COMBINED EFFECTS OF ETHANOL AND CIGARETTE-SMOKE ON HEPATIC AND PULMONARY XENOBIOTIC-METABOLIZING ENZYMES IN RATS

The combined effects of ethanol (EtOH) and cigarette smoke (CS) on hep atic and pulmonary monooxygenase (MO) activities (aniline 4-hydroxylas e (AH), aminopyrine N-demethylase (AMND), 7-ethoxyresorufin O-deethyla se (EROD), p-nitroanisole O-demethylase (p-NAOD)), lipid peroxidation (LP) and reduced glutathione (GSH) levels and glutathione S-transferas e (GST) activities toward several substrates (1-chloro-2,4-dinitrobenz ene (CDNB), 1,2-dichloro-4-nitrobenzene (DCNB), ethacrynic acid (EAA), 1,2-epoxy-3-(p-nitrophenoxy)-propane (ENPP)) were determined and comp ared with those of EtOH or CS alone in rats. When the male adult rats (225-275 g) were treated with 10% EtOH (v/v) in their drinking for 21 days AH, AMND and EROD activities and LP and GSH levels increased sign ificantly whereas GST activity for EAA decreased significantly in live r as compared to controls. EtOH did not change the hepatic p-NAOD and GST activities toward CDNB, DCNB and ENPP. In lung, EtOH increased GST activities toward CDNB and ENPP and LP level but decreased GST activi ty toward DCNB, significantly. No alterations were noted in pulmonary MO activities and GST activity toward EAA and GSH level by EtOK treatm ent. When the animals were exposed to CS five times a day. with 1 h in tervals, for 3 days in a chamber where smoke and fresh air lead altern atively, AMND, EROD and p-NAOD activities, GST activity toward EAA and GSH level increased but LP level and GST activity for ENPP decreased significantly in liver. CS did not alter the hepatic AH and GST activi ties toward CDNB and DCNB. In lung, CS increased AH, EROD and p-NAOD a ctivities and LP and GSH levels and decreased all the GST activities s tudied significantly. CS had no influence on pulmonary AMND activity. For the combined treatment, the animals were treated with 10% EtOH (v/ v) in their drinking water for 21 days and during the last 3 days they were exposed to CS five times a day, with 1 h intervals, in a chamber where smoke and fresh air lead alternatively. In these animals, augme ntation of elevations were noted in AK and p-NAOD activities and LP an d GSH levels but not in EROD and AMND activities in liver. Combined tr eatment significantly decreased GST activity toward CDNB, ameliorated the alteration caused bq either EtOH or CS treatment alone on GST acti vity toward EAA and potentiated the depression of GST activity toward ENPP to a greater degree. No change was observed in GST activity towar d DCNB. In lung, combined treatment potentiated the elevations of AMND and p-NAOD activities and LP level and not those of AH and EROD activ ities. GST activities toward CDNB, DCNB and ENPP were highly elevated by the combined treatment. No changes were observed in pulmonary GSH l evel and GST activity for EAA by the combined treatment. These results reveal that the regulations of the hepatic and pulmonary MO and GST a re differentially influenced by EtOH, CS and the combined treatment. C opyright (C) 1996 Elsevier Science Ireland Ltd.