Intra-arterial tert-Butyl-hydroperoxide infusion induces an exacerbated sensory response in the rat hind limb and is associated with an impaired tissue oxygen uptake.
The objective of this study was to investigate oxidative stress and oxygen extraction mechanisms in an animal model of continuous intra-arterial infusion of a free radical donor and in an in vitro model using isolated mitochondria. tert-Butyl-hydroperoxide (tert-BuOOH, 25 mM) was infused for 24 h in the left hind limb of rats to induce soft tissue damage (n = 8). After 7 days, we assessed local sensory response, tissue oxygen consumption, oxygen radicals, and antioxidant levels. In vitro mitochondrial function was measured after stimulation of isolated mitochondria of skeletal muscle cells with increasing doses of tert-BuOOH. tert-BuOOH infusion resulted in an increased skin temperature (p = 0.04), impaired function, and a significantly increased pain sensation (p = 0.03). Venous oxygen saturation levels (p = 0.01) and the antioxidant ceruloplasmin (p = 0.04) were increased. tert-BuOOH inhibited mitochondrial function in vitro. Induction of free radical formation in the rat hind limb results in an exacerbated sensory response and is associated with impaired oxygen extraction, which likely results from mitochondrial dysfunction caused by free radicals.
Tan
Edward C T H
EC
690 Department of Surgery, Division of Trauma surgery, Radboud University Nijmegen Medical Centre, P.O. Box 9101, 6500 HB, Nijmegen, The Netherlands. E.Tan@chir.umcn.nl
van Goor
Harry
H
Bahrami
Soheyl
S
Kozlov
Andrey V
AV
Leixnering
Martin
M
Redl
Heinz
H
Goris
R Jan A
RJ
D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D002570:Ceruloplasmin / Q000032:analysis; D005978:Glutathione / Q000378:metabolism; D006614:Hindlimb; D007261:Infusions, Intra-Arterial; D008297:Male; D008931:Mitochondria, Muscle / Q000187:drug effects* / Q000378:metabolism; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects*; D010100:Oxygen / Q000097:blood*; D010101:Oxygen Consumption; D010146:Pain / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D026361:Reactive Nitrogen Species / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D012881:Skin Temperature / Q000187:drug effects; D017695:Soft Tissue Injuries / Q000378:metabolism* / Q000503:physiopathology; D020122:tert-Butylhydroperoxide / Q000008:administration & dosage / Q000494:pharmacology*
D000975:Antioxidants; D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species; D020122:tert-Butylhydroperoxide; D002570:Ceruloplasmin; D005978:Glutathione; D010100:Oxygen
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