EFFECTS OF MOTORCYCLE EXHAUST INHALATION EXPOSURE ON CYTOCHROME P-450 2B1, ANTIOXIDANT ENZYMES, AND LIPID PEROXIDATION IN RAT LIVER AND LUNG

Abstract

The effects of motorcycle exhaust (ME) on metabolic and antioxidant enzymes and lipid peroxidation were determined using male rats exposed to 1:10 diluted ME by inhalation 2h daily for 4wk. For microsomal cytochrome P-450 enzymes, ME resulted in threefold increases of 7ethoxyresorufin and pentoxyresorufin O-deethylase activities in liver and a sixfold increase of 7-ethoxyresorufin O-deethylase activity and an 80% decrease of pentoxyresorufin O-dealkylase activity in lung. The results of immunoblot analysis of microsomal proteins revealed that ME increased liver and lung cytochrome P-450 1A1 with minimal effects on cytochrome P-450 2E1. ME increased cytochrome P-450 2B1/2 proteins in liver but decreased cytochrome P-450 2B1 in lung. ME did not change microsomal cytochrome P-450 enzyme activity or protein level in kidney. For phase II enzymes, ME resulted in 53% and twofold increases of cytosolic NAD(P)H:quinone oxidoreductase activities in liver and lung, respectively, and no effect on microsomal UDP-glucuronosyltransferase activities. For antioxidant enzymes, ME produced 23% and 35% decreases of superoxide dismutase, 9% and 27% decreases of catalase, and no changes of glutathione peroxidase activities in liver and lung cytosols, respectively. For lipid peroxidation, the results of thiobarbituric acid assay showed that ME resulted in a twofold increase of formation of malondialdehyde by liver microsomes incubated with FeCl₃-ADP. ME produced a threefold increase of malondialdehyde formation by lung microsomes. The present study demonstrates that ME inhalation exposure differentially modulates cytochrome P-450 2B1 and antioxidant enzymes and increases susceptibility to lipid peroxidation in rat liver and lung.

The authors thank Dr. Sang S. Park and Dr. F. Peter Guengerich for the antibodies to cytochrome P-450s and Chen-Yi Chen for technical assistance. This work was supported by grants NSC-91-2320-B002-124 from the National Science Council, Republic of China, and DOH91-0543-003B from National Health Research Institutes, Department of Health, Republic of China.