AGE-DEPENDENT DIFFERENTIAL-EFFECTS OF CIGARETTE-SMOKE ON HEPATIC AND PULMONARY XENOBIOTIC-METABOLIZING ENZYMES IN RATS

The effects of cigarette smoke (CS) on hepatic and pulmonary monooxyge nase (MO) activities (aniline 4-hydroxylase, AH; aminopyrine N-demethy lase, AMND, 7-ethoxyresorufin O-deethylase, EROD; p-nitroanisole O-dem ethylase, p-NAOD), lipid peroxidation (LP), and reduced glutathione (G SH) levels and glutathione S-transferase (GST) activities toward sever al substrates (1-chloro-2,4-dinitrobenzene, CDNB; 1,2-dichloro-4-nitro benzene, DCNB; ethacrynic acid, EAA; 1,2-epoxy-3-(p-nitrophenoxy)-prop ane, ENPP) were determined in 20-, 90- and 360-day-old male rats. The animals were exposed to CS five times a day, with 1 h intervals, for 3 days in a chamber supplied alternatively with smoke and fresh air, an d were killed 16 h after the last treatments. The hepatic AH activity increased significantly in 20-day-old rats and remained unaltered in o lder age groups. The hepatic AMND activity unaltered, significantly in creased and decreased in 20-, 90 and 360-day-old rats? respectively. T he pulmonary AH activity increased significantly in 20- and 90-day-old rats whereas no alteration was noted in 360-day-old rats. CS was inef fective on pulmonary AMND activity at all ages. CS increased hepatic a nd pulmonary EROD and p-NAOD activities significantly in all age group s compared to controls. In liver, LP level was significantly increased , decreased, and unaltered in 20-, 90- and 360-day-old rats, respectiv ely. CS increased hepatic GSH level significantly in 90-day-old rats b ut was not effective in the other age groups. In lung, LP level was in creased in 90- and 360-day-old rats and unaltered in 20-day-old rats. CS increased pulmonary GSH level significantly in 90-day-old mts and d id not have any effect in the other age groups. The hepatic GST activi ties toward CDNB and DCNB decreased significantly in 360-day-old rats and were unaltered in the younger age groups. The hepatic GST activity toward EAA was unaltered, significantly increased and decreased in 20 -, 90- and 360-day-old rats! respectively. The hepatic GST activity to ward ENPP decreased significantly in 20- and 90-day-old rats but was u naltered in the oldest group of rats. In 20-day-old rats, the pulmonar y GST activity toward ENPP increased significantly whereas the other G ST activities did not alter. In 90-day-old rats, however, CS significa ntly decreased all the pulmonary CST activities studied. Unaltered DCN B GST, significant increase in EAA GST and decrease in CDNB and ENPP G ST activities of lung were noted in 360-day-old rats. These results re veal that the regulation in rats of hepatic and pulmonary MO and GST a ctivities are differentially influenced by CS as a function of age.