BGP-15 protects against oxaliplatin-induced skeletal myopathy and mitochondrial reactive oxygen species production in mice

Sorensen, James C, Petersen, Aaron C, Timpani, Cara A, Campelj, Dean G, Cook, Jordan, Trewin, Adam J, Stojanovska, Vanesa, Stewart, Mathew, Hayes, Alan and Rybalka, Emma 2017, BGP-15 protects against oxaliplatin-induced skeletal myopathy and mitochondrial reactive oxygen species production in mice, Frontiers in pharmacology, vol. 8, pp. 1-19, doi: 10.3389/fphar.2017.00137.

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Title BGP-15 protects against oxaliplatin-induced skeletal myopathy and mitochondrial reactive oxygen species production in mice
Author(s) Sorensen, James C
Petersen, Aaron C
Timpani, Cara A
Campelj, Dean G
Cook, Jordan
Trewin, Adam JORCID iD for Trewin, Adam J
Stojanovska, Vanesa
Stewart, Mathew
Hayes, Alan
Rybalka, Emma
Journal name Frontiers in pharmacology
Volume number 8
Article ID 137
Start page 1
End page 19
Total pages 19
Publisher Frontiers Media
Place of publication Lausanne, Switzerland
Publication date 2017-04
ISSN 1663-9812
Keyword(s) BGP-15
mitochondrial reactive oxygen species
muscle wasting
oxaliplatin chemotherapy
protein synthesis
skeletal muscle
Science & Technology
Life Sciences & Biomedicine
Pharmacology & Pharmacy
Summary Chemotherapy is a leading intervention against cancer. Albeit highly effective, chemotherapy has a multitude of deleterious side-effects including skeletal muscle wasting and fatigue, which considerably reduces patient quality of life and survivability. As such, a defense against chemotherapy-induced skeletal muscle dysfunction is required. Here we investigate the effects of oxaliplatin (OXA) treatment in mice on the skeletal muscle and mitochondria, and the capacity for the Poly ADP-ribose polymerase (PARP) inhibitor, BGP-15, to ameliorate any pathological side-effects induced by OXA. To do so, we investigated the effects of 2 weeks of OXA (3 mg/kg) treatment with and without BGP-15 (15 mg/kg). OXA induced a 15% (p < 0.05) reduction in lean tissue mass without significant changes in food consumption or energy expenditure. OXA treatment also altered the muscle architecture, increasing collagen deposition, neutral lipid and Ca2+ accumulation; all of which were ameliorated with BGP-15 adjunct therapy. Here, we are the first to show that OXA penetrates the mitochondria, and, as a possible consequence of this, increases mtROS production. These data correspond with reduced diameter of isolated FDB fibers and shift in the fiber size distribution frequency of TA to the left. There was a tendency for reduction in intramuscular protein content, albeit apparently not via Murf1 (atrophy)- or p62 (autophagy)- dependent pathways. BGP-15 adjunct therapy protected against increased ROS production and improved mitochondrial viability 4-fold and preserved fiber diameter and number. Our study highlights BGP-15 as a potential adjunct therapy to address chemotherapy-induced skeletal muscle and mitochondrial pathology.
Language eng
DOI 10.3389/fphar.2017.00137
Indigenous content off
Field of Research 1115 Pharmacology and Pharmaceutical Sciences
HERDC Research category C1 Refereed article in a scholarly journal
Copyright notice ©2017, Sorensen, Petersen, Timpani, Campelj, Cook, Trewin, Stojanovska, Stewart, Hayes and Rybalka
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Document type: Journal Article
Collections: Faculty of Health
Institute for Physical Activity and Nutrition
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