ovalbumin and Pruritus

The pathogenesis of allergic rhinitis (AR) is ambiguous, while it is clear that various immune cells and cytokines play crucial roles in its occurrence and development.. To investigate the effect of exogenous interleukin-10 (IL-10) on the expression of fibrinogen (FIB), procalcitonin (PCT), hypersensitive C-reactive protein (hs-CRP), and Th17/Treg-IL10/IL-17 axis balance in the nasal mucosa of rats with AR.. In this study, 48 female-specific pathogen-free Sprague-Dawley rats were randomly divided into 3 groups: blank control group, AR group, and IL-10 intervention group. The AR model was established in the AR group and IL-10 group. The rats in the control group were treated with normal saline; the rats in the AR group were given 20 μL of saline containing 50 μg of ovalbumin (OVA) every day. The rats in the IL-10 intervention group were intraperitoneally injected with 1 mL of 40 pg/kg IL-10 and provided with OVA. The IL-10 intervention group was composed of mice with AR that received IL-10. The behavior of nasal allergic symptoms (such as nasal itching, sneezing, and runny nose) and the hematoxylin and eosin staining of nasal mucosa were observed. The levels of FIB, PCT, hs-CRP, IgE, and OVA sIgE in serum were determined by enzyme-linked immunosorbent assay. The levels of Treg and Th17 cells in serum were detected by flow cytometry. The protein levels of TGF-β, IL-10, and IL-17 in nasal mucosa were detected by the Western-blot method.. The scores of snots, nasal itching, and sneezing in the AR group were significantly higher than those in the control group, while the scores of the above symptoms in the IL-10 intervention group were lower than those in the AR group. The levels of FIB, PCT, hs-CRP, IgE, and OVA sIgE in serum and the protein levels of IL-10 and IL-17 in the nasal mucosa in the AR group were higher than those in the blank control group. Meanwhile, the levels of FIB, PCT, hs-CRP, IgE, and OVA sIgE in serum and IL-10 and IL-17 protein in the nasal mucosa in the IL-10 group were lower than those in the AR group.. IL-10 can relieve the allergy of AR rats by affecting the expression of FIB, PCT, and hs-CRP, as well as the balance of the Th17/Treg-IL10/IL-17 axis in the nasal mucosa of AR rats.

Topics: Animals; C-Reactive Protein; Disease Models, Animal; Female; Fibrinogen; Hemostatics; Immunoglobulin E; Interleukin-10; Interleukin-17; Mice; Mice, Inbred BALB C; Nasal Mucosa; Ovalbumin; Procalcitonin; Pruritus; Rats; Rats, Sprague-Dawley; Rhinitis, Allergic; Sneezing; T-Lymphocytes, Regulatory; Th17 Cells

This study explored the curative effect of Jingfang Mixture on urticaria mice induced by aluminum hydroxide/ovalbumin, and discussed its mechanism. Sixty male Kunming mice were randomly divided into a normal group, a model group, three Jingfang Mixture(low-dose, medium-dose, and high-dose) groups, and a positive drug(cetirizine hydrochloride) group. The urticarial model in mice was induced by the intraperitoneal injection of the mixed solution of ovalbumin and aluminum hydroxide. The degrees of pruritus were observed after the second immunization. Pathological changes were detected by hematoxylin and eosin(HE) staining. Levels of interleukin 1β(IL-1β) and tumor necrosis factor α(TNF-α) in the serum were detected by enzyme linked immunosorbent assay(ELISA). Expressions of NOD-like receptor protein 3(NLRP3) and IL-1β were detected by immunohistochemistry(IHC). Expressions of nuclear factor kappa-B(NF-κB p65), NLRP3, apoptosis-associated speck-like protein containing a CARD(ASC), cysteinyl aspartate-specific proteases 1(caspase-1), and IL-1β proteins were detected by Western blot. The results showed that, except for the normal group, the mice in all groups had different degrees of pruritus. Compared with the model group, the Jingfang Mixture groups and the positive drug group prolonged the scratching latency of mice(P<0.05), and significantly reduced the number of scratching(P<0.05). In addition, the Jingfang Mixture groups and the positive drug group improved the pathological morphology of skin tissue. The expression levels of IL-1β and TNF-α in serum were significantly reduced(P<0.05), and the number of NLRP3 and IL-1β positive cells was decreased(P<0.01). The expressions of p-NF-κB p65, NLRP3, ASC, cleaved caspase-1, and IL-1β protein were significantly down-regulated(P<0.05). The results of the above study indicate that Jingfang Mixture inhibit the inflammatory response in urticaria mice, and the mechanism may be related to the inhibition of activating NF-κB/NLRP3/IL-1β signaling pathway.

