Alterations in tissue glutathione and angiotensin converting enzyme due to inhalation of diesel engine exhaust.

Abstract

Quantitative changes in reduced glutathione (GSH) and angiotensin converting enzyme (ACE) of lung and extrapulmonary tissues were determined following exposure of laboratory animals to diesel engine exhaust (DEE). Exposure of male rats and guinea pigs to DEE containing 750 micrograms particulates per cubic meter for 12 wk did not cause any changes in GSH levels of lung, liver, and heart compared to control values. Rats were then exposed for various time periods to 6 mg/m3 DEE. Two weeks of exposure produced statistically significant increases of 21 and 7% in GSH levels of lung and liver, respectively, but not change in the heart. Following 4 wk of exposure, lung showed a 14% increase and heart an 11% increase in GSH level. Furthermore, rats exposed for 4 wk to DEE did not show any particular susceptibility toward the GSH-depleting effect of acetaminophen as compared to controls. A significant depletion (15%) of hepatic GSH was observed after 8 wk of exposure, while lung was still showing an increase of 18% in GSH and heart was unaffected. Time-dependent increases of 18 and 33% in serum ACE activity were noted after 4 and 8 wk of exposure. Pulmonary ACE activity did not decrease until after 8 wk, and then to a small extent (7%). The observed increases in GSH may have been related to the presence of NO2 in the DEE. On the other hand, the depletion of hepatic GSH suggests production of electrophilic compounds due to an induction of metabolic activity of liver. The change in serum ACE activity may be due to time-requiring perturbations in the pulmonary endothelial cells.