Cutaneous Anaphylaxis In Rats Research Articles

Effects of Medium Molecular Weight Heparinyl Phenylalanine on Type I Hypersensitivity.

We investigated the inhibitory action of medium molecular weight heparinyl phenylalanine (MHF) on type I hypersensitivity in comparison with medium molecular weight heparinyl arginine (MHR). MHF and MHR were synthesized from heparin (HE) to decrease the side-effect of HE based on its anticoagulant action and used in this study. MHF demonstrated a significant inhibitory action on 48-h homologous passive cutaneous anaphylaxis in rats. Although MHF did not affect the death of mice injected with a lethal dose of histamine, it significantly prolonged the survival time of mice administered a lethal dose of compound 48/80. On the other hand, MHR did not inhibit type I hypersensitivity. The inhibitory action of MHF on the type I allergic reaction was due to a reduction or delay in histamine release from mast cells. MHF may be a potent anti-allergic agent.

Cornuside inhibits mast cell-mediated allergic response by down-regulating MAPK and NF-κB signaling pathways

AimsThe present study is to investigate the effect of cornuside on mast cell-mediated allergic response, as well as its possible mechanisms of action. MethodsTo test the anti-allergic effects of cornuside in vivo, local extravasation was induced by local injection of anti-dinitrophenyl immunoglobulin E (IgE) followed by intravenous antigenic challenge in passive cutaneous anaphylaxis model rats. Mast cell viability was determined using MTT assay. Histamine content from rat peritoneal mast cells was measured by the radioenzymatic method. To investigate the mechanisms by which cornuside affects the reduction of histamine release, the levels of calcium uptake were measured. To examine whether cornuside affects the expression of pro-inflammatory cytokines, Western blotting and ELISA were carried out. ResultsOral administration of cornuside inhibited passive cutaneous anaphylaxis in rats. Presence of cornuside attenuated IgE-induced histamine release from rat peritoneal mast cells. The inhibitory effect of cornuside on histamine release was mediated by the modulation of intracellular calcium. In addition, cornuside decreased phorbol 12-myristate 13-acetate (PMA) and calcium ionophore A23187-stimulated production and secretion of pro-inflammatory cytokines such as TNF-α and IL-6 in human mast cells. The inhibitory effect of cornuside on pro-inflammatory cytokines was dependent on nuclear factor-κB and p38 mitogen-activated protein kinase. ConclusionsThe present study provides evidence that cornuside inhibits mast cell-derived inflammatory allergic reactions by blocking histamine release and pro-inflammatory cytokine expression. Furthermore, in vivo and in vitro anti-allergic effects of cornuside suggest a possible therapeutic application of this agent in inflammatory allergic diseases.

Mast Cell Stabilizing, Antianaphylactic and Antihistaminic Activity of Coccinia grandis Fruits in Asthma

Coccinia grandis Linn (Curcubitaceae) is a climber herb cultivated throughout India. In traditional medicine fruits have been used to treat leprosy, fever, asthma, bronchitis and jaundice. In present study, ethanol extract of C. grandis fruit (ECGF) at 100, 125 and 150 mg·kg −1, i.p., was evaluated for mast cell stabilizing, antianaphylactic and antihistaminic activity using egg albumin induced mast cell degranulation in mice; passive cutaneous anaphylaxis in rats and clonidine induced catalepsy in mice respectively. ECGF at (100-150 mg·kg −1, i.p.) significantly protected egg albumin induced degranulations of mast cells and caused reduction of blue dye leakage in passive cutaneous anaphylaxis in dose dependently. The treatment ECGF also inhibited clonidine induced catalepsy in dose dependent manner. Phytochemical studies observed presence of saponin, steroids, alkaloids, flavonoids and glycosides. In conclusion ECGF possesses mast cell stabilizing; anti anaphylactic and antihistaminic potential which might be used in treatment of asthma.

