Mitochondria-Targeted Antioxidant SkQ1 Improves Muscle Contractility in Female C26 Tumor-Bearing Mice

• Published in: Physiology (Bethesda, Md.) Md.), 2023-05, Vol.38 (S1)
• Main Authors: Tsitkanou, Stavroula, Morena da Silva, Francielly, Cabrera, Regina, Schrems, Eleanor, Koopmans, Pieter, Khadgi, Sabin, Jones, Ronald, Lim, Seongkyun, Washington, Tyrone, Murach, Kevin, Greene, Nicholas
• Format: Article
• Language: English
• ISSN: 1548-9213; 1548-9221
• DOI: 10.1152/physiol.2023.38.S1.5733703

Abstract only Cancer cachexia (CC) affects up to 80% of cancer patients and is responsible for 20-40% of cancer related deaths. Our laboratory recently demonstrated that emission of muscle mitochondrial reactive oxygen species (ROS) is highly elevated shortly after the onset of tumor-bearing in mice. Therefore, targeting of mitochondrial ROS may be a viable option to treat and prevent CC. The aim of this study was to evaluate the effectiveness of a mitochondria-targeted antioxidant, SkQ1, at preventing CC. We hypothesized SkQ1 prevents muscle atrophy and weakness in tumor-bearing mice. To test the effect of SkQ1 on CC, female Balb/c mice were injected bilaterally with colon 26 adenocarcinoma (C26) cells to the hind flanks for a total cell volume of 1x106, while equal volume of PBS was injected in a separate cohort as a sham control. SkQ1 was dissolved in drinking water (250 nmol/kg body weight/day) and administered to mice, while control groups drank normal drinking water. Body weight was assessed every 5 days. In vivo muscle contractility and fatigability were assessed via electrophysiological measurements two days prior to endpoint. At the endpoint (~25 days after C26/PBS injections) body weight and tissue wet weights were measured and normalized by tibia length (mg/mm). Data were analyzed by 2X2 ANOVA with Tukey’s post hoc test where significant interactions were found with p≤0.05. C26 mice had lower tumor-free body weight (p