Abstract
The intraperitoneal administration of 2-isopropylnaphthalene (2-IPN) (3000 mg/kg) to rats resulted in an increase of phospholipids and phosphatidylcholine in the pulmonary lavage fluid. The fatty acid composition of the phosphatidylcholine in the fluid of rats so treated, however, was unchanged from that of untreated animals. Prior treatment of rats with piperonyl butoxide, a known cytochrome P-450 inhibitor, resulted in an inhibition of the above increase of phospholipids and phosphatidylcholine. In contrast, prior treatment with diethyl maleate, which induced depletion of reduced glutathione (GSH) in the tissue, enhanced the effect of 2-IPN on phospholipid and phosphatidylcholine contents in the pulmonary lavage fluid. To confirm the possible participation of GSH, pulmonary nonprotein-SH (NP-SH) was determined. Treatment with 2-IPN resulted in a decrease of NP-SH, and the administration of 2-IPN to rats pretreated with diethyl maleate caused a significant decrease of NP-SH compared to 2-IPN given without pretreatment. From these results, it is suggested that reactive metabolites such as 2-IPN-epoxides are produced, leading to an increase in secretion of pulmonary surfactant from alveolar Type II cells.
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