Titel (eng)

Systemic Effects of mitoTEMPO upon Lipopolysaccharide Challenge Are Due to Its Antioxidant Part, While Local Effects in the Lung Are Due to Triphenylphosphonium

Autor*in

Adelheid Weidinger   Ludwig Boltzmann Institute for Traumatology

Andrey V. Kozlov   Ludwig Boltzmann Institute for Traumatology / Moscow State Medical University

Natascha Sommer   Justus-Liebig University

Johanna Catharina Duvigneau   University of Veterinary Medicine Vienna

Matthias Hecker   Justus-Liebig University

Andrea Müllebner   University of Veterinary Medicine Vienna

Sergejs Zavadskis   Ludwig Boltzmann Institute for Traumatology

Andras T. Meszaros   Medical University of Innsbruck

Linda Birgisdóttir   Ludwig Boltzmann Institute for Traumatology / Austrian Cluster for Tissue Regeneration / University of Oulu

Julia Schäffer   Justus-Liebig University

Verlag

MDPI

Beschreibung (eng)

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.

Sprache des Objekts

Englisch

Datum

2022

Rechte

Dieses Werk bzw. dieser Inhalt steht unter einer
CC BY 4.0 - Creative Commons Namensnennung 4.0 International Lizenz.

CC BY 4.0 International

http://creativecommons.org/licenses/by/4.0/

Klassifikation

Reactive Oxygen; Hydrogen-Peroxide; Pulmonary Inflammation; Oxidative Stress; Edema; Mitochondria; Dysfunction; Sepsis; Injury; Liver

Mitglied in der/den Collection(s) (1)