Induction of nasal carboxylesterase in F344 rats following inhalation exposure to pyridine.
Carboxylesterases (CEs) in the nasal mucosa metabolize some inhaled esters, including industrially important acrylates and acetates, to toxic acid metabolites that produce site-specific lesions in the nasal epithelium. The metabolic capacity of CEs in the normal nasal mucosa is theoretically sufficient to protect the lower respiratory tract from toxicant-induced injury at concentrations of acrylates and acetates likely to be inhaled in industrial environments. Thus, alterations in the metabolism and toxicity of these substrates would be predicted with changes in the amount or activity of CE in the nasal mucosa. Although many other nasal enzymes have been reported to be relatively refractory to induction, the amount of CE in the nasal mucosa can be increased by inhalant exposure. In the liver, expression of CEs may be elevated in response to exposure to P450 inducers. To examine this phenomenon in the nose with the widely used industrial solvent pyridine, we examined the effect of pyridine inhalation at the threshold limit value concentration of 5 ppm, or at 444 ppm, 6 hr/day for 4 days on the localization and amount of immunoreactive CE in olfactory mucosas of F344/N rats. CE immunoreactivity was increased in Bowman's glands following exposure to 5 or 444 ppm pyridine, and in sustentacular cells most notably following the 5 ppm exposure. Quantitative densitometry showed a statistically significant, dose-related increase in the density of immunoreactive CE in Bowman's glands of pyridine-exposed rats. These results indicate pyridine, and possibly other solvents, can induce nasal CE, an enzyme not directly involved in the metabolism of those solvents, following low-dose, short-term exposure.(ABSTRACT TRUNCATED AT 250 WORDS)
Nikula
K J
KJ
Inhalation Toxicology Research Institute, Wayne State University, Albuquerque, NM 87185, USA.
Novak
R F
RF
Chang
I Y
IY
Dahl
A R
AR
Kracko
D A
DA
Zangar
R C
RC
Kim
S G
SG
Lewis
J L
JL
D000280:Administration, Inhalation; D000818:Animals; D043182:Carboxylesterase; D002265:Carboxylic Ester Hydrolases / Q000096:biosynthesis* / Q000276:immunology; D004305:Dose-Response Relationship, Drug; D004790:Enzyme Induction; D007150:Immunohistochemistry; D008297:Male; D009831:Olfactory Mucosa / Q000187:drug effects* / Q000201:enzymology*; D011725:Pyridines / Q000633:toxicity*; D051381:Rats; D011916:Rats, Inbred F344; D012680:Sensitivity and Specificity
D011725:Pyridines; D002265:Carboxylic Ester Hydrolases; D043182:Carboxylesterase; C023666:pyridine