Alleviation of wood smoke-induced lung injury by tachykinin receptor antagonist and hydroxyl radical scavenger in guinea pigs

You Shuei Lin, Ching Yin Ho, Gau Jun Tang, Yu Ru Kou

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

We recently reported that wood smoke inhalation initially (within 5 min) causes airway injury and subsequently produces both airway and parenchymal injury after a delay (within 2 h). In this study, we investigated the mediator mechanisms of this delayed smoke-induced lung injury in 126 anesthetized and artificially ventilated guinea pigs who received challenges of either air or 40 tidal breaths of wood smoke. Two hours after inhalation, wood smoke produced various injurious responses, including increases in alveolar-capillary permeability, microvascular permeabilities, and histological injury scores, in airway and parenchymal tissues. Pre-treatment given before smoke challenge with CP-96,345 [a tachykinin NK1 receptor antagonist; (2S,3S)-cis-2-(diphenylmethyl)-N-((2-methoxyphenyl)-methyl)-1-aza bicyclo(2.2.2.)-octan-3-amine], dimethylthiourea (a hydroxyl radical scavenger), or a combination of these two drugs largely alleviated both the airway and parenchymal responses, whereas pre-treatment with SR-48,968 [a tachykinin NK2 receptor antagonist; (S)-N-methyl-N(4-(4-acetylamino-4-phenylpiperidino)-2-(3,4-dichlorophenyl)- butyl)benzamide] or a combination of CP-96,344 and SR-48,965 (inactive enantiomers) failed to do so. Post-treatment given at 5 min after smoke challenge with CP-96,345 or dimethylthiourea significantly alleviated the parenchymal responses, while having no effect on the airway responses. Pre-treatment with dimethylthiourea prevented the smoke-induced reduction in airway neutral endopeptidase activity (an enzyme for tachykinin degradation). We concluded that (1) tachykinins and hydroxyl radical play important roles in producing smoke-induced delayed lung injury in guinea pigs, and both may be involved in the spread of injury from the airways to the pulmonary parenchyma, and (2) the contribution of tachykinins is mediated via the activation of tachykinin NK1 receptors, and is associated with the hydroxyl radical-induced inactivation of airway neutral endopeptidase.

Original languageEnglish
Pages (from-to)141-148
Number of pages8
JournalEuropean Journal of Pharmacology
Volume425
Issue number2
DOIs
Publication statusPublished - Aug 10 2001
Externally publishedYes

Fingerprint

Tachykinin Receptors
Lung Injury
Smoke
Hydroxyl Radical
Guinea Pigs
Tachykinins
Neprilysin
Wounds and Injuries
Capillary Permeability
Inhalation
Drug Combinations
Amines
Air
Lung

Keywords

  • Hydroxyl radical
  • Neutral endopeptidase
  • Pulmonary edema
  • Tachykinin
  • Toxic smoke

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Pharmacology

Cite this

Alleviation of wood smoke-induced lung injury by tachykinin receptor antagonist and hydroxyl radical scavenger in guinea pigs. / Lin, You Shuei; Ho, Ching Yin; Tang, Gau Jun; Kou, Yu Ru.

In: European Journal of Pharmacology, Vol. 425, No. 2, 10.08.2001, p. 141-148.

Research output: Contribution to journalArticle

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