Oxandrolone protects against the development of multiorgan failure, modulates the systemic inflammatory response and promotes wound healing during burn injury

•This study examined the effect of oxandrolone in a mouse model of burn.•In some tissues MDA and MPO levels were lower in oxandrolone-treated mice.•Selected organ injury markers were lower in oxandrolone-treated mice.•Multiple inflammatory mediators were lower in oxandrolone-treated mice.•Oxandrolon...

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Bibliographic Details
Published in:Burns 2019-05, Vol.45 (3), p.671-681
Main Authors: Ahmad, Akbar, Herndon, David N., Szabo, Csaba
Format: Article
Language:English
Subjects:
Amylases - drug effects
Amylases - metabolism
Anabolic Agents - pharmacology
Anabolic steroids
Angiogenesis
Animals
Burns
Burns - immunology
Burns - metabolism
Burns - pathology
Cytokines - drug effects
Cytokines - immunology
Heart - drug effects
Inflammation
Kidney - drug effects
Kidney - metabolism
Liver - drug effects
Liver - metabolism
Lung - drug effects
Lung - metabolism
Malondialdehyde - metabolism
Mice
Myocardium - metabolism
Oxandrolone - pharmacology
Oxidative stress
Oxidative Stress - drug effects
Pancreas - drug effects
Pancreas - metabolism
Peroxidase - drug effects
Peroxidase - metabolism
Wound Healing - drug effects
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Summary:•This study examined the effect of oxandrolone in a mouse model of burn.•In some tissues MDA and MPO levels were lower in oxandrolone-treated mice.•Selected organ injury markers were lower in oxandrolone-treated mice.•Multiple inflammatory mediators were lower in oxandrolone-treated mice.•Oxandrolone accelerated the healing of the burn wound.•Thus, oxandrolone improves the outcome of burn injury in mice. Oxandrolone is a synthetic oral non-aromatizable testosterone derivative. This drug has been used successfully for several decades to safely treat growth delays in various diseases including Turner’s syndrome. Currently the use of oxandrolone is under clinical testing in children with burn injury; the available data indicate that the anabolic steroid increases net muscle protein balance, maintains lean body mass, and reduces intensive care unit stay. Although oxandrolone is already in clinical trials in burn patients, preclinical burn-related studies with oxandrolone – especially those that go beyond muscle-related parameters and focus on burn-associated organ dysfunction, inflammatory response and wound healing – remain to be conducted. In the current project, using a well-characterized murine model of third-degree burn, we have tested the effect of oxandrolone on indices of organ injury, clinical chemistry parameters and plasma levels of inflammatory mediators. In oxandrolone-treated mice (1mg/kg/day for up to 21 days) there was a significant amelioration of burn-induced accumulation of myeloperoxidase levels in heart and lung (but not the liver and kidney) and significantly lower degree of malon dialdehyde accumulation in the liver (but not the heart, lung and kidney). Oxandrolone-treated mice showed a significant attenuation of the burn-induced elevation in circulating alkaline aminotransferase and amylase levels, while blood urea nitrogen and creatinine levels remained unaffected, indicative of protective effects of the anabolic hormone against burn-induced hepatic and pancreatic (but not renal) functional impairment. Multiple burn-induced inflammatory mediators (TNF-α, IL-1α, IL-1β, IL-4, IL-6, IL-10, IL-12, IP-10, G-CSF, GM-CSF and interferon-γ) were significantly lower in the plasma of oxandrolone-treated animals after burn injury than in the plasma of controls subjected to burns. Finally, oxandrolone significantly accelerated burn wound healing. We conclude that oxandrolone improves organ function, modulates the systemic inflammatory response and
ISSN:0305-4179
1879-1409
DOI:10.1016/j.burns.2018.10.006