Acute toxicity of polychlorinated naphthalenes and their effect on cytochrome P450

Abstract

Polychlorinated naphthalenes (PCNs) are able to induce cytochrome P-450-dependent microsomal monooxygenase 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.