Ibuprofen protects rat livers from oxygen-derived free radical-mediated injury after tourniquet shock.
Rats subjected to tourniquet shock suffer a severe form of circulatory shock, tissue and organ oxidative stress, and final multiple system organ failure (MSOF) and death of the animals within 24 h of tourniquet release. The oxidative damage observed in hind-limb muscle tissue after reperfusion does not by itself account for the final systemic and lethal MSOF. We have postulated that organ failure has its genesis in a primary perfusion abnormality, e.g. the hind limbs, which is followed by secondary hypoperfusion of other organs, such as the liver, as has been shown to be the case in several septic shock models. It has also been shown that injured or necrotic tissue can activate neutrophils, Küpffer cells, platelets, and both the complement and coagulation cascades. In turn, complement activation also leads to neutrophil and Küpffer cell activation as assessed by their capacity to generate oxyradicals. Herein we have evaluated the potential protective effect of ibuprofen on hepatic oxygen-derived free radical production, as well as its effects on both polymorphonuclear leucocyte (PMN) activation and liver infiltration. The protective effect of ibuprofen on hepatic oxidative injury was assessed by determining total thiol groups (SH), thiobarbituric acid-reactive substances (TBARS), and by the release of aspartic acid (AsT) and alanine (AIT) aminotransferases in control animals, in animals subjected to 5 h of tourniquets, and in animals after 2 h of hind-limb reperfusion. Liver infiltration by PMNs was determined by histology after staining with eosin-hematoxylin, and PMN activation by their capacity to reduce nitro blue tetrazolium (NBT).(ABSTRACT TRUNCATED AT 250 WORDS)
Ward
P H
PH
Departamento de Fisiologia, Universidad de Concepción, Chile.
Maldonado
M
M
Roa
J
J
Manríquez
V
V
Vivaldi
E
E
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D056486:Chemical and Drug Induced Liver Injury; D005069:Evaluation Studies as Topic; D005609:Free Radicals; D007052:Ibuprofen / Q000627:therapeutic use*; D008107:Liver Diseases / Q000378:metabolism / Q000517:prevention & control*; D008297:Male; D018375:Neutrophil Activation / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015427:Reperfusion Injury / Q000150:complications / Q000378:metabolism / Q000517:prevention & control*; D012774:Shock, Traumatic / Q000150:complications / Q000378:metabolism*; D013438:Sulfhydryl Compounds / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D014111:Tourniquets
D005609:Free Radicals; D017382:Reactive Oxygen Species; D013438:Sulfhydryl Compounds; D017392:Thiobarbituric Acid Reactive Substances; D000410:Alanine Transaminase; D007052:Ibuprofen