The effect of inhibition of aldehyde dehydrogenase on nasal uptake of inspired acetaldehyde

At exposure concentrations of 750 ppm or more, acetaldehyde is a rodent inh alation carcinogen that induces nasal tumors. Aldehyde dehydrogenase (ALDH) is thought to be an important detoxifying enzyme for aldehydes. Although n asal tissues express ALDH, the importance of this enzyme relative to delive red dosage rates at high-inspired concentrations is not well defined. To pr ovide 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 salin e (control) or the ALDH inhibitor, cyanamide (10 mg/kg sc). ALDH activities (substrate concentration 3 times the K-m) in anterior (respiratory mucosa) and posterior (olfactory mucosa) nasal tissues averaged 160 and 210 nmol/m in, respectively, in control animals (total activity 370 nnol/min), compare d to 60 and 80 nmol/min, respectively, in cyanamide-pretreated rats (p < 0. 05), indicating that approximately 60% inhibition was obtained. Nasal uptak e was measured at 3 inspired concentrations: 10, 300, and 1500 ppm. At thes e concentrations, acetaldehyde uptake efficiency averaged 54, 37, and 34% i n saline-pretreated rats, respectively (p < 0.05). In absolute terms, the d elivered dosage rates at these exposure concentrations averaged 21, 420, an d 1990 nmol/min. The concentration dependence on uptake suggests a saturabl e process was involved. At inspired concentrations of 300 ppm or more, the delivered dosage rates exceeded the measured specific activity for nasal AL DH of 370 nmol/min. Cyanamide pretreatment abolished the concentration depe ndence. Specifically, uptake efficiencies in cyanamide-pretreated rats aver aged 30, 27, and 31% at inspired concentrations of 10, 300, and 1500 ppm, r espectively (p > 0.05); delivered dosage rates were 12, 310, and 1780 nmol/ min. Thus, cyanamide pretreatment reduced nasal-delivered dosage rates at i nspired concentrations of 10, 300, and 1500 ppm, respectively by 9, 110, an d 210 nmol/min, values that correspond well with the total nasal ALDH activ ity of 370 nmol/min. In tote, these results suggest that inspired acetaldeh yde is metabolized in situ by ALDH, but at exposure concentrations of 300 p pm or greater, the delivered dosage rate may equal or exceed the capacity o f this enzyme.