Low concentration of phenol in medical solutions can induce bronchoconstriction and toxicity in murine, rat and human lungs
| Autor: | Jan Spillner, Elisabeth Breuer, Annette D. Rieg, Julia Krabbe, Thomas Schröder, Sebastian Kalverkamp, Christian Martin, Svetlana Kintsler, Galina Balakirski, Till Braunschweig, Thomas Schettgen, Ingo Krüger |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
021110 strategic
defence & security studies Preservative Inhalation business.industry 0211 other engineering and technologies 02 engineering and technology Pharmacology 021001 nanoscience & nanotechnology chemistry.chemical_compound chemistry Toxicity Medicine Phenol Bronchoconstriction medicine.symptom 0210 nano-technology business Cytotoxicity IC50 Acetylcholine medicine.drug |
| Zdroj: | Airway pharmacology and treatment. |
| DOI: | 10.1183/13993003.congress-2018.pa1059 |
| Popis: | Background: Toxic effects of high doses of phenol have been demonstrated in different species, however low concentrations are considered to be harmless and are still used as preservatives in some medical products approved for inhalation. We investigated effects of low concentrations of phenol regarding bronchoconstriction and toxicity in murine, rat and human precision-cut lung slices (PCLS). Methods: PCLS were prepared from agarose-filled lungs of different species. Cytotoxicity was determined after 1 h and 24 h of phenol exposure by WST-1 and LDH assay. Bronchoconstriction was monitored by videomicroscopy. Concentration-response curves were performed in the presence and absence of phenol diluted in medium (1 µg/ml - 3.2 mg/ml). Acetylcholine 10 mM and potassium chloride 10 M were used to determine maximal bronchoconstriction. Results: After 24 h phenol exposure, toxicity was determined by WST-1 (mitochondrial activity) resulting in IC50 of 1.7 mg/ml in all species; significantly increased LDH release started at 1 mg/ml. After 1 h exposure with phenol, IC50 for WST-1 was observed at concentrations of 2.97, 4.69 and 3.42 mg/ml in mice, rat and human respectively. At 1 mg/ml phenol concentration, the airway area in PCLS reduced to 80% and 60% of the initial airway in rat and human PCLS, respectively. This represents a strong bronchoconstriction. Conclusions: In PCLS, phenol concentrations as low as 0.1% cause strong bronchoconstriction and beginning toxicity. Bronchoconstriction was more potent in human compared to rat lungs. As concentrations of 0.5% of phenol are found in medical solutions, these might lead to local toxicity and airway obstruction in humans. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|