salicylates and Shock--Septic

Reactive oxygen species contribute to the multiple organ failure endotoxic shock. Here we investigate the effects of a salen-manganese complex, which exhibits both superoxide dismutase and catalase activity (EUK-134), on the circulatory failure and the renal and liver injury and dysfunction caused by endotoxin in the anaesthetised (thiopentone, 120 mg/kg) rat.. Male Wistar rats were anaesthetised with thiopentone sodium (120 mg/kg i.p.) and instrumented for the measurements of systemic haemodynamics. Animals received lipopolysaccharide (LPS, E. coli, 6 mg/kg i.v.) or saline and were treated with either EUK-134 (0.3 or 1 mg/kg bolus injection followed by an infusion of 0.3 or 1 mg/kg/h) or its vehicle (saline). After 6 h of endotoxaemia, blood was taken to evaluate biochemical parameters of organ injury and dysfunction. All data are mean I s.e. mean of n observations. Statistical comparisons were made with a ANOVA followed by Dunnet's test for multiple comparisons.. Endotoxaemia for 6 h caused hypotension, renal dysfunction, liver injury, skeletal-muscle injury and pancreatic injury. Treatment of rats with EUK-134 attenuated the renal dysfunction as well as the liver and skeletal muscle injury (but not the pancreatic injury) caused by endotoxin.. Thus, an enhanced formation of reactive oxygen species importantly contribute to the organ injury and dysfunction associated with endotoxic shock. We propose that small molecules, which have the catalytic activity of both superoxide dismutase and catalase, may represent a novel therapeutic approach for the therapy of endotoxic shock.

Topics: Animals; Endotoxins; Hypotension; Kidney; Liver; Male; Manganese Compounds; Muscle, Skeletal; Organometallic Compounds; Pancreas; Rats; Rats, Wistar; Reactive Oxygen Species; Salicylates; Shock, Septic; Superoxide Dismutase; Time Factors

Topics: Diagnosis, Differential; Humans; Male; Middle Aged; Salicylates; Salicylic Acid; Shock, Septic

Effects of choline salicylate, sodium salicylate, choline chloride and acetylsalicylic acid on platelet aggregation in vivo, ex vivo and in vitro in mice were studied. These drugs all inhibited adenosine diphosphate (ADP)-induced respiratory depression, which is closely related to platelet aggregation in vivo, with choline salicylate showing the strongest inhibitory effect. Choline salicylate had a tendency to reduce the mortality of animals injected intravenously with endotoxin, but the other drugs had no such effect. The inhibitory effects of these drugs on ADP-induced platelet aggregation ex vivo were in the order of choline salicylate greater than acetylsalicylic acid congruent to sodium salicylate greater than choline chloride congruent to no effect, and plasma concentrations of protein-unbound salicylic acid at 1 hr after oral administration of drugs were in the order of choline salicylate greater than acetylsalicylic acid congruent to sodium salicylate. The in vitro effects of these drugs were in the order of choline salicylate congruent to sodium salicylate greater than choline chloride congruent to acetylsalicylic acid congruent to no effect. Therefore, it was considered that salicylic acid played an important role on the in vivo, ex vivo and in vitro effects of choline salicylate and that choline increased plasma concentrations of salicylic acid and consequently enhanced the in vivo and ex vivo effects of salicylic acid. Furthermore, the ex vivo effects of choline salicylate were found when ADP-induced platelet aggregation was measured with platelet-rich plasma prepared from blood collected with heparin as anti-coagulant, but not when blood was collected with citrate.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adenosine Diphosphate; Animals; Aspirin; Blood Platelets; Calcium; Choline; Drug Combinations; In Vitro Techniques; Male; Mice; Platelet Aggregation; Respiration; Salicylates; Shock, Septic; Sodium Salicylate

Topics: Barbiturates; Bemegride; Diuresis; Drug Evaluation; Humans; Parenteral Nutrition; Peritoneal Dialysis; Poisoning; Renal Dialysis; Salicylates; Shock, Septic

Topics: Adrenal Cortex Hormones; Animals; Haplorhini; Hemodynamics; Lung; Lung Diseases; Methylprednisolone; Pulmonary Circulation; Respiratory Function Tests; Salicylates; Shock; Shock, Hemorrhagic; Shock, Septic

Topics: Animals; Aspirin; Biological Assay; Blood Cell Count; Blood Platelets; Blood Pressure; Cats; Central Venous Pressure; Depression, Chemical; Dogs; Female; Half-Life; Male; Rats; Salicylates; Secretory Rate; Serotonin; Sheep; Shock, Septic; Stomach

Topics: Angioedema; Animals; Blood Coagulation Factors; Bradykinin; Carboxypeptidases; Carcinoid Tumor; Catecholamines; Chemical Phenomena; Chemistry; Colchicine; Complement System Proteins; Female; Glucocorticoids; Guinea Pigs; Haplorhini; Humans; Inflammation; Kallidin; Kallikreins; Kidney; Kinins; Muscle Contraction; Phenothiazines; Rats; Salicylates; Sheep; Shock, Septic; Stimulation, Chemical; Uterus; Vascular Diseases; Vascular Resistance; Vasodilator Agents

Topics: Animals; Blood Pressure; Capillaries; Capillary Permeability; Dogs; Endotoxins; Forelimb; Hematocrit; Perfusion; Regional Blood Flow; Salicylates; Shock, Septic