| Mizolastine is a new benzimidazol derivative, whose pharmacological activity is due to a selective blockade of H1-histamine receptors, to the inhibition of mastocyte histamine release, and to the recruitment of inflammatory cells (eosinophils and neutrophils). Moreover, It is reported that mizolastine via in-vitro animal models was shown to inhibit 5-lipoxygenase(5-LO) activity, and then to inhibit inflammatory effect by decreasing the release of leukotrienes(LT). Hypersensitivity diseases induced by IgE were found with complicated mechanisms. In addition to histamine, mast cells also release other inflammatory mediums, such as cytokines, chemokines, neuropeptide and enzymes, and so on. It may explain why patients intaking H1-antagonists have few therapeutic effect in clinical treatments. Recently, arachidonic acid metabolites (such as leukotrienes) and TH2 cytokines some in obstinate inflammation diseases aroused great interest. Our studies included two parts: (1) Mice were perfused with mizolastine and other control drugs, and after that were induced by Intradermal injection of SP, and then epithelial tissue were isolated and homogenate was made. Competitive Enzyme-linked immunosorbent assay (ELISA) was applied to detect the levels of LTB4 and IL-5 in homogenate supernates. The aim of part I test was to observe whether mizolastine can inhibit the release of leukotrieneB4 and interleukin 5 from epithelial tissue of mice induced by SP. (2) Mice were sensitized by intraperitoneal injections of OVA to achieve allergic model of animals. The spleen lymphocytes were isolated and incubated with mizolastine solution of different concentrations or other control solution prior to re-challenge with OVA. Competitive ELISA was applied to detect the levels of LTB4 and IL-5 in cell culture supernates. The aim of part II test was to observe whether mizolastine can inhibit the release of leukotriene B4 and interleukin 5 from spleen lymphocytes of mice sensitized by OVA.Part IInhibition of Leukotriene B4 and Interleukin 5 Release from skin of Mice by Mizolastine1. Materials and Methods1.1 Animal groups19-21g Balb/c mice with 5-7weeks provided by the center of Animal Experiment, College of Medical Sciences, Zhejiang University were randomly divided into two groups, and then each group was randomly divided into six groups againgroup I: NS Pretreatment+ Intradermal injection of NSgroup II: NS Pretreatment+Intradermal injection of SPgroup III: Mizolastine 3mg/kg Pretreatment+Intradermal injection of SPgroup IV: Mizolastine 10mg/kg Pretreatment+Intradermal injection of SPgroup V: Rolatadine 10mg/kg Pretreatment+Intradermal injection of SPgroup VI: Dexamethasone 3mg/kg Pretreatment+Intradermal injection of SP1.2 MethodsMice were pretreated with NS,mizolastine and other control drugs, and 1h later intradermally injected by SP in the skin over the back, and then the first group mice were killed and their skin were isolated and homogenate was made five minutes later.Competitive enzyme-linked immunosorbent assay (ELISA) was applied to detect the levels of LTB4 in homogenate supernates. For 24h later, the levels of IL-5 was detected in the same way. 1.3 Statistical analysesResults were presented as means SD (x s), and data were analyzed by SPSS 10.0 for windows. a=5% was considered as statistically significance2. Results2.1 Effect of mizolastine or other control drugs on the release of LTB4 in the skin of mice induced by SP(Table 1)The LTB4 level in group II were 5.53 1.88pg/ml, showing significant difference when compared to that in group I. It meant that SP can induce the release of leukotriene B4 in the skin of mice. The LTB4 level in group III or IV shown significant difference when compared to those in group II, suggesting that mizolastine remarkably inhibited the release of LTB4 at the dose of 3mg/kg and l0mg/kg. Moreover, higher dose of mizolastine showed greater effect. The LTB4 level in group IV showeds significant difference when compared... |
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