ABSTRACT
Experiments were performed on glycerol-extracted muscle fibres prepared from psoas muscle of rabbit in the presence of hydroxyl free radical generating system. Short irradiation of spin-labelled muscle fibres by UV light showed the interaction of probe molecules with oxygen free radicals. The intensity of the EPR signal from maleimide or isothiocyanate spin labels attached to the essential thiol groups decreased following irradiation. Oxygen free radicals affected the rate constant of the transition AM.ADP.Vi-->AM.ADP in the ATP hydrolysis cycle. It was found that the essential -SH groups of myosin were involved in the oxidation of sulphydryls by Ce(IV). Ce(IV) complexed to nitrilotriacetic acid in the presence of spin trap produced long-lived free radicals located partly on SH-1 sulphydryls.
Subject(s)
Hydroxyl Radical/metabolism , Muscle Fibers, Skeletal/metabolism , Myosins/metabolism , Adenosine Diphosphate/metabolism , Adenosine Triphosphate/metabolism , Animals , Cesium/pharmacology , Cysteine/chemistry , Electron Spin Resonance Spectroscopy , Hydrolysis , In Vitro Techniques , Muscle Fibers, Skeletal/radiation effects , Myosins/chemistry , Myosins/radiation effects , Oxidants/pharmacology , Oxidation-Reduction , Psoas Muscles/metabolism , Psoas Muscles/radiation effects , Rabbits , Spin Labels , Sulfhydryl Compounds/metabolism , Ultraviolet Rays , Vanadates/pharmacologyABSTRACT
A 16-year-old boy undergone on an "anterior release" surgery for severe scoliosis, since fever developed in the postoperative phase, a total dose of 3500 mg paracetamol was given during a 3-day period. Four days after the end of antipyretic medication, the patient became confused and icteric, later unconscious, and within 24 hours died from fulminant hepatic failure. Autopsy revealed a confluent centrolobular (zonal 3) liver cell necrosis definitely characteristic for paracetamol hepatotoxicity. The case history may illustrate that paracetamol may cause liver injury even in therapeutic doses, if certain risk factors are present. Such factors are malnutrition and starvation, that causing depletion of hepatic glutathione, can result in enhanced susceptibility to toxicity of the drug. Authors emphasize, that in the case they presented, the young patient was malnourished and in the postoperative period fasting, and only a moderate calorie intake was given via parenteral nutrition. All these circumstances may well explain the unexpected fatal complication.
