Acute toxicity of polychlorinated naphthalenes and their effect on cytochrome P450.
Polychlorinated naphthalenes (PCNs) are able to induce cytochrome P-450-dependent microsomal mono-oxygenase activities in vivo and in vitro. The aim of this study was to investigate the toxicity of a PCN mixture, and its effect on the levels of cytochrome P-450 in rats. The animals were intragastrically administered a mixture of PCNs in single doses of 250, 500 and 1000 mg/kg b.w. Dissection of animals was performed 24, 72 and 240 hours after administration. After PCN administration (all doses) the body weight loss (up to 30% in comparison with the control group, 240 hours after administration) and an increase of relative liver mass (about 126-153% of controls, 72 hours after administration) were observed. The exposure to PCN evoked an increase in the level of total cytochrome P-450 as well as the activity of CYP 1A (mediated 7-ethoxyresorufin O-deethylation) at all time points. The maximum activity of CYP 1A (about 12- to 15-fold increase in comparison with the control group) was observed 72 hours after dosing. Malondialdehyde (MDA), determined in the liver, showed a high increase and 240 hours after administration, the level of MDA was about one order of magnitude greater in comparison with control.
Galoch
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Department of Toxicology, Faculty of Pharmacy, Medical University, Lodz, Poland.
Sapota
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Skrzypinska-Gawrysiak
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M
Kilanowicz
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D000208:Acute Disease; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D056486:Chemical and Drug Induced Liver Injury / Q000201:enzymology* / Q000209:etiology; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006843:Hydrocarbons, Chlorinated / Q000633:toxicity*; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects* / Q000201:enzymology; D009281:Naphthalenes / Q000633:toxicity*; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar
D006843:Hydrocarbons, Chlorinated; D009281:Naphthalenes; D003577:Cytochrome P-450 Enzyme System