DOI: 10.1002/ame2.12503
Intratracheal instillation for the testing of pulmonary toxicity in mice—Effects of instillation devices and feed type on inflammation
Niels Hadrup1
Michael Guldbrandsen2
Eva Terrida2
Katja M.S.Bendtsen2
Karin S.Hougaard3
Nicklas R.Jacobsen2
Ulla Vogel4
1.National Research Centre for the Working Environment,Copenhagen,Denmark;Research Group for Risk-Benefit,National Food Institute,Technical University of Denmark,Copenhagen,Denmark2.National Research Centre for the Working Environment,Copenhagen,Denmark3.National Research Centre for the Working Environment,Copenhagen,Denmark;Department of Public Health,University of Copenhagen,Copenhagen,Denmark4.National Research Centre for the Working Environment,Copenhagen,Denmark;National Food Institute,Technical University of Denmark,Copenhagen,Denmark
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 250 μ L 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.
机标关键词：devicesfeedmiceeffectsinflammationinstillationintratrachealpulmonary
论文发表日期：2025-02-28
在线出版日期：2025-08-15（本平台首次上网日期，不代表文献的发表时间）
页数：9( 378-386 )
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