Influence of pyrethroids and piperonyl butoxide on the Ca 2+-ATPase activity of rat brain synaptosomes and leukocyte membranes

Department of Pharmacology, The Panum Institute, University of Copenhagen, Blegdamsvej 3, DK-2200 Copenhagen N, Denmark.
International Immunopharmacology (Impact Factor: 2.47). 03/2005; 5(2):263-70. DOI: 10.1016/j.intimp.2004.09.030
Source: PubMed


Pyrethroids are widely used insecticides of low acute toxicity in mammals but the consequences of long-term exposure are of concern. Their insecticidal action is related to neurotoxicity and, in addition, there are indications of mammalian immunotoxicity. In order to clarify structure-activity relationships of the membrane interactions of pyrethroids, the present study compared the influence of selected pyrethroids, i.e. permethrin and the more water soluble esbiol (S-bioallethrin), both type I, and cyfluthrin, type II, on the Ca(2+)-ATPase activity of rat brain synaptosomes and peritoneal leukocyte membranes. The pyrethroids were tested alone as well as mixed with the enhancing substance piperonyl butoxide (PBO) at concentration ratios of 1:5 and 1:10. At the highest concentration tested, permethrin (10 microM) alone inhibited the ATPase activity of leukocyte membranes by 20%, whereas the synaptosomes were affected less. Esbiol and cyfluthrin alone did not affect either membrane preparation significantly, whereas PBO (50 microM) alone caused 10-15% inhibition. Mixtures of either pyrethroid with PBO inhibited the ATPase activity of both types of membranes (up to 40% inhibition) in a synergistic manner, which always tended to be supra-additive. With esbiol a true potentiation took place. The synergistic interaction between pyrethroid and PBO was most apparent with mixtures of a concentration ratio of 1:5. The ATPase activity of leukocyte membranes tended to be more susceptible to inhibition than that of synaptosomes. The results are in accordance with the assumption that the mammalian toxicity of pyrethroids can be ascribed to a general disturbance of cell membrane function in neuronal tissue. The results indicate that it may also be the case in the immune apparatus.

