Neutral endopeptidase (NEP) and its role in pathological pulmonary change with inhalation exposure to JP-8 jet fuel.
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.
Pfaff
J K
JK
Department of Pediatrics, University of Arizona Health Sciences Center, Tucson 85724, USA.
Tollinger
B J
BJ
Lantz
R C
RC
Chen
H
H
Hays
A M
AM
Witten
M L
ML
D000280:Administration, Inhalation; D000401:Aircraft; D000818:Animals; D001980:Bronchi / Q000187:drug effects / Q000473:pathology; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D004848:Epithelium / Q000473:pathology; D006838:Hydrocarbons / Q000633:toxicity*; D008171:Lung Diseases / Q000139:chemically induced* / Q000201:enzymology* / Q000473:pathology; D008297:Male; D015260:Neprilysin / Q000502:physiology*; D010578:Petroleum / Q000633:toxicity*; D051381:Rats; D011916:Rats, Inbred F344; D013373:Substance P / Q000378:metabolism / Q000502:physiology; D015320:Tachykinins / Q000502:physiology; D013997:Time Factors
D006838:Hydrocarbons; D010578:Petroleum; D015320:Tachykinins; D013373:Substance P; D015260:Neprilysin