Neutral endopeptidase (NEP) and its role in pathological pulmonary change with inhalation exposure to JP-8 jet fuel

• Published in: Toxicology and industrial health Vol. 12; no. 1; p. 93
• Main Authors: Pfaff, J K, Tollinger, B J, Lantz, R C, Chen, H, Hays, A M, Witten, M L
• Format: Journal Article
• Language: English
• Published: England 01-01-1996
• Subjects: Administration, Inhalation; Aircraft; Animals; Bronchi - drug effects; Bronchi - pathology; Bronchoalveolar Lavage Fluid - chemistry; Epithelium - pathology; Hydrocarbons - toxicity; Lung Diseases - chemically induced; Lung Diseases - enzymology; Lung Diseases - pathology; Male; Neprilysin - physiology; Petroleum - toxicity; Rats; Rats, Inbred F344; Substance P - metabolism; Substance P - physiology; Tachykinins - physiology; Time Factors
• ISSN: 0748-2337
• DOI: 10.1177/074823379601200106

Through a simulated flightline exposure protocol, Fischer 344 rats (F344) were subjected to an aerosol/vapor mix of the military jet fuel, JP-8. Previous studies with this model of lung injury have revealed significant increases in pulmonary resistance, increased alveolar clearance of 99mTcDTPA, and a decrease in bronchoalveolar lavage fluid (BALF) concentration of the neuropeptide substance P (SP). Exposures to JP-8 were nose-only and for one hour daily. Six groups of Fischer 344 rats were exposed for 7, 28, or 56 days at two JP-8 concentrations (low dose = 469-520 mg/m3/hr, high dose = 814-1263 mg/m3/hr). Exposed groups were matched with longitudinal controls. In response to JP-8 inhalation, exposure animals demonstrated a dose-dependent as well as duration-determined reduction in BALF SP concentration. Both JP-8 concentrations caused significant pathological changes in lower pulmonary structures.