Systemic Effects of mitoTEMPO upon Lipopolysaccharide Challenge Are Due to Its Antioxidant Part, While Local Effects in the Lung Are Due to Triphenylphosphonium
Adelheid Weidinger,
Linda Birgisdóttir,
Julia Schäffer,
Andras T. Meszaros,
Sergejs Zavadskis,
Andrea Müllebner,
Matthias Hecker,
Johanna Catharina Duvigneau,
Natascha Sommer,
Andrey V. Kozlov
Affiliations
Adelheid Weidinger
Ludwig Boltzmann Institute for Traumatology, The Research Center in Cooperation with AUVA, 1200 Vienna, Austria
Linda Birgisdóttir
Ludwig Boltzmann Institute for Traumatology, The Research Center in Cooperation with AUVA, 1200 Vienna, Austria
Julia Schäffer
Department 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
Andras T. Meszaros
Department of Visceral, Transplant and Thoracic Surgery, Medical University of Innsbruck, 6020 Innsbruck, Austria
Sergejs Zavadskis
Ludwig Boltzmann Institute for Traumatology, The Research Center in Cooperation with AUVA, 1200 Vienna, Austria
Andrea Müllebner
Department for Biomedical Sciences, Institute for Medical Biochemistry, University of Veterinary Medicine, 1210 Vienna, Austria
Matthias Hecker
Department 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
Johanna Catharina Duvigneau
Department for Biomedical Sciences, Institute for Medical Biochemistry, University of Veterinary Medicine, 1210 Vienna, Austria
Natascha Sommer
Department 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
Andrey V. Kozlov
Ludwig Boltzmann Institute for Traumatology, The Research Center in Cooperation with AUVA, 1200 Vienna, Austria
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.