Novel Aerosol Treatment of Airway Hyper-Reactivity and Inflammation in a Murine Model of Asthma with a Soluble Epoxide Hydrolase Inhibitor

Details

• Personal Author:
  Chen J ; Chen Z ; Hammock BD ; Li W ; Li X ; Mack S ; Pinkerton KE ; Takeuchi M ; Tan B ; Tsuji K ; Wagner K ; Wan D ; Wang C ; Wu C-W ; Yang J ; Zhang C ; Zhang J
• Description:
  Asthma currently affects more than 339 million people worldwide. In the present preliminary study, we examined the efficacy of a new, inhalable soluble epoxide hydrolase inhibitor (sEHI), 1-trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl) urea (TPPU), to attenuate airway inflammation, mucin secretion, and hyper-responsiveness (AHR) in an ovalbumin (OVA)-sensitized murine model. Male BALB/c mice were divided into phosphate-buffered saline (PBS), OVA, and OVA+TPPU (2- or 6-h) exposure groups. On days 0 and 14, the mice were administered PBS or sensitized to OVA in PBS. From days 26-38, seven challenge exposures were performed with 30 min inhalation of filtered air or OVA alone. In the OVA+TPPU groups, a 2- or 6-h TPPU inhalation preceded each 30-min OVA exposure. On day 39, pulmonary function tests (PFTs) were performed, and biological samples were collected. Lung tissues were used to semi-quantitatively evaluate the severity of inflammation and airway constriction and the volume of stored intracellular mucosubstances. Bronchoalveolar lavage (BAL) and blood samples were used to analyze regulatory lipid mediator profiles. Significantly (p < 0.05) attenuated alveolar, bronchiolar, and pleural inflammation; airway resistance and constriction; mucosubstance volume; and inflammatory lipid mediator levels were observed with OVA+TPPU relative to OVA alone. Cumulative findings indicated TPPU inhalation effectively inhibited inflammation, suppressed AHR, and prevented mucosubstance accumulation in the murine asthmatic model. Future studies should determine the pharmacokinetics (i.e., absorption, distribution, metabolism, and excretion) and pharmacodynamics (i.e., concentration/dose responses) of inhaled TPPU to explore its potential as an asthma-preventative or -rescue treatment. [Description provided by NIOSH]
• Subjects:
  Animals Asthma Asthma, Occupational Biopharmaceutics Drug Therapy Lung Occupational Health Respiratory System Respiratory Tract Diseases Safety
• Keywords:
  Airway Resistance Animal Studies Drug Therapy Lung Tissue Medicinal Chemicals Pharmaceuticals Pulmonary Function Respiratory Diseases
• ISSN:
  1932-6203
• Document Type:
  Text
• Funding:
  Cooperative Agreement
• Genre:
  Journal Article
• Place as Subject:
  California ; OSHA Region 9
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  17
• Issue:
  4
• NIOSHTIC Number:
  nn:20067925
• Citation:
  PLoS One 2022 Apr; 17(4):e0266608
• Contact Point Address:
  Kent E. Pinkerton, Center for Health and the Environment, University of California, Davis, California, United States of America
• Email:
  kepinkerton@ucdavis.edu
• Federal Fiscal Year:
  2022
• Performing Organization:
  University of California - Davis
• Peer Reviewed:
  True
• Start Date:
  20010930
• Source Full Name:
  PLoS One
• End Date:
  20270929
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:2b5d7570057faefcfadc11aabb5c56727f166c14d45de43356ef9f1d9c7c4346f209689b9871275bf7102417f70575952bb2c7741d15c9dcbb8fac5b9bdaf620
• Download URL:
  https://stacks.cdc.gov/view/cdc/230159/cdc_230159_DS1.pdf
• File Type:
  [PDF - 1.93 MB ]