Antiasthmatic activity of Ricinus communis L. roots

Objective To evaluate the antiasthmatic activity of Ricinus communis ( R. communis) Linn (Euphorbiaceae) to validate its traditional use. Methods The antiasthmatic activity of ethanol extract of R. communis (ERCR) root was evaluated on milk induced leucocytosis and eosinophilia in mice, mast cell degranulations in mice and passive cutaneous anaphylaxis in rats at (100-150 mg/kg). Results The ERCR significantly decreases milk induced leucocytosis and eosinophilia and protect degranulations of mast cells in mice. At the same dose ERCR inhibited passive cutaneous anaphylaxis in rats. Phytochemical study revealed the presence of steroids, saponin, alkaloids, flavonoids, and glycosides. Conclusions The flavonoids and saponins are reported to possess mast cell stabilizing and antianaphylactic activity. Hence ERCR shows antiasthmatic activity may be due to presence of flavonoids and/or saponins.

Evaluation of antiasthmatic activity of Clitoria ternatea L. roots

Clitoria ternatea L. (Family: Fabaceae) is being used in traditional medicine for the treatment of severe bronchitis and asthma. So the aim of study was to evaluate antiasthmatic activity of ethanol extract of Clitoria ternatea roots. In the present study ethanol extract of Clitoria ternatea root (ECTR) was evaluated for preliminary phytochemical screening, acute toxicity studies and antiasthmatic activity using milk induced leucocytosis and eosinophilia in mice, egg albumin induced mast cell degranulations in rats and passive cutaneous anaphylaxis in rats at doses (100-150 mg/kg ip). The results of present investigation showed that the LD(50) of ECTR is more than 1,300 mg/kg. ECTR significantly decreases milk induced leucocytosis and eosinophilia, protects egg albumin induced degranulations of mast cells in mice and inhibits area of blue dye leakage in passive cutaneous anaphylaxis in rats at (100-150 mg/kg, i.p.). Phytochemical studies observed the presence of steroids, saponin, flavonoids, and glycosides. The present investigation concludes that the antiasthmatic activity of ECTR may be due to the presence of flavonoids or saponins.

Mast cell stabilizing and antiallergic activity of Abrus precatorius in the management of asthma

Objective To investigate effects of ethanol extract of Abrus precatorius leaves (EAPL) on egg albumin induced mast cell degranulation in mice and passive cutaneous anaphylaxis in rats. Methods In present study ethanol extract of Abrus precatorius leaves (EAPL) at doses of 100, 125, 150 mg/kg i.p were evaluated for preliminary phytochemical screening, acute toxicity studies and egg albumin induced mast cell degranulation in mice and passive cutaneous anaphylaxis in rats. Results The results of present investigation showed that the LD 50 of EAPL is more than 1 300 mg/kg. EAPL (100-150 mg/kg, i.p.) significantly protect egg albumin induced degranulation of mast cell and inhibit area of leakage of dye in passive cutaneous anaphylaxis. Phytochemical studies observed presence of saponin, alkaloids, flavonoids, and glycosides. Conclusions In conclusion EAPL possesses anti asthmatic potential.

Inhibitory Effects of TJS-194 (Byakko-ka-keishi-to) on Rat OA-specific IgE Studied Reaction by Passive Cutaneous Anaphylaxis in Rats

Inhibitory Effects of TJS-194 (Byakko-ka-keishi-to) on Rat OA-specific IgE Studied Reaction by Passive Cutaneous Anaphylaxis in Rats

