El-Merhibi A, Kumar A, Smeaton T
School of Pharmaceutical, Molecular and Biomedical Sciences, University of South Australia, Adelaide, SA 5000, Australia.
Ecotoxicol Environ Saf. 2004 Feb;57(2):202-12. doi: 10.1016/S0147-6513(03)00082-4.
The use of chemical inhibitors/inducers is one of the strategies employed to determine whether a particular metabolic pathway is involved in the metabolism of a xenobiotic. The objective of this study was to assess the role of piperonyl butoxide (PBO) on the toxicity of an organophosphorus insecticide, chlorpyrifos (CPF) to two species, Ceriodaphnia dubia (waterflea) and Xenopus laevis (South African clawed frog). Chlorpyrifos was highly toxic to C. dubia (48-h LC50: 0.05 microg/L) in comparison with X. laevis (96-h LC50: 2410 microg/L). Piperonyl butoxide at 200 microg/L reduced the toxicity of chlorpyrifos to C. dubia by a factor of 6. Piperonyl butoxide at 3000 microg/L also reduced the toxicity of CPF to X. laevis with respect to mortality and malformations. Acetylcholinesterase (AChE) activity was used as a biomarker to further assess the role of PBO in chlorpyrifos toxicity. X. laevis exposed to CPF and PBO exhibited a biphasic response in terms of AChE activity with an initial increase in the AChE activity followed by a drastic decrease. The results from the present study indicate that C. dubia and X. laevis have the capability to metabolize chlorpyrifos via cytochromes P450 mediated reactions. The results also indicate that the use of the biomarker AChE is useful in determining metabolic processes of organophosphorus insecticides, which require metabolic activation.
使用化学抑制剂/诱导剂是用于确定特定代谢途径是否参与异生物代谢的策略之一。本研究的目的是评估胡椒基丁醚(PBO)对有机磷杀虫剂毒死蜱(CPF)对两种生物——大型蚤(水蚤)和非洲爪蟾(南非爪蟾)毒性的影响。与非洲爪蟾(96小时半数致死浓度:2410微克/升)相比,毒死蜱对大型蚤毒性极高(48小时半数致死浓度:0.05微克/升)。200微克/升的胡椒基丁醚使毒死蜱对大型蚤的毒性降低了6倍。3000微克/升的胡椒基丁醚在死亡率和畸形方面也降低了毒死蜱对非洲爪蟾的毒性。乙酰胆碱酯酶(AChE)活性被用作生物标志物,以进一步评估PBO在毒死蜱毒性中的作用。暴露于CPF和PBO的非洲爪蟾在AChE活性方面表现出双相反应,即AChE活性先增加,随后急剧下降。本研究结果表明,大型蚤和非洲爪蟾有能力通过细胞色素P450介导的反应代谢毒死蜱。结果还表明,使用生物标志物AChE有助于确定需要代谢活化的有机磷杀虫剂的代谢过程。