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 hepatic and pulmonary monooxygenase (MO) activities (aniline 4-hydroxylase (AH), aminopyrine N-demethylase (AMND), 7-ethoxyresorufin O-deethylase (EROD), p-nitroanisole O-demethylase (p-NAOD)), lipid peroxidation (LP) and reduced glutathione (GSH) levels and glutathione S-transferase (GST) activities toward several substrates (l-chloro-2,4-dinitrobenzene (CDNB), 1,2-dichloro-4-nitrobenzene (DCNB), ethacrynic acid (EAA), 1,2-epoxy-3-(p-nitrophenoxy)-propane (ENPP)) were determined and compared 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 significantly whereas GST activity for EAA decreased significantly in liver 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 activity toward DCNB, significantly. No alterations were noted in pulmonary MO activities and GST activity toward EAA and GSH level by EtOH treatment. When the animals were exposed to CS five times a day, with 1 h intervals, for 3 days in a chamber where smoke and fresh air lead alternatively, 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 activities toward CDNB and DCNB. In lung, CS increased AH, EROD and p-NAOD activities and LP and GSH levels and decreased all the GST activities studied 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, augmentation of elevations were noted in AH and p-NAOD activities and LP and GSH levels but not in EROD and AMND activities in liver. Combined treatment significantly decreased GST activity toward CDNB, ameliorated the alteration caused by either EtOH or CS treatment alone on GST activity toward EAA and potentiated the depression of GST activity toward ENPP to a greater degree. No change was observed in GST activity toward DCNB. In lung, combined treatment potentiated the elevations of AMND and p-NAOD activities and LP level and not those of AH and EROD activities. GST activities toward CDNB, DCNB and ENPP were highly elevated by the combined treatment. No changes were observed in pulmonary GSH level and GST activity for EAA by the combined treatment. These results reveal that the regulations of the hepatic and pulmonary MO and GST are differentially influenced by EtOH, CS and the combined treatment.
Eke
B C
BC
Department of Toxicology, Faculty of Pharmacy, Ankara University, Turkey.
Vural
N
N
Işcan
M
M
D000633:Aminopyrine N-Demethylase / Q000378:metabolism; D000815:Aniline Hydroxylase / Q000378:metabolism; D000818:Animals; D019363:Cytochrome P-450 CYP1A1 / Q000378:metabolism; D000431:Ethanol / Q000633:toxicity*; D005978:Glutathione / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D015227:Lipid Peroxidation; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008168:Lung / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D010088:Oxidoreductases / Q000378:metabolism*; D010090:Oxidoreductases, O-Demethylating / Q000378:metabolism; D010947:Plants, Toxic; D051381:Rats; D012906:Smoke / Q000009:adverse effects*; D014026:Nicotiana; D015262:Xenobiotics / Q000378:metabolism*
D012906:Smoke; D015262:Xenobiotics; D000431:Ethanol; C026048:4-nitroanisole O-demethylase; D010088:Oxidoreductases; D010090:Oxidoreductases, O-Demethylating; D000815:Aniline Hydroxylase; D019363:Cytochrome P-450 CYP1A1; D000633:Aminopyrine N-Demethylase; D005982:Glutathione Transferase; D005978:Glutathione