Pycnogenol® inhibits immunoglobulin E‐mediated allergic response in mast cells

IgE-dependent mast cell activation is known to be associated with the allergic diseases. Pycnogenol (PYC) is a standardized extract of the bark of French maritime pine containing bioflavonoids with a potent antioxidant activity. The antiallergic activity of PYC was evaluated using both in vivo and in vitro experimental models. Oral administration of PYC significantly inhibited anti-dinitrophenyl (DNP) IgE-mediated passive cutaneous anaphylaxis in rats. In an in vitro study, PYC dose-dependently reduced histamine release from rat peritoneal mast cells (RPMC) triggered by anti-DNP IgE. PYC inhibited the protein expression and secretion of tumor necrosis factor-alpha and interleukin-6 in anti-DNP IgE-stimulated RPMC. Moreover, PYC decreased anti-DNP IgE-induced calcium uptake into RPMC. Furthermore, PYC suppressed nuclear factor-kappa B activation. From these results, the clinical use of PYC in the mast cell-mediated immediate-type allergic diseases is proposed.

Anti-allergic effects of scoparone on mast cell-mediated allergy model

Scoparone is known to have a wide range of pharmacological properties in vitro. However, the roles of scoparone in immediate-type allergic reactions have not yet been investigated. In this study, we demonstrated that scoparone attenuated IgE-mediated allergic response in mast cells. Oral administration of scoparone inhibited passive cutaneous anaphylaxis in rats. Presence of scoparone dose-dependently decreased histamine release from rat peritoneal mast cells (RPMC) stimulated by anti-dinitrophenyl IgE. Moreover, scoparone reduced the expression and secretion of pro-inflammatory cytokines, such as tumor necrosis factor-alpha and interleukin-6 in RPMC. Pretreatment with scoparone inhibited the calcium uptake and p38 mitogen-activated protein kinase (MAPK) activity. Furthermore, scoparone blocked translocation of nuclear factor-kappa B (NF-kappaB) p65 subunit by suppressing IkappaBalpha phosphorylation in RPMC. Reduced calcium uptake as well as the suppressed activity of p38 MAPK and NF-kappaB might be involved in the inhibitory effect of scoparone on the secretory response. Our findings suggest that scoparone may serve as an effective therapeutic agent for allergic diseases.

Anti-Inflammatory Activity of the Ethanol Extract of Chungkukjang, Korean Fermented Bean: 5-Lipoxygenase Inhibition

The anti-inflammatory activity of Chungkukjang, a Korean traditional fermented soybean food (Korean-style Natto), was examined for the first time. From the results, it was found that the ethanol extract of Chungkukjang inhibited 5-lipoxygenase from A23187-treated RBL-1 cells, reducing leukoriene production (50% inhibitory concentration = 54.1 microg/mL). However, it did not greatly affect cyclooxygenase-2-catalyzed prostaglandin E(2) and inducible nitric oxide synthase-catalyzed nitric oxide production from lipopolysaccharide-treated RAW 264.7 cells at the same concentration ranges. Since leukotrienes are intimately involved in some allergic disorders, the anti-allergic activity of Chungkukjang was further examined in animal models of passive cutaneous anaphylaxis (type I hypersensitivity) and arachidonic acid-induced ear edema, two well-known in vivo models sensitive to 5-lipoxygenase inhibitors. After oral administration for 5 consecutive days, Chungkukjang significantly reduced (27.3%) passive cutaneous anaphylaxis in rats at 400 mg/kg/day. It also showed in vivo anti-inflammatory activity against arachidonic acid-induced mouse ear edema. Therefore, it is suggested that Chungkukjang may be beneficial for several allergic conditions such as asthma and atopic dermatitis.

Biphasic response of cutaneous blood flow induced by passive cutaneous anaphylaxis in rats

