Routine use of tobacco products may modify physiological and metabolic functions, including drug metabolizing enzymes, which may impact the pharmacokinetics of environmental contaminants. Chlorpyrifos is an organophosphorus (OP) insecticide that is bioactivated to chlorpyrifos-oxon, and manifests its neurotoxicity by inhibiting acetylcholinesterase (AChE). The objective of this study was to evaluate the impact of repeated nicotine exposure on the pharmacokinetics of chlorpyrifos (CPF) and its major metabolite, 3,5,6-trichloro-2-pyridinol (TCPy) in blood and urine and also to determine the impact on cholinesterase (ChE) activity in plasma and brain. Animals were exposed to 7-daily doses of either 1mg nicotine/kg or saline, and to either a single oral dose of 35mg CPF/kg or a repeated dose of 5mg CPF/kg/day for 7 days. Groups of rats were then sacrificed at multiple time-points after receiving the last dose of CPF. Repeated nicotine and CPF exposures resulted in enhanced metabolism of CPF to TCPy, as evidenced by increases in the measured TCPy peak concentration and AUC in blood. However, there was no significant difference in the amount of TCPy (free or total) excreted in the urine within the first 24-h post last dose. The extent of brain acetylcholinesterase (AChE) inhibition was reduced due to nicotine co-exposure consistent with an increase in CYP450-mediated dearylation (detoxification) versus desulfuration. It was of interest to note that the impact of nicotine co-exposure was experimentally observed only after repeated CPF doses. A physiologically based pharmacokinetic model for CPF was used to simulate the effect of increasing the dearylation V(max) based upon previously conducted in vitro metabolism studies. Predicted CPF-oxon concentrations in blood and brain were lower following the expected V(max) increase in nicotine treated groups. These model results were consistent with the experimental data. The current study demonstrated that repeated nicotine exposure could alter CPF metabolism in vivo, resulting in altered brain AChE inhibition.
A somatic embryogenesis and plant regeneration study was conducted with a rare and endangered species, Acanthopanax seoulenses, and various factors affecting somatic embryo induction were evaluated. The frequency of embryogenic callus induction was slightly better on wounded seeds compared with non-wounded ones. The optimum medium to induce somatic embryos (SEs) from embryogenic cells was MS medium supplemented with 3% sucrose and 0.1À0.2 mg/l abscisic acid (ABA), or MS medium with 3% sucrose and 0.1 mg/l ABAþ0.02% activated charcoal. Gibberellic acid resulted in a positive effect on SE germination, but there were no differences in the range of 0.1 to 1.0 mg/l. SE germination and plant conversion rate were different in the two gelling agents: agar-gelled medium was slightly better than gelite-gelled medium, and the highest plant conversion, 78AE18.2%, was achieved in agar-gelled medium. Regenerated plantlets were successfully acclimatized in artificial soil mixture, and more than 98% of the plants survived in vermiculite or an equal volume mixture of vermiculite and peat moss. Results suggest that the rare and endangered species is able to propagate effectively via the somatic embryogenesis system.
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