Integrative assessment of enantioselectivity in endocrine disruption and immunotoxicity of synthetic pyrethroids
Introduction
Enantioselectivity of chiral contaminants in biological and environmental processes is considered in an increasing number of studies (Lewis et al., 1999, Liu et al., 2005a). In these studies, a wide range of toxicological endpoints have been evaluated, which include mortality (Liu et al., 2005a), bioaccumulation (Wiberg et al., 2000), biodegradation (Lewis et al., 1999), and lately chronic toxicities such as neurotoxicity (Zhou et al., 2007), endocrine disruption (Wang et al., 2007), and developmental toxicity (Xu et al., 2008a, Xu et al., 2008b). For instance, some chiral pesticides are known to have endocrine disruption potential as endocrine disruption chemicals (EDCs) (Zhao et al., 2008), and several studies demonstrated stark selectivity between enantiomers in their ability to induce estrogenic responses (Wang et al., 2007, 2009). Moreover, strong chiral selectivity in immunotoxicity was demonstrated for acetofenate using an in vitro macrophage cell line model (Zhao and Liu, 2009). However, in almost all previous studies, different endpoints were assessed independently, and consequently our present knowledge of enantioselectivity is rather disconnected and random. For instance, the direction of enantioselectivity in a given process appears to be essentially unpredictable. Therefore, studies aiming at inter-related mechanisms are imperatively needed for improving our overall understanding of environmental risks of chiral contaminants.
The close bidirectional interactions between the endocrine system and the immune system imply that modulation of the endocrine system by EDCs may also affect the immune system. Conversely, modulation of the immune system by EDCs, either directly or indirectly, may in turn affect the endocrine system (Selgrade, 2007, Filby et al., 2007). For example, natural (17β-estradiol) and synthetic (e.g., diethylstilbestrol) estrogens affect not only the endocrine system, but also the immune system (Chalubinski and Kowalski, 2006). It is well known that many man-made chiral chemicals are environmental EDCs, which include o,p′-DDT (McBlain et al., 1976), some polychlorinated biphenyls (PCBs) congeners (Rey deCastro et al., 2006), and synthetic pyrethroid insecticides (SPs) (Zhao et al., 2008). However, it is unknown if the linkage between endocrine disruption and immunotoxicity processes is reflected in enantioselectivity.
(Z)-cis-bifenthrin (cis-BF) is type I SPs which with a broad spectrum of insecticidal and acaricidal activity, which applied in both agricultural and urban environment. lambda-cyhalothrin (LCT) is a newer and type II pyrethroid insecticide wildly used for insects, fleas and ants controlling around households (Gan et al., 2008). In this study, we used these two typical SPs as model chiral contaminants and compared their enantioselectivity in immunotoxicity using macrophage cell line RAW264.7, and endocrine disruption activity in human breast carcinoma cell line MCF-7. Our aim was to probe if the common connections between the two processes would translate into a consistent enantioselectivity for chiral xenobiotics.
Section snippets
Chemicals and reagents
Lambda-cyhalothrin [LCT, (RS)-α-cyano-3-phenoxybenzyl (1R)-cis-3-(Z)-(2-chloro-3,3,3-trifluoroprop-1-enyl)-2,2-dimethylcyclopropanecarboxylate, purity of 98%] was obtained from Danyang Agrochemicals (Jiangsu, China). Analytical standard of (Z)-cis-bifenthrin [cis-BF, 99.5%, 2-methylbiphenyl-3-ylmethyl-(Z)-(1RS)-cis-3-(2-chloro-3,3,3-trifluoroprop-1-enyl)-2,2-dimethylcyclopropane carboxylate] was purchased from Sigma (St. Louis, MO, USA). All solvents (n-hexane, isopropanol, ethanol, and
Enantiomer separation and stability
Baseline separation of LCT and cis-BF enantiomers was achieved under the chromatographic conditions used in this study. Individual enantiomers with purity > 99% were derived and used in the subsequent bioassays. In previous studies, enantiomers of pyrethroids with a chiral α-carbon were found to undergo epimerization in alcohols and alcohol–water mixtures (Liu et al., 2005b). We carried out experiments to determine the stability of LCT enantiomers in ethanol and ethanol–water mixtures. This
Acknowledgements
This study was supported by the National Natural Science Foundations of China (No. 20837002, 20877071), the National Basic Research Program of China (No. 2009CB421603), and the Program for Changjiang Scholars and Innovative Research Team in Chinese Universities (No. IRT 0653).
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