In the immediate phase of passive cutaneous anaphylaxis, sensitized skin mast cells release various mediators when activated by antigen. The present study investigated the effects of the mediators on cutaneous blood flow at the antigen–antibody reaction site. Induction of passive cutaneous anaphylaxis produced a biphasic response consisting of an initial decrease, followed by a sustained increase, in the cutaneous blood flow. The initial phase was almost eliminated by the 5-hydroxytryptamine receptor antagonist methysergide, whereas the second phase was sensitive to the histamine H 2 receptor antagonist ranitidine. The histamine H 1 receptor antagonist chlorpheniramine, the denervation of sensory nerves with capsaicin, the cyclooxygenase inhibitor indomethacin, or the bradykinin B 2 receptor antagonist d-arginyl- l-arginyl- l-prolyl-trans-4-hydroxy- l-prolylglycyl-3-(2-thienyl)- l-alanyl- l-seryl- d-1,2,3,4-tetrahydro-3-isoquinolinecarbonyl- l-(2α,3β,7aβ)-octahydro-1 H-indole-2-carbonyl- l-arginine (HOE140) did not affect the blood-flow changes caused by the anaphylaxis. These results suggest that 5-hydroxytryptamine and histamine H 2 receptors mediate the initial decrease and the subsequent increase in cutaneous blood flow, respectively, induced by passive cutaneous anaphylaxis in rats.

Antiallergic and anti-inflammatory properties of the ethanolic extract from Gleditsia sinensis.

This study was carried out to determine the effects of the 70% ethanolic extract from the anomalous fruits of Gleditsia sinensis LAM. (AFGS) on experimental allergic reactions and inflammation. AFGS (200, 500, 1000 mg/kg, p.o.) dose-dependently inhibited the systemic anaphylactic shock induced by compound 48/80 in mice and cutaneous reactions induced by histamine or serotonin in rats. At doses of 500 and 1000 mg/kg, AFGS showed a clear inhibition on homologous passive cutaneous anaphylaxis in rats. In vitro, AFGS significantly reduced histamine release from rat peritoneal mast cells triggered by compound 48/80 at concentrations of 20 and 50 micro/ml. Moreover, AFGS (500, 1000 mg/kg, p.o.) showed a significant inhibition on the hind paw edema in rats and ear swelling in mice caused by carrageenin and croton oil, respectively. It also clearly inhibited the vascular permeability induced by acetic acid in mice at a dose of 1000 mg/kg. These findings demonstrate that the ethanolic extract from the anomalous fruits of Gleditsia sinensis possesses antiallergic and anti-inflammatory activities, which may be mediated by reducing the release of mediators such as histamine from mast cells and weakening the inflammatory action of these mediators.

Pharmacological, pharmacokinetic and clinical properties of olopatadine hydrochloride' (olopatadine), an antiallergic drug

Olopatadine is a selective histamine H1-receptor antagonist possessing inhibitory effects on the release of inflammatory lipid mediators such as leukotriene and thromboxane from human polymorphonuclear leukocytes and eosinophils. Olopatadine also inhibited the tachykininergic contraction in the guinea pig bronchi by prejunctional inhibition of peripheral sensory nerves. Oral administration of olopatadine inhibited passive cutaneous anaphylaxis in rats, experimental allergic rhinitis and bronchial asthmatic responses in actively sensitized guinea pigs. Olopatadine exerted no significant effects on action potential duration in isolated guinea pig myocardium and ventricular myocytes. Olopatadine was highly and rapidly absorbed in healthy volunteers. The urinary excretion of olopatadine accounted for not less than 58% and the contribution of metabolism was low in the elimination of olopatadine. Olopatadine was shown to be useful for the treatment of allergic rhinitis and chronic urticaria in double-blind clinical trials. Olopatadine was approved in Japan for the treatment of allergic rhinitis, chronic urticaria, eczema dermatitis, prurigo, pruritus cutaneous, psoriasis vulgaris and erythema exsudativum multiforme in December, 2000.

