Quantifiable morphologic evaluation of paraquat pulmonary toxicity in rats

The intent of this study was to detect paraquat (PQ)-induced, dose-dependent variations, in rat lungs, by analyzing several quantifiable morphologic parameters. Male Wistar rats (6-week old) received single doses (0, 7, 10, 25 or 40 mg/kg body weight) of PQ dichloride by sc injection. The parameters examined were number of alveolar type II cells, number of intra-alveolar free cells, total number of cells constituting the pulmonary interstitium, and alveolar wall thickness. Our maximum dose produced a marked decrease, 3 days post-injection, in the number of alveolar type II cells in contrast to the observed increases in all other dosage groups. These increases in other groups were inversely proportional to the increasing PQ dosages. All rats that received the maximum dose died within 4 days after injection and therefore could not be compared to the control group for our parameters after 6 days. After 9 days, the number of type II cells had decreased significantly in the 25 mg/kg group. The two highest dosage groups, on the third day, had significantly more intra-alveolar free cells. The total number of cells constituting the pulmonary interstitium in all groups increased in proportion to the increasing dosages from 3 to 9 days post-injection. In the 10 and 25 mg/kg groups, alveolar wall thickness was notably increased from days 6 to 9. PQ dosing produced dose-dependent variations in all of the parameters examined. This model of PQ-induced pulmonary toxicity may be useful in evaluating prophylactic or therapeutic agents.