Toxicological Sciences, Vol 49, 225-231, Copyright © 1999 by Society of Toxicology
JJ Stanek and JB Morris
At exposure concentrations of 750 ppm or more, acetaldehyde is a rodent
inhalation carcinogen that induces nasal tumors. Aldehyde dehydrogenase
(ALDH) is thought to be an important detoxifying enzyme for aldehydes.
Although nasal tissues express ALDH, the importance of this enzyme relative
to delivered dosage rates at high-inspired concentrations is not well
defined. To provide such information, uptake of inspired acetaldehyde was
measured at an inspiratory flow rate that approximated the minute
ventilation rate in the surgically isolated nasal cavity of F 344 rats
pretreated with either saline (control) or the ALDH inhibitor, cyanamide
(10 mg/kg s.c.). ALDH activities (substrate concentration 3 times the K(m))
in anterior (respiratory mucosa) and posterior (olfactory mucosa) nasal
tissues averaged 160 and 210 nmol/min), respectively, in control animals
(total activity 370 nmol/min), compared to 60 and 80 nmol/min,
respectively, in cyanamide- pretreated rats (p < 0.05), indicating that
approximately 60% inhibition was obtained. Nasal uptake was measured at 3
inspired concentrations: 10, 300, and 1500 ppm. At these concentrations,
acetaldehyde uptake efficiency averaged 54, 37, and 34% in saline-
pretreated rats, respectively (p < 0.05). In absolute terms, the
delivered dosage rates at these exposure concentrations averaged 21, 420,
and 1990 nmol/min. The concentration dependence on uptake suggests a
saturable process was involved. At inspired concentrations of 300 ppm or
more, the delivered dosage rates exceeded the measured specific activity
for nasal ALDH of 370 nmol/min. Cyanamide pretreatment abolished the
concentration dependence. Specifically, uptake efficiencies in
cyanamide-pretreated rats averaged 30, 27, and 31% at inspired
concentrations of 10, 300, and 1500 ppm, respectively (p > 0.05);
delivered dosage rates were 12, 310, and 1780 nmol/min. Thus, cyanamide
pretreatment reduced nasal-delivered dosage rates at inspired
concentrations of 10, 300, and 1500 ppm, respectively by 9, 110, and 210
nmol/min, values that correspond well with the total nasal ALDH activity of
370 nmol/min. In toto, these results suggest that inspired acetaldehyde is
metabolized in situ by ALDH, but at exposure concentrations of 300 ppm or
greater, the delivered dosage rate may equal or exceed the capacity of this
enzyme.
ARTICLES
The effect of inhibition of aldehyde dehydrogenase on nasal uptake of inspired acetaldehyde
University of Connecticut, Storrs 06269-2092, USA.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  M. Yoon, M. C. Madden, and H. A. Barton Developmental Expression of Aldehyde Dehydrogenase in Rat: a Comparison of Liver and Lung Development Toxicol. Sci., February 1, 2006; 89(2): 386 - 398. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. B. Morris, M. I. Banton, and L. H. Pottenger Uptake of Inspired Propylene Oxide in the Upper Respiratory Tract of the F344 Rat Toxicol. Sci., September 1, 2004; 81(1): 216 - 224. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. B. Morris, P. T. Symanowicz, J. E. Olsen, R. S. Thrall, M. M. Cloutier, and A. K. Hubbard Immediate sensory nerve-mediated respiratory responses to irritants in healthy and allergic airway-diseased mice J Appl Physiol, April 1, 2003; 94(4): 1563 - 1571. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. B. Morris Uptake of Styrene in the Upper Respiratory Tract of the CD Mouse and Sprague-Dawley Rat Toxicol. Sci., March 1, 2000; 54(1): 222 - 228. [Abstract] [Full Text] [PDF]
|
|