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    • "However , some widely used pyrethroids are comparable to many organophosphorus insecticides in terms of toxicity. Their insecticidal action is related to neurotoxicity ascribed to a general disturbance of cell membrane function in neuronal tissue (Grosman and Diel, 2005). Pyrethroids are capable of interacting with the human estrogen receptor (McCarthy et al., 2006) and thus present a risk to human health. "
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    ABSTRACT: Concerns about pesticide exposure through food consumption have increased during the past several years. Pyrethroids are applied as insecticides throughout the world. Human metabolism of pyrethroids results in urinary metabolites that are suitable for biological monitoring. The objective of our study was to investigate the relation between food consumption and urinary levels of 3-phenoxybenzoic acid (3-PBA), a general metabolite of pyrethroids, in a non-occupational exposed adult population from the IDI-IRCCS, Rome, Italy. Information on socio-demographic characteristics, smoking, diet and self-reported household pesticide exposure was collected. Urinary 3-PBA level of each subject was measured and adjusted by urinary creatinine. We found that people consuming both raw and cooked vegetables five times weekly or more had higher mean levels of 3-PBA in urine (1.03 μg/g creatinine versus 0.52 μg/g creatinine; p=0.009 and 0.99 μg/g creatinine versus 0.58 μg/g creatinine; p=0.01 respectively) than subjects consuming less than five times weekly. In a multivariate model, after adjusting for age, sex, BMI, smoking and household insecticide exposure, high intake of raw vegetables (OR: 5.31; 95%CI: 1.32- 21.3) and high intake of cooked vegetables, in particular cruciferous (OR: 4.67; 95%CI: 1.07- 20.5) and leafy vegetables (OR: 6.88; 95%CI: 1.50- 31.7), were associated with high urine 3-PBA levels (⩾ 0.70. μg/g creatinine). The results of this study suggest that part of the variation in pyrethrois intake is explained by vegetable intake.
    Full-text · Article · Nov 2012 · Food and chemical toxicology: an international journal published for the British Industrial Biological Research Association
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    • "There is an increasing trend in the use of PYRs indoors, as a result of the federally mandated phase-out of most residential uses of organophosphate (OP) pesticides, particularly chlorpyrifos and diazinon [2] [3]. Although PYRs exhibit relatively lower mammalian toxicity than the OP pesticides, some studies have identified PYRs as potential human neurotoxicants that may cause developmental neurotoxic and immunotoxic effects [4] [5] [6]. One of the commonly used PYRs, permethrin, is reported to have weak endocrine disrupting properties [7]. "
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    ABSTRACT: An efficient and reliable analytical method was developed for the sensitive and selective quantification of pyrethroid pesticides (PYRs) in house dust samples. The method is based on selective pressurized liquid extraction (SPLE) of the dust-bound PYRs into dichloromethane (DCM) with analysis by gas chromatography/mass spectrometry. Various adsorbents and combinations of extraction solvents and temperatures were evaluated to achieve a high-throughput sample preparation that eliminates the post-extraction cleanup step. The final method used sulfuric acid-impregnated silica (acid silica) and neutral silica together in the extraction cell with the dust sample to provide both extraction and cleanup simultaneously. The optimal ratio of dust/acid silica/silica was 1:0.8:8. The extraction was performed at 2000 psi, at 100°C with DCM for 5 min in three cycles. Method precision and accuracy were evaluated by the analysis of triplicate aliquots of the dust samples and the samples fortified with the target PYRs. The accuracy measured as the recoveries of the PYRs in the fortified samples ranged from 85% to 120%. The precision measured as the relative standard deviation of replicate samples was within ±25%. The SPLE method was applied to 20 house dust samples collected from households that participated in two field studies regarding exposures to pesticides and other pollutants. Similar concentrations of target PYRs were obtained for the SPLE and a stepwise extraction/cleanup procedure. The SPLE procedure reduces organic solvent consumption and increases the sample throughput when compared with a traditional stepwise extraction and cleanup procedure. This study demonstrates that the SPLE procedure can be applied to complex dust matrices for analysis of PYRs for large scale exposure or environmental monitoring studies.
    Full-text · Article · Oct 2012 · Analytica chimica acta
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    • "The immunotoxic effects of chemicals include effects at the cellular level and on the organs of the immune system. Several pyrethroids have been reported displaying cytotoxicity in other cell models because of oxidative damage (Grosman and Diel, 2005), "
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    ABSTRACT: The increasing release of chiral chemicals into the environment dictates attention to a better understanding of enantioselectivity in their human and ecotoxicological effects. Although enantioselectivity has been considered in many recent studies, there is little effort for discerning the connection between different processes, and as such, our current knowledge about chiral contaminants is rather scattered and incoherent. In this study, we simultaneously evaluated enantioselectivity of two chiral pesticides, lambda-cyhalothrin (LCT) and (Z)-cis-bifenthrin (cis-BF), in immunotoxicity to macrophage cells (RAW264.7), and endocrine disruption activity in human breast carcinoma cell line MCF-7. Analysis of cell proliferation, cell viability, apoptosis, and receptor gene expression showed significant differences between the enantiomers of LCT or cis-BF in estrogenic potential and immunocytotoxicity. The selectivity in these effects consistently followed the same direction, with (-)-LCT or 1S-cis-BF displaying a greater activity than its counterpart. The consistency was attributed to interplaying mechanisms in the closely interacting immune and endocrine systems. The underlying interplays suggest that other chiral xenobiotics may also show a directional enantioselectivity in immunotoxicity and endocrine toxicity. Given that many biological processes are inter-related, enantioselectivity may follow specific patterns that can be revealed via integrative assessments as demonstrated in this study.
    Full-text · Article · May 2010 · Environmental Pollution
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