Role of Mast Cells in Antigen-Induced Airway Inflammation and Bronchial Hyperresponsiveness in Rats

The participation of mast cells in the induction of antigen-induced airway inflammation and bronchial hyperresponsiveness (BHR) to acetylcholine (ACh) was investigated using pharmacological agents and mast cell-deficient rats (Ws/Ws). A significant increase in the number of leukocytes in bronchoalveolar lavage fluid (BALF) and bronchial responsiveness to ACh were observed 24 h after antigen (ovalbumin) challenge in sensitized Brown-Norway (BN) rats. Disodium cromoglycate and terfenadine did not inhibit antigen-induced airway inflammation and BHR in sensitized BN rats. In contrast, cyclosporin A (CyA), FK-506 and prednisolone significantly inhibited antigen-induced airway inflammation and BHR in sensitized BN rats. In addition, disodium cromoglycate, terfenadine and prednisolone, but not CyA and FK-506, inhibited homologous passive cutaneous anaphylaxis in rats. Furthermore, a significant increase in the number of leukocytes in BALF and BHR was also observed in Ws/Ws rats 24 h after inhalation of antigen; however, the magnitude of BHR in Ws/Ws rats was lower than that in the congenic rats. These findings suggest that mast cells play a partial role in the development of antigen-induced BHR in rats and that the induction of BHR is barely suppressed by mast cell stabilizing agents.

Oral beta-stimulants can inhibit passive cutaneous anaphylaxis in rats through an indirect inhibitory mechanism: possible involvement of afferent and efferent nervous system via gastric beta2-adrenoceptor stimulation.

We previously demonstrated that oral l-ephedrine exerts an extremely rapid (within 20 s) inhibition of 48-h passive cutaneous anaphylaxis reaction (PCA) in rats by a possibly unidentified mode of action. In the present experiments, we elucidated the mechanism of the PCA inhibition by l-ephedrine using adrenoceptor agonists and antagonists. Rat antiserum was prepared with dinitrophenylated Ascaris suum extract + Bordetella pertussis. Passively skin-sensitised Wistar rats were mainly used. l-Ephedrine, and adrenoceptor agonists and antagonists were orally administered immediately before PCA provocation. Catecholamine depleting (6-hydroxydopamine, 6-OHDA), amine depleting (reserpine) or ganglion blocking (hexamethonium) agent was intraperitoneally or intravenously administered before the provocation. The effects of the drugs on PCA were assessed by inhibition of the dye leakage. beta-(propranolol) and beta2-(butoxamine) blocking agents reduced the inhibition of PCA by l-ephedrine, while the inhibition was not altered by either an a-blocking agent (phentolamine) or a beta1-(atenolol) selective antagonist. On the other hand, beta-(isoproterenol) and beta2-selective (salbutamol) agonists showed extremely rapid inhibition of PCA. However, the beta-selective agonist (dobutamine) had no effect on the reaction. The pretreatment with hexamethonium, reserpine or 6-OH-DA substantially attenuated the inhibitory effect of l-ephedrine on PCA. The results strongly suggest that beta2-adrenoceptors locate in the stomach and that their receptor excitement finally may lead to the inhibition of PCA via the stimulation of the central and peripheral nervous systems.

L-Ephedrine is a major constituent of Mao-Bushi-Saishin-To, one of the formulas of Chinese medicine, which shows immediate inhibition after oral administration of passive cutaneous anaphylaxis in rats.

Whether Mao-Bushi-Saishin-To (MBST), one of the formulas of classical Chinese medicine, is effective on 48-h passive cutaneous anaphylaxis (PCA) in rats and which substance in the formula is responsible for its inhibitory action were examined. In the studies on PCA, MBST (hot water extract of the whole herbal formula), extracts of Ephedra herb (Mao), l-ephedrine and other reference drugs were orally administered immediately or at various times before or 5 min after the antigen challenge. In the experiments on anaphylactic histamine release from rat peritoneal mast cells, l-ephedrine and d-pseudoephedrine were added at 10(-4)-10(-7) g/ml at 30, 10, 3 or 0 min before antigen provocation. The time course study indicated that MBST produced a prompt and long lasting inhibition of PCA. Among the constituents of Mao, l-ephedrine exerted this prompt inhibitory activity, but d-pseudoephedrine did not. Neither pseudoephedrine nor l-ephedrine prevented the anaphylactic histamine release from isolated peritoneal mast cells. It is strongly emphasised that the rapid suppression of PCA by orally administered l-ephedrine must be exerted by a mechanism distinct from that of suppression produced following gastrointestinal absorption of the drug, because the time required for the inhibition was extraordinarily short. However, direct inhibition of anaphylactic histamine release from isolated mast cells was excluded in this inhibition of PCA.

