Kinetics of respiratory tract absorption and plasma clearance of horseradish peroxidase in guinea pigs.

Horseradish peroxidase (HRP) absorption across the wall of the upper airway, monitored by the amount detected in the blood, is used to measure epithelial damage by toxins. Full details of kinetics of absorption and blood clearance have not been reported previously. We measured the kinetics under the experimental conditions used in testing toxins. HRP was administered to guinea pigs either by intraarterial injection of a 7.5 microgram bolus (plasma clearance) or by intratracheal instillation of 1 mg (respiratory tract absorption). Plasma concentrations were monitored for 60 min. Plasma concentrations of HRP rose linearly with time after intratracheal instillation, reaching 236 +/- 51 ng/ml (mean +/- SE) at 60 min after instillation. HRP was cleared from the plasma rapidly after bolus injection. The elimination coefficient, k2, determined from the biphasic log normal plot, was 0.322 min-1. These data were used to estimate the kinetics of absorption across the respiratory epithelium. A single 3-hr exposure to an atmosphere containing 2.5 mg/m3 of submicrometer zinc oxide particles increased plasma concentration of HRP after intratracheal deposition (407 +/- 63 ng/ml at 60 min) and had no effect on plasma clearance (k2 = 0.342 min-1). Therefore plasma concentrations of HRP measured after intratracheal deposition can be used as a sensitive indicator to evaluate the effects of inhalation of a test atmosphere on epithelial permeability, if plasma clearance kinetics are not altered by the exposure.