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.
Department of Toxicology, Faculty of Pharmacy, Medical University, Lodz, Poland.
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Galoch
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Sapota
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Skrzypinska-Gawrysiak
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Kilanowicz
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