Intratracheal instillation for the testing of pulmonary toxicity in mice-Effects of instillation devices and feed type on inflammation  

作　　者：Niels Hadrup Michael Guldbrandsen Eva Terrida Katja M.S.Bendtsen Karin S.Hougaard Nicklas R.Jacobsen Ulla Vogel 

机构地区：[1]National Research Centre for the Working Environment,Copenhagen,Denmark [2]Research Group for Risk-Benefit,National Food Institute,Technical University of Denmark,Copenhagen,Denmark [3]Department of Public Health,University of Copenhagen,Copenhagen,Denmark [4]National Food Institute,Technical University of Denmark,Copenhagen,Denmark

出　　处：《Animal Models and Experimental Medicine》2025年第2期378-386,共9页动物模型与实验医学(英文)

基　　金：This work was supported by the Focused Research Effort on Chemicals in the Working Environment(FFIKA)from the Danish Government.

摘　　要：Background:Inhalation exposure is the gold standard when assessing pulmonary tox-icity.However,it typically requires substantial amounts of test material.Intratracheal instillation is an alternative administration technique,where the test substance is suspended in a liquid vehicle and deposited into the lung via the trachea.Instillation requires minimal test material,delivers an exact dose deep into the lung,and is less labor-intensive than inhalation exposures.However,one shortcoming is that the pro-cedure may induce short-term inflammation.To minimize this,we tested different modifications of the technique to identify the potential for refinement.Methods:First,we tested whether previous findings of increased inflammation could be confirmed.Next,we tested whether instillation with a disposable 1 mL syringe with ball-tipped steel-needle(Disposable-syringe/steel-needle)induced less inflammation than the use of our standard set-up,a 250μL reusable glass syringe with a disposable plastic catheter(Glass-syringe/plastic-catheter).Finally,we tested if access to pelleted and liquid feed prior to instillation affected inflammation.We evaluated inflammation by neutrophil numbers in bronchoalveolar fluid 24 h post-exposure.Results:Vehicle-instilled mice showed a small increase in neutrophil numbers com-pared to untreated mice.Neutrophil numbers were slightly elevated in the groups in-stilled with Disposable-syringe/steel-needle;an interaction with feed type indicated that the increase in neutrophils was more pronounced in combination with feed pel-lets compared to liquid feed.We found no difference between the feed types when using the Glass-syringe/plastic-catheter combination.Conclusion:The Glass-syringe/plastic-catheter combination induced the least exposure-related inflammation,confirming this as a preferred instillation procedure.

关 键 词：INHALATION MOUSE PULMONARY TOXICITY 

分 类 号：TG1[金属学及工艺—金属学]