Pulmonary ultrastructure after oral and intravenous dosage of paraquat to rats.

Paraquat was administered to rats by gavage or intravenously at doses which were approximately equitoxic (680 mu. moles/kh and 65 mu. moles/kg respectively) and the lungs examined by light and electron microscopy at intervals up to 48 hours. No significant changes were observed in alveolar endothelial cells at any of the time intervals studied. After intravenous administration the first ultrastructural changes were observed at 4 hr in the type I cells which were less electron dense and contained few organelles. At 8 hr these lesions were more marked and in some places the basement memebrane was denuded. Type II cells were also showing damage to mitochondria and loss of microvilli. After oral dosing, the type and sequence of changes was similar but the first changes were not seen until 22 hr. Intravenous injection of 0-03 micron carbon particles 1 hr before killing showed no significant leakage from the alveolar endothelium. This study provides no morphological evidence that the oedema of the lung caused by paraquat in rats is due to damage to endothelial cells. It appears that, following dosing by the two routes, the difference in interval between dosing and the development of lesions is due to the accumulation of paraquat. Lesions in type I cells therefore occurred when a certain concentration of paraquat is known to be present in the lung. It is suggested that a prime compartment into which paraquat is accumulated is the alveolar epithelial cell.