Topics: Aluminum Hydroxide; Animals; Caspase 1; Interleukin-1beta; Male; Mice; NF-kappa B; NLR Family, Pyrin Domain-Containing 3 Protein; Ovalbumin; Pruritus; Signal Transduction; Tumor Necrosis Factor-alpha; Urticaria

Skin thermal changes modulate itch sensitivity. However, the mechanisms of this modulation are still unclear. Using mouse models of acute and chronic itch, we investigated whether local innocuous thermal stimulation of the skin alters itch sensitivity and if blockade of thermosensitive transient receptor potential (TRP) channels can reduce these changes. Localized thermal changes were achieved by placing a thermal probe in contact with the back skin for 30 s. Warming the skin significantly increased serotonin-evoked scratching and spontaneous scratching in the ovalbumin model of atopic dermatitis but decreased histamine-evoked scratching. These changes were blocked by a TRPV4 antagonist. Cooling the skin significantly increased serotonin-evoked scratching but reduced histamine-evoked scratching. The increase in serotonin-evoked scratching, but not the reduction of histamine-evoked scratching, was blocked by TRPM8 antagonism. Chloroquine-evoked scratching was unaffected by either warming or cooling. Our data indicate that different itch signaling pathways are differentially modulated by skin thermal changes.

Topics: Animals; Antipruritics; Body Temperature Regulation; Dermatitis, Atopic; Disease Models, Animal; Histamine; Hyperthermia, Induced; Hypothermia, Induced; Male; Mice, Inbred C57BL; Ovalbumin; Pruritus; Regional Blood Flow; Serotonin; Skin; TRPM Cation Channels; TRPV Cation Channels

Pruritus is the major symptom of ocular allergy but currently available treatments are often ineffective. Previous studies demonstrated that subpopulations of primary sensory neurons express Fc receptors and may contribute to antigen-specific pain. We investigated the role of neuronal Fc-epsilon Receptor I (FcεRI) in allergic ocular pruritus. Ovalbumin (OVA) was used as allergen together with alum adjuvant (OVA+alum) to produce a mouse model of ocular allergy with a significant elevation in the serum levels of both antigen-specific IgE and IgG. Mice sensitized by OVA without alum only induced elevation of serum IgG but not IgE. Scratching behavior toward the eyes with the hindlimb was used as an indicator of ocular itch. Topical OVA challenging to the eye dose-dependently induced scratching toward the eye in the OVA+alum sensitized mice, but not those sensitized by OVA only. The antigen-induced scratching was largely abolished by topical application of the blocking antibody to FcεRIα, but was only partially alleviated by pretreatment of mast cell stabilizer or histamine I receptor antagonist. The expression of FcεRI was detected in subpopulations of trigeminal ganglion (TG) neurons including those expressing pruriceptive markers and innervating the conjunctiva in the naïve mice. Moreover, FcεRI was found significantly upregulated in small-sized TG neurons in the OVA+alum sensitized mice. In acutely dissociated TG neurons, IgE-immune complex (IC), but not the antibody or antigen alone, induced intracellular calcium increase. The neuronal responses to IgE-IC could be specifically blocked by pre-application of a siRNA for FcεRIα. Our results indicate that FcεRI expressed on peripheral nociceptive neurons in the TG may be directly activated by IgE-IC and contribute to allergic ocular pruritus. This study may suggest a novel mechanism for the development of pathological itch in allergic diseases.

