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The Effect of Arsenic Trioxide on Airway Inflammation in Asthmatic Rats Following Ovalbumin Challenge

Author: DingLiRen
Tutor: ShenHuaHao
School: Zhejiang University
Course: Internal Medicine ( Respiratory Disease )
Keywords: asthmatic model eosinophils arsenic trioxide interleukin-5 interferon-gamma
CLC: R562.25
Type: Master's thesis
Year: 2001
Downloads: 49
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Abstract


BackgroundAsthma is a chronic inflammatory disease characterized by eosinophilic airway inflammation, variable airflow obstruction and hyperresponsiveness (AHR). Many effecter cells and cytokines play an important role in the development of asthma, of which eosinophils and interleukin-5 (IL-5) are the most important. Recently more and more emphases are placed on anti-inflammation of airway, so administration of corticosteroids (CS) becomes the most effective treatment. However the prevalence and mortality rate of asthma is inclined to increase, not decrease. Until now there is much problem in the managements of asthma and CS cannot solve all question in asthma. So many doctors are devoted to looking for some new and effective drugs and therapy. In China asthma has been treated by our traditional medicine for more than one thousand years, of which the arsenic trioxide had been used widely. Although its antiasthmatic effect was recognized very earlier, it has been overlooked for a long time because it has some side effect and invention ofinhaled CS in 1960s. Now there is limited treatment for asthma except for CS, so the action of arsenic trioxide has been recognized again. Even so there is few data about this area and hardly no information about its effect on Eos and IL-5, which are the most important cells and mediator respectively. We first observed its effect on Eos in a rat of asthmatic model and investigated its possible mechanism compared with BUD, a sort of CS, which is very convincingly effective for asthma. Material and methodsAnimals: Male Sprague Dawley rats weighting about 130g were distributed into the following groups: sensitized group (Group or OVA group), arsenic trioxide treat groups (AT groups, 3 dose) budesonide treat group (BUD group), normal control group (NC group).Research design: S group, AT group, and BUD group were sensitized with ovalbumin (OVA) mixed with aluminum hydroxide in saline, NC group were treated with the same agent except for OVA. A week after sensitization AT groups were administrated by arsenic trioxide solution (i.p.) according to the corresponding dose continually for seven days. Ten days after sensitization BUD group was exposed to aerosolized BUD (2.5mg/kg per day) for 4 days. Two weeks after sensitization S group, AT groups and BUD group were exposed to aerosolized OVA while NC group exposed to saline. Twenty-four hours after OVA challenge all rats of every group were killed to collect blood, BALF and bone marrow cells suspension, cell counts and differentials after Wright-Giemsa stain were made. Keep serum and the supernatant of BALF after centrifugation at -20 癈, ready for detecting the level of IL-5 and IFN- y. Statistics Methods: All results are expressed as the mean 盨d. Differencebetween groups for BM WBC and eosinophils, and IL-5, IFN-y content were determined by analysis of variance (ANOVA). BALF WBC and eosinophils were evaluated with the Mann-Whitney rank sum test. Statistical significance was claimed when p<0.05. Results1. Results of BALF: After challenge WBC and Eos of S group, AT group land group 2 were significantly higher than other groups. There is no difference among these groups, but the number of WBC and Eos of AT group 3 (dose of 2.0mg/kg per day) is lower than S group (p <0.05), but higher than that of NC group. Compared with NC group, WBC and Eos in BALF have change little and there is no difference (p >0.05). Based on these we can deduce that AT can inhibit to some extent, not completely the airway inflammation.2. Results of bone marrow: There is no difference in WBC and Eos among all groups in total. But Eos of S group is higher than NC, and the Eos of AT group 3 (dose of 2.omg/kg/d) is lower than that of S group. So we can deduce that AT may have an effect on the production of Eos, though there is no difference among all groups.3. Results of content of cytokines: After challenge IL-5 level in serum and BALF of S group is higher than other groups, but the results of IFN-y are to the contrary. Following th

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CLC: > Medicine, health > Internal Medicine > Respiratory system and chest diseases > Trachea and bronchial disease > Bronchial disease > Bronchial asthma
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