salicylates and Pleurisy

Topics: Adrenal Cortex Hormones; Arthritis; Electrocardiography; Humans; Inflammation; Morphine; Myocardial Infarction; Myositis; Pericarditis; Peritonitis; Pleurisy; Pneumonia; Salicylates

Topics: Acute Disease; Arthritis, Rheumatoid; Bone Diseases; Clinical Trials as Topic; Drug Synergism; Humans; Osteoarthritis; Osteochondritis; Osteoporosis; Pain; Penicillins; Placebos; Pleurisy; Prednisolone; Rheumatic Diseases; Rheumatic Fever; Salicylates; Spondylitis

Interaction between anti-inflammatory drugs and reactive oxygen metabolites must be considered in the course of pharmacological studies intended to develop new compounds. Effects of indomethacin, aspirin, and 3,5-diisopropylsalicylic acid (3,5-DIPS) and their copper complexes on PMNL oxidative metabolism and the evolution of an acute inflammatory reaction were studied in the rat. Experiments were performed in vitro by assessment of superoxide generation and reduction of chemiluminescence by PMNLs incubated or not (control) in medium containing various concentrations of these compounds. A dose-related decrease of these parameters was observed, however, copper complexes were found to be more effective than their parent drugs or Cu gluconate. Copper complexes were also more effective anti-inflammatory agents than their parent ligands or Cu gluconate when the volume of exudate and number of exudate PMNLs were assessed after induction of pleurisy in rats by injection of isologous serum. It is concluded that modulation of the PMNL oxidative burst by copper complexes offers an accounting for the anti-inflammatory activity of these compounds.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Copper; Free Radical Scavengers; In Vitro Techniques; Indomethacin; Luminescent Measurements; Male; Neutrophils; Oxidation-Reduction; Pleurisy; Rats; Rats, Inbred Strains; Salicylates; Superoxides

These studies were intended to compare the effects of aspirin, 3,5-diisopropysalicylic acid (3,5-DIPS), and indomethacin with those of their copper complexes: Cu(II)2(aspirinate)4, Cu(II)2(3,5-DIPS)4, and Cu(II)2(indomethacinate)4 as well as Cu(II)2(acetate)4 on polymorphonuclear leukocyte (PMNL) random and directional migration, in addition to their anti-inflammatory activities. Experiments were performed both in vivo and in vitro. In vitro modifications of PMNL migration were measured with the Boyden chamber using N-formyl-methionyl-leucyl-phenylalanine (fMLP) as the chemoattractant and in the agarose assay using fMLP and serum chemotactic derivatives of complement as chemoattractants. In vivo anti-inflammatory activities of these compounds were determined after induction of a serum-induced pleurisy in the rat, and measurement of exudate volume and number of exudative cells 4 hr later. Copper complexes of non-steroidal anti-inflammatory drugs (NSAIDs) were found to be more effective in decreasing random migration and chemotaxis of PMNLs than their parent drugs or Cu(II)2(acetate)4 in in vitro studies. Only chemotaxis was found to be reduced significantly for PMNLs obtained from pleuritic rats after in vivo treatment and the order of copper complex effectiveness was: Cu(II)2(indomethacinate)4 greater than Cu(II)2(3,5-DIPS)4 greater than Cu(II)2(aspirinate)4. All doses of Cu(II)2(acetate)4 administered in vivo failed to affect chemotactic activity. Copper complexes of NSAIDs were also more effective than their parent drugs as anti-inflammatory agents, and Cu(II)2(acetate)4 had no anti-inflammatory activity in this model of inflammation. The order of anti-inflammatory activity was: Cu(II)2(indomethacinate)4 greater than Cu(II)2(3,5-DIPS)4 greater than Cu(II)2(aspirinate)4.

Topics: Acetates; Acetic Acid; Animals; Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Cell Movement; Chemotaxis, Leukocyte; Indomethacin; Molecular Structure; Neutrophils; Organometallic Compounds; Pleurisy; Rats; Salicylates

A current hypothesis postulates that the antiinflammatory effect of aspirin (acetylsalicylic acid) is mediated by its metabolite salicylic acid through inhibition of PGE2 synthesis. We tested this hypothesis in rats with carrageenin-induced pleurisy. Aspirin or salicylate, given orally, reduced exudation and cell migration into the pleural cavity, aspirin being more potent than salicylate. The antiinflammatory effect of aspirin cannot be explained only in terms of salicylate formation. Doses of aspirin and salicylate that inhibit inflammation by 50% result in salicylate levels in the exudate of 70 +/- 12 and 323 +/- 17 micrograms/ml, respectively. At a significant antiinflammatory dose (100 mg/kg), salicylate did not reduce the prostaglandin and thromboxane content of the exudate. This indicates that inhibition of cyclooxygenase is not a likely mechanism for the antiinflammatory effect of salicylate. Salicylate only reduced the amount of 6-keto-PGF1 alpha in the exudate at higher doses (200 mg/kg), while aspirin at an equally antiinflammatory dose (50 mg/kg) reduced the content of 6-keto-PGF1 alpha, TXB2, PGD2 but not of PGE2 in the exudate. It therefore seems unlikely that an inhibition of PGE2 synthesis is the common mechanism by which aspirin and salicylate exert their antiinflammatory effects. These results do not supported the hypothesis that aspirin is a prodrug for salicylate but rather indicate that both compounds may exert their antiinflammatory effects partly by different mechanisms.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Blood Cell Count; Carrageenan; Gas Chromatography-Mass Spectrometry; Leukocytes; Pleurisy; Prodrugs; Prostaglandins; Rats; Salicylates

The penetration of the two components of imidazole 2-hydroxybenzoate (ITF 182), imidazole and salicylate, into inflamed sites induced by intrapleural injection of carrageenin in the rat and by a urate-cotton pellet implantation in the knee joint of the rabbit is studied. The results obtained show that the two components of the salt penetrate rapidly the inflamed sites and display different kinetic profiles: imidazole diffuses throughout inflamed and non-inflamed fluids without any specific localization, salicylate shows preferential localization in inflamed fluids and remains longer than imidazole.

Topics: Animals; Anti-Inflammatory Agents; Arthritis; Carrageenan; Exudates and Transudates; Imidazoles; Inflammation; Knee Joint; Male; Pleura; Pleurisy; Rabbits; Rats; Rats, Inbred Strains; Salicylates; Salicylic Acid; Synovial Membrane

Topics: Adolescent; Alanine Transaminase; Arthritis, Juvenile; Aspartate Aminotransferases; Bilirubin; Child; Child, Preschool; Clinical Enzyme Tests; Diagnosis, Differential; Female; Fever; Hepatomegaly; Humans; Infant; Leukocyte Count; Liver; Liver Function Tests; Lymphatic Diseases; Male; Pain; Pericarditis; Pleurisy; Salicylates; Sex Factors; Splenomegaly; Sulfobromophthalein

Topics: Anti-Allergic Agents; Blood Vessels; Capillary Permeability; Diaphragm; Histamine H1 Antagonists; Maleates; Permeability; Pharmacology; Pleurisy; Rats; Research; Salicylates; Turpentine; Veins

Topics: Pleurisy; Respiration Disorders; Salicylates; Sodium Salicylate