ABSTRACT
BACKGROUND: Reduced Glutathione (GSH) is a well known physiological antioxidant, that would protect against lethal effects of endotoxin. However, the site of the action of GSH can be intracellular (transmembrane passage of constitutive amino acids) or extracellular (membrane thiols). AIM OF THE WORK: To search if L-cysteine (one of three constitutive amino acids of GSH) protects against endotoxin as GSH and to search if inhibition of transmembrane passage of GSH and L-cysteine by Probenecid affects that protection. MATERIALS AND METHODS: Rats injected (n = 99) with a lethal dose of endotoxin (BACTO, DIFCO lab. 0111:B4 10 mg/kg ip) immediately after received: (a) Saline solution; (b) GSH 500 mg/kg; (c) L-Cysteine 0.25 g/kg; (d) Probenecid 25 mg/kg in 20% Ethanol plus GSH 500 mg/kg; (e) Probenecid 25 mg/kg in 20% Ethanol; (f) 20% Ethanol. The administration of Saline solution, GSH, L-cysteine was repeated two hours later. Injection volume was 0.5 ml ip. Survival rate of each group of rats was evaluated 6, 12 and 24 hours after endotoxin injection. Survival was compared with that of the control group by Fisher test. RESULTS: GSH and L-cysteine significantly increase survival if compared to all other treatments (respectively p < 0.002 and p < 0.001 at 12 hours; p < 0.005 and p < 0.0002 at 24 hours). Probenecid nullifies the survival increase caused by GSH. Probenecid alone or Ethanol alone show a survival rate not significantly different in respect to control group. CONCLUSIONS: Protection exerted by GSH against fatal effects of endotoxin is also provided by one of its constituent amino acids (L-cysteine) and is inhibited by Probenecid. So we can infer that such an antioxidant action happens at an intracellular site. Need of high doses of GSH and L-cysteine can be due to the necessity of a strong concentration gradient between extra and intracellular sites.
Subject(s)
Cysteine/therapeutic use , Glutathione/therapeutic use , Shock, Septic/drug therapy , Animals , Cysteine/pharmacology , Endotoxins/toxicity , Ethanol/therapeutic use , Glutathione/antagonists & inhibitors , Glutathione/pharmacology , Lipopolysaccharides/toxicity , Male , Oxidation-Reduction , Probenecid/therapeutic use , Rats , Rats, Wistar , Shock, Septic/chemically induced , Shock, Septic/metabolismABSTRACT
Oxygen-derived free radicals are naturally produced in biological systems mostly in ischemia and hypoxia related conditions. Imbalance of physiological defenses against oxygen-derived free radicals causes cellular damage. In our laboratory the role of oxygen radicals in the pathogenesis of circulatory shock was studied by exploiting the scavenging action of the spin-trapping compound phenyl-butyl-nitrone (PBN) in experiments concerning: (1) survival after shock, (2) microcirculatory derangements in endotoxin shock, (3) fluidity modifications of cell membranes during shock, (4) exhalation of ethane as non-invasive marker of shock. In some experiments the steroid methylprednisolone was used. Results showed that administration of PBN and of the steroid (1) ensures survival after otherwise lethal shock as confirmed by decreased ethane exhalation, (2) prevents microcirculatory troubles, (3) maintains stability of cell membranes. These findings strongly support the role of oxygen-derived free radicals in the pathogenesis and pathophysiology of circulatory shock.
Subject(s)
Oxygen/metabolism , Shock, Septic/physiopathology , Animals , Breath Tests , Cell Membrane/physiology , Cyclic N-Oxides , Ethane/analysis , Free Radicals , Male , Microsomes, Liver/physiology , Mitochondria/physiology , Nitrogen Oxides/pharmacology , Rats , Rats, Inbred Strains , Spin LabelsSubject(s)
Ethane/metabolism , Shock, Septic/metabolism , Shock, Traumatic/metabolism , Animals , Breath Tests , Cyclic N-Oxides , Ethane/analysis , Free Radicals , Lipid Peroxides/metabolism , Male , Methylprednisolone/pharmacology , Nitrogen Oxides/pharmacology , Oxygen/metabolism , Rats , Rats, Inbred StrainsSubject(s)
Nitrogen Oxides/therapeutic use , Oxygen/metabolism , Shock/drug therapy , Animals , Cell Membrane/drug effects , Cyclic N-Oxides , Electron Spin Resonance Spectroscopy , Free Radicals , Male , Methylprednisolone/therapeutic use , Rats , Rats, Inbred Strains , Shock/metabolism , Shock, Traumatic/drug therapyABSTRACT
Oxygen free-radicals appear to be involved in the pathogenesis of shock; therefore trapping of these radicals would modify the evolution of experimental shock. Experiments were performed on rats submitted to 100% lethal whole body trauma (rotating drum) and their survival, pathology, acid-base status and hematocrit level observed. The spin trapping agent phenyl-t-butyl-nitrone (PBN) was administered before trauma (50, 100, 150 mg/kg i.p.) or at various intervals (30, 60 minutes) after establishment of a severe traumatic shock. It appeared that PBN administration was highly effective both in prevention and in reversion of traumatic shock in rats.
Subject(s)
Nitrogen Oxides/therapeutic use , Shock, Traumatic/drug therapy , Shock, Traumatic/prevention & control , Animals , Cyclic N-Oxides , Free Radicals , RatsABSTRACT
Se presentan 31 pacientes tratados por traumatismos toracicos graves en el periodo 1978-1982. Se realizan consideraciones sobre la forma de produccion, lesiones, evolucion y causas de muerte. Asimismo se define la forma de diagnostico y tratamiento de un equipo de trabajo en particular
Subject(s)
Humans , Wounds, Nonpenetrating , Thoracic InjuriesABSTRACT
Se presentan 31 pacientes tratados por traumatismos toracicos graves en el periodo 1978-1982. Se realizan consideraciones sobre la forma de produccion, lesiones, evolucion y causas de muerte. Asimismo se define la forma de diagnostico y tratamiento de un equipo de trabajo en particular
