Soft tissue repair capacity after oxygen-derived free radical-induced damage in one hindlimb of the rat.
Oxygen-derived free radicals are suspected to play an important role in the pathogenesis of inflammation and ischemia/reperfusion of an extremity. In this study we investigated the repair capacity of a free radical-damaged hindlimb of the rat and the effect of the anti-oxidant N-acetyl-L-cysteine (NAC). In nonanesthetized rats (n = 39), the left hindlimb was continuously infused intra-arterially (1 ml/hr) for 24 hr with the free radical donor tert-butylhydroperoxide (tert-BuOOH, 25 mM). Subsequently the infusion system was disconnected and the repair of soft tissue damage was observed with special attention to various pain tests, vascular permeability ((99m)Tc-IgG scintigraphy), and histology for a maximum period of 6 weeks. In 12 of these tert-BuOOH-infused rats the antioxidant NAC was injected intraperitoneally. Six of the NAC-treated rats were killed after 24 hr of infusion, while the remaining 6 rats were disconnected, reinjected with NAC, and observed for 1 week. Tert-BuOOH infusion for 24 hr led to significantly increased pain sensations, vascular permeability, and histological damage. Treatment with NAC significantly reduced pain sensations and vascular permeability, though not to control levels. One week after disconnection, tissue damage was almost completely repaired in the NAC-treated rats. In the untreated rats, repair took longer but histology and vascular permeability were completely normalized within the observation period. Soft tissue damage, induced by 24-hr infusion of the free radical donor tert-BuOOH, showed spontaneous repair within 6 weeks. The antioxidant NAC significantly reduced the soft tissue damage and shortened the repair period.
van der Laan
L
L
Department of Surgery, University Hospital Nijmegen, The Netherlands.
Oyen
W J
WJ
Verhofstad
A A
AA
Tan
E C
EC
ter Laak
H J
HJ
Gabreels-Festen
A
A
Hendriks
T
T
Goris
R J
RJ
D000111:Acetylcysteine / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D003872:Dermatitis / Q000201:enzymology*; D005609:Free Radicals; D005979:Glutathione Peroxidase / Q000378:metabolism; D006614:Hindlimb; D006861:Hydrogen Peroxide / Q000378:metabolism; D007074:Immunoglobulin G; D008297:Male; D018482:Muscle, Skeletal / Q000098:blood supply / Q000378:metabolism / Q000473:pathology; D009220:Myositis / Q000201:enzymology*; D015609:Organotechnetium Compounds; D018384:Oxidative Stress / Q000502:physiology*; D010100:Oxygen / Q000378:metabolism; D010545:Peroxides / Q000494:pharmacology; D011877:Radionuclide Imaging; D051381:Rats; D017208:Rats, Wistar; D012881:Skin Temperature; D020122:tert-Butylhydroperoxide
D000975:Antioxidants; D005609:Free Radicals; D007074:Immunoglobulin G; D015609:Organotechnetium Compounds; D010545:Peroxides; C079358:technetium TC 99m polyclonal IgG; D020122:tert-Butylhydroperoxide; D006861:Hydrogen Peroxide; D005979:Glutathione Peroxidase; D010100:Oxygen; D000111:Acetylcysteine