ABSTRACT
AIMS: The present study was performed to evaluate the effect of mometasone furoate on a nasal congestion model in Brown Norway rats. METHODS: Nasal congestion in rats sensitized with toluene-2,4-diisocyanate (TDI) was measured using whole-body plethysmography which allowed animals to move freely. RESULTS: Penh (enhanced pause), an index of nasal congestion, was significantly increased after 5% TDI challenge in sensitized rats compared with that in non-sensitized rats. The peak of the increase in Penh appeared at 1 and 5 h after TDI challenge. A single topical administration of mometasone furoate (0.05%) at 1 h before TDI challenge suppressed the increase of Penh in sensitized rats. A significant effect was observed 5-6 h after nasal administration. Almost the same results were obtained with fluticasone propionate (0.05%). CONCLUSION: Mometasone furoate may therefore be effective and have a rapid onset of action in nasal congestion when used clinically as with fluticasone propionate.
Subject(s)
Anti-Allergic Agents/pharmacology , Nasal Obstruction/drug therapy , Pregnadienediols/pharmacology , Administration, Topical , Androstadienes/pharmacology , Animals , Disease Models, Animal , Fluticasone , Male , Mometasone Furoate , Nasal Mucosa/drug effects , Nasal Mucosa/physiopathology , Plethysmography, Whole Body , Rats , Rats, Inbred BN , Respiratory Mechanics/drug effects , Time FactorsABSTRACT
The effects of hop extracts (Humulus lupulus L.) on histamine release from rat peritoneal mast cells and human basophilic KU812 cells were studied. Hop water extract (HWE) and XAD-4 50% methanol fraction of HWE (MFH) inhibited histamine release from rat mast cells induced by compound 48/80 at concentrations of 100 and 10 mug/ml, respectively. Almost the same findings were observed with A23187-induced histamine release from KU812 cells. Next, we studied the effects of hop extracts on antigen-induced nasal rubbing and sneezing in sensitized BALB/c mice. HWE caused a significant inhibition of nasal rubbing and sneezing at a dose of 500 mg/kg. MFH also inhibited nasal rubbing and sneezing dose-dependently. A significant difference was observed from 100 mg/kg in nasal rubbing and 200 mg/kg in sneezing. The effects of both extracts became clear after repeated administration. HWE and MFH significantly inhibited both nasal rubbing and sneezing, respectively, after consecutive treatment for 15 d at smaller doses compared with single administration. This finding indicates that the active component of hop is included in MFH, which was absorbed to Amberlite XAD-4 and eluted with 50% methanol. These results clearly demonstrated that hop extracts may be effective in the relief of symptoms of allergic rhinitis.
Subject(s)
Anti-Allergic Agents , Humulus/chemistry , Rhinitis, Allergic, Seasonal/drug therapy , Sneezing/drug effects , Animals , Basophils/drug effects , Basophils/metabolism , Behavior, Animal/drug effects , Cell Line , Dose-Response Relationship, Drug , Female , Histamine Release/drug effects , Mast Cells/drug effects , Mast Cells/metabolism , Mice , Mice, Inbred BALB C , Plant Extracts/pharmacology , Rats , Rhinitis, Allergic, Seasonal/psychologyABSTRACT
The aim of this study was to develop and characterize a new model for evaluating nasal congestion in rats by using whole body plethysmography (WBP)-free moving application. Brown Norway rats were sensitized with 10% toluene-2, 4-diisocyanate (TDI) solution, and nasal congestion was provoked with 5% TDI. An increase in the enhanced pause (Penh) was recognized after being challenged with TDI. In addition, a significant increase in the Penh was observed following the intranasal application of histamine in TDI sensitized rats. Histamine H1 antagonists, such as chlorpheniramine and ketotifen suppressed the increase of Penh during the early-phase response. On the other hand, epinastine suppressed the increase of Penh in both the early and late phase responses. In conclusion, we developed an allergic rhinitis model that includes nasal congestion symptoms in Brown Norway rats, and this model may be useful for evaluating the effects of drugs on nasal congestion.
Subject(s)
Histamine H1 Antagonists/pharmacology , Nasal Mucosa/drug effects , Rhinitis/chemically induced , Toluene 2,4-Diisocyanate/pharmacology , Animals , Chlorpheniramine/pharmacology , Dibenzazepines/pharmacology , Disease Models, Animal , Histamine/pharmacology , Imidazoles/pharmacology , Ketotifen/pharmacology , Male , Nasal Mucosa/physiopathology , Plethysmography, Whole Body , Rats , Rats, Inbred BNABSTRACT
The effect of ethanol extract obtained from Bulgaria inquinans on the scratching behavior and vascular permeability changes induced by compound 48/80, histamine and serotonin in ICR mice was studied. The extract dose-dependently inhibited scratching behavior induced by compound 48/80 and serotonin. A significant inhibition was observed at doses of 300 and 600 mg/kg when Bulgaria inquinans extract was administered orally. However, no inhibitory effect was observed on the histamine-induced scratching behavior by the extract, even at a dose of 600 mg/kg. In addition, it also inhibited the increase in the vascular permeability induced by compound 48/80 and serotonin at doses of 300 and 600 mg/kg; however, it failed to inhibit the increased vascular permeability induced by histamine, even at a dose of 600 mg/kg. Bulgaria inquinans extract showed a potent inhibitory effect on histamine release induced by compound 48/80. These results suggest that Bulgaria inquinans extract is effective in cutaneous pruritus and erythema, which were probably mediated by inhibiting the release of histamine from mast cells and antagonizing the effect on serotonin.