P–667 - Effects of stress on passive cutaneous anaphylaxis in rats and anaphylactic histamine release from the skin.

P–667 - Effects of stress on passive cutaneous anaphylaxis in rats and anaphylactic histamine release from the skin.

Pharmacological Studies on the Novel Antiallergic Drug HQL-79: I. Antiallergic and Antiasthmatic Effects in Various Experimental Models

The effects of oral administration of 4-benzhydryloxy-1-{3-(1H-tetrazol-5-yl)-propyl}piperidine (HQL-79), a newly synthesized antiallergic drug, in various experimental allergic and asthmatic models were investigated. HQL-79 markedly inhibited immediate hypersensitivity reactions such as passive cutaneous anaphylaxis in rats, antigen-induced bronchoconstriction and nasal vascular permeability in actively sensitized guinea pigs, like epinastine and ketotifen did. Airway eosinophilia in repeatedly antigen-exposed guinea pigs was suppressed by chronic administration of HQL-79 for 2 weeks. In another experiment, the antigen-induced late asthmatic response (LAR) in metyrapone-treated guinea pigs was also ameliorated by chronic treatment with HQL-79. Moreover, HQL-79 partially inhibited the toluene diisocyanate-induced delayed-type hypersensitivity (DTH) reaction in mice when administered chronically during the immunization period. The corticosteroid dexamethasone inhibited the airway inflammatory responses in guinea pigs and the DTH in mice. These results indicate that HQL-79 has potent inhibitory effects on the immediate hypersensitivity reactions, and when administered chronically, it also inhibits airway eosinophilia, LAR and DTH, similarly to corticosteroids.

Effect of TYB-2285 on passive cutaneous anaphylaxis in rats

1. 1. TYB-2285 (1–30 mg/kg PO) inhibited ovalbumin (OA)- and dinitrophenyl- Ascaris (DNPAs)-induced passive cutaneous anaphylaxis (PCA) in a dose-dependent manner. 2. 2. The ED 50 of TYB-2285 and ketotifen fumarate on OA-induced PCA were 0.5 and 3.9 mg/kg, respectively. The ED 50 of TYP-2285 and amlexanox on DNP-As-induced PCA were 3.5 and 0.9mg/ kg, respectively. 3. 3. TYB-2285 (3–30 mg/kg PO) inhibited histamine consumption at the PCA site. 4. 4. Unlike cyproheptadine or amlexanox, TYB-2285 (30 mg/kg PO) did not inhibit histamine-, serotonin-, ascites-, 48/80-, or A23187-induced capillary permeability. It inhibited dextran-induced capillary permeability slightly. 5. 5. These results demonstrate that TYB-2285 inhibits PCA by inhibiting histamine release, although it does not inhibit capillary permeability.

Effects of siegesbeckia pubescens on immediate hypersensitivity reaction.

This study was carried out to examine the effect of an aqueous extract from Siegesbeckia pubescens (Compositae) (SPAE) on immunoglobulin E (IgE)-mediated immediate hypersensitivity reaction. Forty-eight hours passive cutaneous anaphylaxis in rats was significantly inhibited by oral administration of SPAE (100 micrograms/g). It also inhibited histamine release from rat peritoneal mast cells induced by anti-dinitrophenyl (DNP)-IgE and DNP-human serum albumin. The data indicate that SPAE has antiallergic activity, and that its action may be due to inhibition of histamine release from mast cells.