Topics: Alum Compounds; Animals; Disease Models, Animal; Eye Diseases; Hypersensitivity; Male; Mice; Mice, Inbred BALB C; Neurons; Ovalbumin; Pruritus; Receptors, IgE

The aim of the current study was to investigate the involvement of tryptase and protease-activated receptor-2 (PAR2) in the pathogenesis of itch using a recently developed murine model of atopic dermatitis (AD) elicited by epicutaneous sensitization with ovalbumin (OVA). We also examined whether tacrolimus exerts an antipruritic effect. Epicutaneous sensitization of BALB/c mice with OVA led to a significant increase in the number of scratches. Notably, PAR2 mRNA and protein levels as well as cutaneous levels of tryptase were significantly enhanced in epicutaneously sensitized mice. Pretreatment with the protease inhibitor, leupeptin, PAR2 antibody, and tacrolimus significantly reduced the number of degranulated mast cells and tryptase content, and consequently alleviated scratching behavior. Cetirizine (10mg/kg) exerted a significant inhibitory effect on the scratching behavior of mice, but did not affect the number of degranulated mast cells and induction of tryptase. Our results collectively suggest that tryptase and PAR2 are involved in OVA allergy-induced scratching behavior.

Topics: Allergens; Animals; Behavior, Animal; Dermatitis, Atopic; Disease Models, Animal; Female; Mice, Inbred BALB C; Ovalbumin; Pruritus; Receptor, PAR-2; RNA, Messenger; Skin; Tryptases

To normalize bacteriostasis and relieving itching external therapeutic function of Kochiae Fructus.. Itching guinea pig model caused by histamine, itching mice model, eczema guinea pig model caused by OVA, and inhibitory effect on pathogens in vitro were used to observe the itching threshold, symptoms and other related physiological index, as well as the inhibitory effect on the normal skin fungi by water extraction of Kochiae Fructus to evaluate the external therapeutic function of Kochiae Fructus.. The itching threshold of guinea pig itching model treated by water extraction of Kochiae Fructus at high, medium and low three dosage level, could be significantly increased when compared with negative control group (P < 0.05 or P < 0.01); Red speckle of OVA guinea pig model treated by water extraction of Kochiae Fructus at high, medium and low three dosage level, could be significantly decreased when compared with negative control group (P < 0.05 or P < 0.01); The number of itching and total time of itching within 30 minutes of mice model caused by R-glycose anhydride treated by water extraction of Kochiae Fructus at high, medium and low three dosage level, could be significantly decreased when compared with negative control group (P < 0.05 or P < 0.01); Several common skin fungi could be significantly inhibited by the water extraction of Kochiae Fructus. MIC of the water extraction of Kochiae Fructus on Trichophyton mentagrophytes, Trichophyton rubrum, Microsporum canis, Trichophyton violaceum, and Trichophyton schoenleini were 3.12%, 0.78%, 0.78%, 0.78%, 0.78%, respectively.. Kochiae fructus has the effect of bacteriostasis and relieving itching.

Topics: Administration, Cutaneous; Animals; Anti-Bacterial Agents; Antipruritics; Arthrodermataceae; Bassia scoparia; Disease Models, Animal; Drugs, Chinese Herbal; Eczema; Female; Fruit; Guinea Pigs; Histamine; Male; Mice; Microbial Sensitivity Tests; Microsporum; Ovalbumin; Pruritus; Skin; Trichophyton

To elucidate the possible involvement of nitric oxide (NO) derived from inducible NO synthase (iNOS) in the pathogenesis of patients with allergic rhinitis, we used an animal model of atopic dermatitis (AD) induced by epicutaneous sensitization and analysed the differences in ear thickness, the frequency of scratching and plasma levels of ovalbumin-specific immunoglobulin E (OVA-IgE), transforming growth factor (TGF)-β, tumor necrosis factor (TNF)-α, adrenocorticotropic hormone (ACTH) and α-melanocyte-stimulating hormone (α-MSH) between control and iNOS(-/-) mice. Eight-week-old control and iNOS(-/-) male C57BL/6j mice were sensitized three times with OVA antigen. Before and after the last skin sensitization, the number of scratching incidents and the thickness of the ear were examined, and the plasma levels of OVA-IgE, α-MSH, ACTH, TGF-β and TNF-α were analysed by ELISA. Sensitization of mice with OVA resulted in increased plasma levels of OVA-IgE, α-MSH, ACTH, TGF-β and TNF-α in control, but not in iNOS(-/-) mice. The administration of l-nitro-arginine-methyl ester (l-NAME) abolished all the above changes that occurred in the control mice. In addition, iNOS(-/-) mice given α-MSH exhibited a change similar to that seen in the control, whereas iNOS(-/-) mice given ACTH, TGF-β or TNF-α did not demonstrate any changes. These results indicate that symptoms of AD such as scratching can be exacerbated by α-MSH, which is induced by iNOS-derived NO.

Topics: Adrenocorticotropic Hormone; alpha-MSH; Animals; Dermatitis, Atopic; Disease Models, Animal; Enzyme Inhibitors; Histamine; Immunoglobulin E; Male; Mast Cells; Mice; Mice, Inbred C57BL; Mice, Knockout; NG-Nitroarginine Methyl Ester; Nitric Oxide Synthase Type II; Ovalbumin; Pruritus; Skin; Transforming Growth Factor beta; Tryptases; Tumor Necrosis Factor-alpha

The effects of cyclosporine A eye drops on the early-phase reaction were investigated in a type-I allergic conjunctivitis model.. Mice were actively sensitized with ragweed (RW) absorbed on aluminium hydroxide gel and challenged with RW for 10 days (single challenge model) or 10-14 days (repetitive challenge model) after the first sensitization. For the evaluation of itching, ovalbumin was used as an antigen instead of RW. The effects of cyclosporine A eye drops on increased vascular permeability, mast cell degranulation, and itching were evaluated and compared with those of other anti-allergic eye drops.. In the single challenge model, cyclosporine A eye drops significantly inhibited the increase in vascular permeability and histological evaluations showed suppressed degranulation of mast cells. Disodium cromoglycate (DSCG) eye drops showed only a slight tendency to inhibit the increase in both pathophysiological parameters. Ketotifen or betamethasone eye drops significantly inhibited the increase in vascular permeability. The order of potency in the single challenge model was ketotifen > cyclosporine A > betamethasone. In the repetitive challenge model, cyclosporine A eye drops significantly inhibited the increase in vascular permeability and DSCG eye drops showed only slight inhibition. Ketotifen or betamethasone significantly inhibited the increase in vascular permeability. The order of potency in the repetitive challenge model was cyclosporine A > betamethasone > ketotifen. The effect of cyclosporine A eye drops on the itch-scratch response was studied. Cyclosporine A and DSCG significantly reduced the itch-scratch response in the single and repetitive challenge models; the effect of cyclosporine A in the repetitive challenge model was more potent than in the single challenge model.. Those results suggest that administration of cyclosporine A eye drops inhibit the early-phase reaction in type-I allergic conjunctivitis, which may be mediated by the suppression of mast cell degranulation. This action of cyclosporine A eye drops may be involved in the therapeutic effect of cyclosporine A on allergic conjunctivitis.

Topics: Administration, Topical; Ambrosia; Animals; Anti-Allergic Agents; Betamethasone; Capillary Permeability; Cell Degranulation; Conjunctivitis, Allergic; Cromolyn Sodium; Cyclosporine; Disease Models, Animal; Immunosuppressive Agents; Ketotifen; Male; Mast Cells; Mice; Mice, Inbred BALB C; Ophthalmic Solutions; Ovalbumin; Pruritus

The present study was performed to study the participation of histamine H(3) receptors in nasal symptoms using Sch 50971, a potent and selective agonist of the H(3) receptor. Repeated topical application of antigen caused an increase in sneezing and nasal rubbing in sensitized mice. Oral administration of Sch 50971 and imetit, specific H(3)-receptor agonists, resulted in an inhibition of nasal symptoms induced by an antigen similar to an H(1)-receptor antagonist, cetirizine. Furthermore, simultaneous use of H(3)-receptor agonists, Sch 50971 or imetit, and an H(1)-receptor antagonist, cetirizine, caused a significant inhibitory effect on nasal symptoms at doses that showed no effect when used separately. The number of eosinophils in the nasal mucosa of mice sensitized with antigen was significantly decreased by cetirizine; however, Sch 50971 and imetit had no effect on eosinophil infiltration. These results clearly indicate that H(3) receptors are involved in the etiology of nasal allergy, and the stimulation of H(3) receptors may be useful as a novel therapeutic approach in nasal allergy.

Topics: Animals; Anti-Allergic Agents; Cetirizine; Chemotaxis, Leukocyte; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Synergism; Eosinophils; Female; Histamine Agonists; Histamine H1 Antagonists, Non-Sedating; Imidazoles; Mice; Mice, Inbred BALB C; Nasal Mucosa; Ovalbumin; Pruritus; Pyrrolidines; Receptors, Histamine H3; Rhinitis, Allergic, Perennial; Sneezing; Thiourea; Time Factors

The root of Paeonia lactiflora PALL (PL, Family Paeoniaceae) has been used frequently as an antipyretic and anti-inflammatory agent in traditional medicines of Korea, China and Japan. To evaluate antiallergic effect of PL, we isolated its main constituents, paeoniflorin and paeonol, and evaluated in vivo their inhibitory effects against passive cutaenous anaphylaxis (PCA) reaction induced by IgE-antigen complex and scratching behaviors induced by compound 48/80. PL, paeoniflorin and paeonol potently inhibited PCA reaction and scratching behaviors in mice. Paeoniflorin exhibited the most potent inhibition against scratching behaviors and the acetic acid-induced writhing syndrome in mice. Paeonol most potently inhibited PCA reaction and mast cells degranulation. These findings suggest that PL can improve IgE-induced anaphylaxis and scratching behaviors, and may be due to the effect of its constituents, paeoniflorin and paeonol.

Topics: Acetic Acid; Acetophenones; Analgesics; Animals; Anti-Allergic Agents; Antipruritics; Asthma; Behavior, Animal; Benzoates; Bridged-Ring Compounds; Cell Degranulation; Disease Models, Animal; Dose-Response Relationship, Drug; Glucosides; Male; Mast Cells; Mice; Mice, Inbred BALB C; Mice, Inbred ICR; Monoterpenes; Ovalbumin; p-Methoxy-N-methylphenethylamine; Paeonia; Pain; Pain Measurement; Passive Cutaneous Anaphylaxis; Plant Roots; Pruritus; Rats; Rats, Sprague-Dawley

The present study was performed to develop a new atopic dermatitis model characterized by not only itching but also inflammatory skin using BALB/c mice. From 18 days after the first systemic immunization, daily epicutaneous application of ovalbumin was performed for 2 weeks. Antigen challenge (ovalbumin) resulted in a significant increase of scratching behavior from day 23 to day 32. Moreover, skin symptoms such as erythema/hemorrhage, edema, excoriation/erosion and dryness/desquamation were also observed from day 19 to day 32. The frequency of scratching in the first stage (from day 24 to day 26 after the systemic first immunization) was decreased by chlorpheniramine and epinastine; however, in the last stage (from day 27 to day 30 after the systemic first immunization), both drugs showed no inhibition of scratching behavior. Therefore, an endogenous mediator other than histamine may be responsible for provoking the itching sensation in the last stage. Naloxone dose-dependently reduced the frequency of scratching in the last stage. Moreover, repeated local application of dexametasone significantly inhibited both scratching behavior and skin symptoms from day 24 to day 30. From these findings, it may be concluded that this model is essentially similar to atopic dermatitis in humans and could be used to elucidate the pathogenic mechanisms of atopic dermatitis and to develop appropriate new drugs for therapy.

Topics: Animals; Dermatitis, Atopic; Dexamethasone; Disease Models, Animal; Female; Histamine H1 Antagonists; Immunoglobulin E; Mice; Mice, Inbred BALB C; Naloxone; Ovalbumin; Pruritus; Skin

Artemisia princeps Pampanini (AP) was fermented with Bifidobacterium infantis K-525 and its antiasthmic effect investigated. AP and fermented AP (FAP) reduced the IgE level in the blood of ovalbumin-induced asthmic mice. Moreover, FAP reduced the IgE, proinflammatory cytokine IL-6, and IL-4 levels in the trachea, as well as in the lung of the experimental asthmic mice, whereas AP only reduced the IgE and IL-6 levels in the lungs. Nonetheless, AP and FAP both inhibited the mRNA expression of IL-6 and TNF-alpha in IgE-induced RBL-2H3 cells. The in vivo antiasthmic effect of FAP was more potent than that of AP. Therefore, these findings suggest that the enhanced antiasthmic effect of AP after bifidus fermentation was possibly due to the regulation of the proinflammatory cytokine biosynthesis of IL-6 and TNF-alpha.

Topics: Animals; Anti-Allergic Agents; Artemisia; Asthma; Bifidobacterium; Fermentation; Hypersensitivity; Immunoglobulin E; Interleukin-4; Interleukin-6; Lung; Mice; Mice, Inbred BALB C; Models, Animal; Ovalbumin; Plant Extracts; Pruritus; RNA, Messenger

In the present study, we investigated the participation of chemical mediators in the development of experimental allergic conjunctivitis in rats. Cetirizine (a histamine H1 receptor antagonist), ramatroban (a thromboxane A2 (TXA2) receptor antagonist) and zafirlukast (a cysteinyl leukotrienes (cys-LTs) receptor antagonist) were orally administered from day 14 to day 42 during repeated topical antigen challenge. An increase in reactivity to antigen- and histamine-induced eye scratching behavior was observed by topical sensitization in sensitized rats. Although increased reactivity to antigen was not influenced by cetirizine, ramatoroban and zafirlukast, increased reactivity to histamine was significantly inhibited by ramatroban. The development of conjunctival edema was also observed for topical sensitization. Cetirizine caused no inhibition of the development of conjunctival edema, but ramatroban and zafirlukast inhibited the development of conjunctival edema. In addition, the number of eosinophils in the conjunctiva was increased by topical sensitization. Cetirizine had no significant effect on the increase in the number of eosinophils. However, ramatroban and zafirlukast were effective in inhibiting an increase in the number of eosinophils induced by topical sensitization. These results indicate that TXA2 is involved in increased histamine reactivity, and TXA2 and cys-LTs are associated with not only the conjunctival edema but also eosinophil infiltration during the development of experimental allergic conjunctivitis in rats.

Topics: Administration, Oral; Animals; Carbazoles; Cetirizine; Conjunctivitis, Allergic; Disease Models, Animal; Edema; Eosinophilia; Histamine H2 Antagonists; Indoles; Leukotriene Antagonists; Male; Membrane Proteins; Ovalbumin; Phenylcarbamates; Pruritus; Rats; Rats, Wistar; Receptors, Histamine H2; Receptors, Leukotriene; Receptors, Thromboxane A2, Prostaglandin H2; Sulfonamides; Tosyl Compounds

We investigated the effects of 1-4% ointments of metronidazole and tinidazole (derivatives of nitroimidazole) on models of inflammatory dermatitis evoked by antigen, hapten and monoclonal anti-dinitrophenol (DNP) IgE antibody in mice. Metronidazole and tinidazole ointments (1) suppressed the late-phase reaction (LPR) of biphasic ear edema in mice sensitized with ovalbumin (OA), (2) suppressed trinitrochlorobenzene-induced inflammatory dermatitis, (3) suppressed the immediate phase reactions and LPR in mice passively sensitized with anti-DNP IgE mAb, and (4) enhanced vascular permeability and the number of scratching reactions, presumably due to itching, in passively sensitized mice. These results strongly indicate that metronidazole and tinidazole 1-4% ointments possess antiinflammatory, immunosuppressive and anti-itching effects, and have the potential for clinical use in the treatment of human inflammatory skin diseases including atopic dermatitis in addition to rosacea and acne vulgaris.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Antigens; Antipruritics; Capillary Permeability; Dermatitis; Dermatologic Agents; Disease Models, Animal; Edema; Humans; Immunosuppressive Agents; Male; Metronidazole; Mice; Ointments; Ovalbumin; Picryl Chloride; Pruritus; Tacrolimus; Tinidazole

The characteristics of the antihistamine effect of the new antiallergic compound TAK-427 were investigated.. In vitro binding assay of [(3)H] pyrilamine was performed using recombinant human histamine H(1) receptors (rhH(1)R). In vivo studies were performed in male ICR mice or Hartley guinea pigs. Drugs were administered orally 1 h before examinations. Determinations were made of histamine-induced skin reaction, ex vivo measured radioligand binding to brain and lung H(1) receptors, pentobarbital-induced sleeping time, passive cutaneous anaphylaxis (PCA) reaction, and antigen-induced itch-scratch responses (ISRs).. TAK-427 inhibited ligand binding to rhH(1)R with an IC(50) value of 17.3 nmol/l. TAK-427 inhibited histamine-induced skin reactions in guinea pigs and mice with an ID(50) value of 0.884 and 0.450 mg/kg, p.o., respectively; significant inhibition associated with 10 mg/kg of TAK-427 was still observed 24 h after dosing in guinea pigs. TAK-427 showed as high selectivity for peripheral H(1) receptors as terfenadine and epinastine did, which was evaluated by ex vivo measured radioligand binding. Even at 300 mg/kg, TAK-427 did not affect pentobarbital-induced sleeping time in mice. TAK-427 significantly inhibited PCA in mice and guinea pigs, and also inhibited antigen-induced ISRs in guinea pigs.. These results suggest that TAK-427 may have a long-lasting antihistamine activity with minimum sedative side effect and suppress acute phase allergic reactions.

Topics: Algorithms; Animals; Behavior, Animal; Binding, Competitive; Brain; Guinea Pigs; Histamine Antagonists; Histamine H1 Antagonists; Humans; Hypnotics and Sedatives; Imidazoles; Male; Mice; Mice, Inbred ICR; Ovalbumin; Passive Cutaneous Anaphylaxis; Pentobarbital; Pruritus; Pyridazines; Radioligand Assay; Receptors, Histamine H1; Recombinant Proteins; Sleep; Time Factors

The effects of nonsteroidal anti-inflammatory drugs (NSAIDs) on experimental allergic conjunctivitis, induced by ocular challenge with antigen in actively sensitized guinea pigs, were investigated. NSAIDs reduced the increase in prostaglandin D2 (PGD2) and E2 (PGE2) in the ocular lavage fluid. The inhibition of NSAIDs to these increases was approximately 90%-95%. NSAIDs also lowered itch-scratch response (ISR) to approximately one-third to one-half of the vehicle-treated group. However, these drugs scarcely affected plasma exudation in the conjunctiva. Ketotifen, an H1 histamine receptor antagonist, inhibited both pathophysiological changes (inhibition: 70%-80%). However, this drug was less efficacious than NSAIDs in reducing PGD2 and PGE2 levels. Moreover, topical administration of histamine induced ISR and plasma exudation; in contrast, PGD2 induced ISR exclusively. These results suggest that a part of antigen-induced ISR may be attributable to PGs. However, PGs may not play a key role in plasma exudation; other mediators such as histamine may be involved.

Topics: Administration, Topical; Animals; Anti-Inflammatory Agents, Non-Steroidal; Antigens; Benzophenones; Benzopyrans; Bromobenzenes; Conjunctivitis, Allergic; Diclofenac; Dinoprostone; Disease Models, Animal; Evans Blue; Exudates and Transudates; Eye; Guinea Pigs; Histamine; Histamine Release; Immunization; Injections, Intraperitoneal; Injections, Subcutaneous; Ketotifen; Male; Ovalbumin; Propionates; Prostaglandin D2; Pruritus; Therapeutic Irrigation

Topics: Animals; Arthrodermataceae; Biopsy; Dogs; Epidermophyton; Erythema; Female; Humans; Injections, Intradermal; Male; Ovalbumin; Peptide Hydrolases; Plant Extracts; Pruritus; Skin; Tinea; Trichophyton; Tyrosine