the carrier molecule triphenylphosphonium (TPP). The aim of this study was to investigate the biological effects of the mtAOX mitoTEMPO, and TPP in a rat model of systemic inflammatory response. The inflammatory response was induced by lipopolysaccharide (LPS) injection. We show that mitoTEMPO reduced expression of inducible nitric oxide synthase in the liver, lowered blood levels of tissue damage markers such as liver damage markers (aspartate aminotransferase and alanine aminotransferase), kidney damage markers (urea and creatinine), and the general organ damage marker, lactate dehydrogenase. In contrast, TPP slightly, but not significantly, increased the LPS-induced effects. Surprisingly, both mitoTEMPO and TPP reduced the wet/dry ratio in the lung after 24 h. In the isolated lung, both substances enhanced the increase in pulmonary arterial pressure induced by LPS observed within 3 h after LPS treatments but did not affect edema formation at this time. Our data suggest that beneficial effects of mitoTEMPO in organs are due to its antioxidant moiety (TEMPO), except for the lung where its effects are mediated by TPP.

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Series: Antioxidants
ISSN: 2076-3921
ISSN-E: 2076-3921
ISSN-L: 2076-3921
Volume: 11
Issue: 2
Article number: 323
DOI: 10.3390/antiox11020323
Type of Publication: A1 Journal article – refereed
Field of Science: 1182 Biochemistry, cell and molecular biology
Funding: This work was supported by Österreichische Forschungsförderungsgesellschaft mbH (FFG) Projekt number FO999887791 and by Deutsche Forschungsgemeinschaft (DFG, German Research Foundation)—Project number 268555672—SFB 1213, Project A06.
Copyright information: © 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (