tranilast and Anaphylaxis

Zhengqing Fengtongning (ZQFTN), the pharmaceutical preparation of sinomenine (SIN) derived from the medicinal plant Sinmenium acutum, is well-known in China as an effective treatment for rheumatoid arthritis (RA). However, its histamine-release anaphylactoid reactions (HRARs) occur often in some patients. Therefore, it is desirable to establish effective clinical protocols to manage such HRARs. In the study, rat models with systemic HRARs and local HRARs of the skin were established. The level of vascular permeability and mast cell numbers was determined by quantitative analysis using Evans blue dye and histological assays. The levels of histamine, leukotriene B4 (LTB4) and IL-33 in plasma were detected by UHPLC-SPE-MS, ELISA and immunohistochemistry assays, respectively. The results demonstrated that SIN significantly induced both systemic and local HRARs in rats, showing significant decrease of body temperature, increases in vascular permeability in skin, injury of lung tissues and mast cell infiltration and IL-33 expression in skin and lung tissues. Mechanistic study showed that tranilast could prevent SIN-triggered HRARs via inhibition of H1 receptor gene expression and NF-κB signaling. Our findings provide evidence that mast cell membrane stabilizers and H1 receptor blockers effectively prevent SIN-induced HRARs, and cromolyn, cetirizine and tranilast can be used in the clinic for the management of HRARs induced by ZQFTN.

Topics: Acute Lung Injury; Anaphylaxis; Animals; Anti-Allergic Agents; Cetirizine; Cromolyn Sodium; Female; Histamine; Histamine H1 Antagonists; Histamine Release; Interleukin-33; Leukotriene B4; Lung; Mast Cells; Morphinans; NF-kappa B; ortho-Aminobenzoates; Rats, Sprague-Dawley; Receptors, Histamine H1; Signal Transduction; Skin

The effects of some antiallergic agents on passive air-pouch anaphylaxis (PAPA) in the dorsal skin of rats were investigated by measuring plasma exudation and histamine content in the pouch fluid. Antiallergic agents, disodium cromoglycate (DSCG), tranilast and ketotifen, dose dependently inhibited both plasma exudation and histamine release, except that ketotifen showed a dose-unrelated inhibition of histamine release. An antihistamine, pyrilamine, suppressed plasma exudation without affecting histamine release. A cyclooxygenase inhibitor, indomethacin, and a 5-lipoxygenase inhibitor, nordihydroguaiaretic acid (NDGA), showed no significant effect. A slow-reacting substance of anaphylaxis antagonist, FPL55712, exerted no effect at 0.3 and 3.0 micrograms/ml, but at 50 micrograms/ml it suppressed not only plasma exudation but also histamine release. Dexamethasone suppressed plasma exudation dose dependently without inhibiting histamine release significantly. A beta-stimulant, isoproterenol, and prostaglandin E2 also exerted significant inhibitory effects on plasma exudation but not on histamine release at 1 mg/ml. Theophylline inhibited both plasma exudation and histamine release. These observations indicate that PAPA is useful for studying antiallergic agents.

Topics: Adult; Air; Anaphylaxis; Animals; Capillary Permeability; Chromones; Cromolyn Sodium; Dexamethasone; Dinoprostone; Exudates and Transudates; Histamine Release; Humans; Immunization, Passive; Indomethacin; Isoproterenol; Ketotifen; Masoprocol; Models, Biological; ortho-Aminobenzoates; Pyrilamine; Rats; Rats, Inbred Strains; Theophylline

Effects of antiallergic agents on 2,4-dinitrophenylated Ascaris extract (DNP-As)-induced bronchial asthma were studied in Lewis rats, and compared with those on passive cutaneous anaphylaxis (PCA). Effects of methysergide and chlorpheniramine on the bronchial asthma model were also investigated. Rats were actively sensitized with DNP-As antigen and with killed Bordetella pertussis. After 8 d, asthmatic response was provoked by inhalation of DNP-As. The bronchomotor response was measured with a modified Konzett-Rössler method in diaphragm-sectioned rats. The inhalation of DNP-As caused a marked asthmatic bronchoconstriction without significant effect on systemic blood pressure and heart rate. Disodium cromoglycate (DSCG), 10 mg/kg, i.v., trans-4-guanidinomethylcyclohexanecarboxylic acid p-tert-butylphenyl ester hydrochloride (NCO-650) and tranilast at doses of 30 and 100 mg/kg, intraduodenally, significantly inhibited the asthmatic response. Chlorpheniramine and methysergide at a dose of 1 mg/kg, i.v. also significantly inhibited it. The above doses of NCO-650 and tranilast significantly inhibited 48 h PCA, while DSCG almost abolished the PCA. These results indicate that 1) NCO-650 and tranilast inhibited both the asthmatic response and PCA in almost the same degree, 2) DSCG inhibited PCA much more strongly than asthmatic response, and 3) histamine and 5-hydroxytryptamine may be involved in this asthmatic response.

Topics: Anaphylaxis; Animals; Asthma; Chlorpheniramine; Cromolyn Sodium; Cyclohexanecarboxylic Acids; Disease Models, Animal; Histamine H1 Antagonists; Methysergide; ortho-Aminobenzoates; Passive Cutaneous Anaphylaxis; Rats; Rats, Inbred Lew; Ventilation-Perfusion Ratio

Topics: Anaphylaxis; Animals; Drug Synergism; Drug Therapy, Combination; Guinea Pigs; Male; Nifedipine; ortho-Aminobenzoates; SRS-A

Effects of chlorpheniramine and two antiallergic drugs on the active cutaneous anaphylaxis (ACA) reaction induced by intradermal injection of Ascaris suum antigen in naturally sensitized dogs were investigated. Chlorpheniramine (10 mg/kg, intraduodenally (i.d.)) almost abolished the ACA reaction. NCO-650 (100 mg/kg, i.d.) had no inhibitory effect, while tranilast (300 mg/kg, i.d.) showed a weak inhibitory effect. These findings show that the ACA reaction is almost totally mediated by histamine and ACA reaction is considerably resistant to antiallergic drugs such as tranilast and NCO-650.

Topics: Anaphylaxis; Animals; Antigens, Helminth; Ascaris; Chlorpheniramine; Cyclohexanecarboxylic Acids; Dogs; Dose-Response Relationship, Drug; Histamine; Intradermal Tests; Male; ortho-Aminobenzoates; Skin; Skin Tests

Topics: Acetylcholine; Anaphylaxis; Animals; Female; Guinea Pigs; Histamine Antagonists; Ketotifen; Medicine, Chinese Traditional; Medicine, East Asian Traditional; ortho-Aminobenzoates; Passive Cutaneous Anaphylaxis; Plant Extracts