Subject(s)
Ascomycota/chemistry , Complex Mixtures/pharmacology , Erythema/prevention & control , Pruritus/prevention & control , Administration, Oral , Animals , Ascomycota/isolation & purification , Behavior, Animal/drug effects , Capillary Permeability/drug effects , Complex Mixtures/administration & dosage , Complex Mixtures/chemistry , Cyproheptadine/pharmacology , Dose-Response Relationship, Drug , Drug Evaluation, Preclinical , Erythema/chemically induced , Erythema/drug therapy , Female , Histamine/adverse effects , Histamine/metabolism , Ketotifen/pharmacology , Male , Mast Cells/drug effects , Mast Cells/metabolism , Mice , Mice, Inbred ICR , Pruritus/chemically induced , Pruritus/drug therapy , Rats , Rats, Wistar , Serotonin , Suspensions/administration & dosage , p-Methoxy-N-methylphenethylamineABSTRACT
The present study was undertaken to clarify the effects of mometasone on nasal symptoms induced by repeated intranasal application of antigen in sensitized rats in comparison with that of chlorpheniramine. Rats received mometasone intranasally or chlorpheniramine orally 1 h before a topical antigen challenge for 7 days. Mometasone caused a decrease in the instances of nasal rubbing and an inhibition of this response was observed during the treatment period. Almost identical findings were observed with chlorpheniramine. This response was inhibited, even after the interruption of mometasone treatment, while such an effect was not observed with chlorpheniramine. On day 36, the changes in sensitivity to histamine were investigated. Unlike chlorpheniramine, hypersensitivity to histamine was significantly reduced in the mometasone-treated group. The passive cutaneous anaphylaxis titers were elevated and reached a maximum 8 days after the start of the topical antigen challenge. The passive cutaneous anaphylaxis titer in the mometasone-treated group was significantly lower than that in the control group. The results indicated that mometasone is effective in allergic rhinitis, not only during the period of application, but also after the interruption of application.
Subject(s)
Anti-Allergic Agents/therapeutic use , Rhinitis, Allergic, Seasonal/prevention & control , Administration, Intranasal , Animals , Anti-Allergic Agents/administration & dosage , Antigens/administration & dosage , Antigens/immunology , Behavior, Animal/drug effects , Chlorpheniramine/administration & dosage , Chlorpheniramine/therapeutic use , Disease Models, Animal , Histamine/administration & dosage , Histamine/immunology , Male , Mometasone Furoate , Pregnadienediols/administration & dosage , Pregnadienediols/therapeutic use , Rats , Rats, Wistar , Rhinitis, Allergic, Seasonal/immunology , Time FactorsABSTRACT
To confirm the effectiveness of loratadine for relieving pruritus in atopic dermatitis, we examined the effect of this drug using animal models of atopic dermatitis associated pruritus in ICR and hairless mice. As for the results, in ICR mice, single oral administration of loratadine at a dose of 5 or 10 mg/kg significantly inhibited the dorsal scratching behavior induced by histamine or an antigen, and the effect of loratadine was more potent than that of fexofenadine and chlorpheniramine. In hairless mice, oral administration of loratadine at a dose of 10 mg/kg for 6 days significantly inhibited the facial scratching behavior induced by the feeding of a low magnesium diet. Furthermore, oral administration of loratadine at a dose of 10 mg/kg for 7 days also significantly inhibited the histamine-induced scratching behavior in the same animals. These results indicate that loratadine may be effective in preventing pruritus associated with atopic dermatitis.
Subject(s)
Dermatitis, Atopic/drug therapy , Histamine H1 Antagonists, Non-Sedating/therapeutic use , Loratadine/therapeutic use , Animals , Female , Histamine/pharmacology , Mice , Mice, Hairless , Mice, Inbred ICRABSTRACT
We studied the effect of Lo Han Kuo (Siraitia grosvenori Swingle) on histamine-induced nasal rubbing and compound 48/80-induced skin scratching behavior in ICR mice. An extract and glycoside (a complex of sweet components) of Lo Han Kuo were used in the study. Both the extract and glycoside caused no significant effect on nasal rubbing or scratching behavior, even at a dose of 1000 mg/kg when administered in a single dose. However, the effect of Lo Han Kuo became clear after repeated administration, and 300 and 1000 mg/kg of both extract and glycoside significantly inhibited nasal rubbing and skin scratching behavior after consecutive treatment for 4 weeks. Both the extract and glycoside inhibited the histamine release induced by compound 48/80 at concentrations of 300 and 1000 microg/ml. From these results, it is assumed that the inhibition of nasal rubbing and skin scratching behavior induced by Lo Han Kuo occurs through a mast cell-dependent mechanism.
