chiniofon and Hypersensitivity

In this study, we investigated the effect of 3,4,5-trihydroxy-N-(8-hydroxyquinolin-2-yl)benzamide) (SG-HQ2), a synthetic analogue of gallic acid (3,4,5-trihydroxybenzoic acid), on the mast cell-mediated allergic inflammation and the possible mechanism of action. Mast cells play major roles in immunoglobulin E-mediated allergic responses by the release of histamine, lipid-derived mediators, and pro-inflammatory cytokines. We previously reported the potential effects of gallic acid using allergic inflammation models. For incremental research, we synthesized the SG-HQ2 by the modification of functional groups from gallic acid. SG-HQ2 attenuated histamine release by the reduction of intracellular calcium in human mast cells and primary peritoneal mast cells. The inhibitory efficacy of SG-HQ2 was similar with gallic acid. Enhanced expression of pro-inflammatory cytokines such as tumor necrosis factor-α, interleukin-1β, interleukin-4, and interleukin-6 in activated mast cells was significantly diminished by SG-HQ2 100 times lower concentration of gallic acid. This inhibitory effect was mediated by the reduction of nuclear factor-κB. In animal models, SG-HQ2 inhibited compound 48/80-induced serum histamine release and immunoglobulin E-mediated local allergic reaction, passive cutaneous anaphylaxis. Our results indicate that SG-HQ2, an analogue of gallic acid, might be a possible therapeutic candidate for mast cell-mediated allergic inflammatory diseases through suppression of histamine release and pro-inflammatory cytokines.

Topics: Animals; Calcium; Cytokines; Gallic Acid; Histamine Release; Hydroxyquinolines; Hypersensitivity; Immunoglobulin E; Inflammation; Inflammation Mediators; Male; Mast Cells; Mice; NF-kappa B; Passive Cutaneous Anaphylaxis; Rats; Rats, Sprague-Dawley; Real-Time Polymerase Chain Reaction

Relaxant effects of the beta 2-selective adrenoceptor agonist TA-2005 on bronchoconstriction in the anesthetized guinea pig and cat were evaluated in comparison with other known beta 2-adrenoceptor agonists. The ED50 values of intravenously administered TA-2005, procaterol, formoterol, isoproterenol, salbutamol, and salmeterol to inhibit the histamine-induced bronchoconstriction of the guinea pigs were 0.024, 0.053, 0.056, 0.099, 0.23, and 2.00 micrograms/kg, respectively, and those in serotonin-challenged cats were 0.019, 0.037, 0.039, 0.042, 0.13, and 0.52 micrograms/kg, respectively, in the same increasing order. When guinea pigs were passively sensitized with anti-ovalbumin antiserum, the ED50 values of TA-2005, formoterol, procaterol, and isoproterenol to inhibit the antigen-induced bronchoconstriction were 0.09, 0.30, 0.65, and 7.0 micrograms/kg, i.v., respectively, while those of TA-2005, procaterol, formoterol, and salbutamol in actively sensitized animals were 0.24, 0.25, 1.40, and 23.0 micrograms/kg. When TA-2005 was administered by inhalation to guinea pigs or by the intraduodenal route to cats, it exhibited a long-lasting inhibitory effect comparable or superior to the effects of salmeterol and formoterol. These data indicate that, among the known beta 2-adrenoceptor agonists examined, TA-2005 exerts the most potent bronchodilating effects with a long duration of action in vivo, and its potency ratios to the other reference drugs were greater in antigen- than spasmogen-induced bronchoconstriction models.

Topics: Administration, Inhalation; Administration, Oral; Adrenergic beta-2 Receptor Agonists; Adrenergic beta-Agonists; Amphetamines; Animals; Bronchodilator Agents; Cats; Dose-Response Relationship, Drug; Female; Guinea Pigs; Histamine Antagonists; Hydroxyquinolines; Hypersensitivity; Injections, Intravenous; Male; Myocardial Contraction; Ovalbumin; Quinolones; Respiratory Function Tests; Serotonin

Topics: Bismuth; Cardiovascular Diseases; Diazepam; Drug Therapy; Endocrine System Diseases; Gastrointestinal Diseases; Glafenine; Hepatitis; Humans; Hydroxyquinolines; Hypersensitivity; Infections; Kidney Diseases; Metabolic Diseases; Neoplasms; Nervous System Diseases; Practolol; Respiratory Tract Diseases; Rheumatic Diseases

Topics: Allergens; Chlorhexidine; Ethylenediamines; Formaldehyde; Hexachlorophene; Humans; Hydroxyquinolines; Hypersensitivity; Intradermal Tests; Nickel; Parabens; Pharmaceutic Aids; Preservation, Biological; Preservatives, Pharmaceutical; Thimerosal; Vaccines

The synthesis and biological activity of a number of 4-hydroxy-3-nitro-2-quinolones are discussed and compared with their related hydroaromatic analogs. Antiallergic activity has been assessed by their ability to inhibit the homocytotropic antibody-antigen induced passive cutaneous anaphylaxis reaction in the rat.

Topics: Animals; Hydroxyquinolines; Hypersensitivity; Male; Nitroquinolines; Passive Cutaneous Anaphylaxis; Rats; Skin Tests

Topics: Dermatitis; Dermatitis, Contact; Humans; Hydroxyquinolines; Hypersensitivity; Immune System Diseases; Quinones