From the Cover: Vulnerability of C6 Astrocytoma Cells After Single-Compound and Joint Exposure to Type I and Type II Pyrethroid Insecticides.
A primary mode-of-action of all pyrethroid insecticides (PYRs) is the disruption of the voltage-gated sodium channel electrophysiology in neurons of target pests and nontarget species. The neurological actions of PYRs on non-neuronal cells of the nervous system remain poorly investigated. In the present work, we used C6 astrocytoma cells to study PYR actions (0.1-50 μM) under the hypothesis that glial cells may be targeted by and vulnerable to PYRs. To this end, we characterized the effects of bifenthrin (BF), tefluthrin (TF), α-cypermethrin (α-CYP), and deltamethrin (DM) on the integrity of nuclear, mitochondrial, and lysosomal compartments. In general, 24- to 48-h exposures produced concentration-related impairment of cell viability. In single-compound, 24-h exposure experiments, effective concentration (EC)15s 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT assay) were computed as follows (in μM): BF, 16.1; TF, 37.3; α-CYP, 7.8; DM, 5.0. We found concentration-related damage in several C6-cell subcellular compartments (mitochondria, nuclei, and lysosomes) at ≥ 10-1μM levels. Last, we examined a mixture of all PYRs (ie, Σ individual EC15) using MTT assays and subcellular analyses. Our findings indicate that C6 cells are responsive to nM levels of PYRs, suggesting that astroglial susceptibility may contribute to the low-dose neurological effects caused by these insecticides. This research further suggests that C6 cells may provide relevant information as a screening platform for pesticide mixtures targeting nervous system cells by expected and unexpected toxicogenic pathways potentially contributing to clinical neurotoxicity.
Laboratorio de Toxicología de Mezclas Químicas.|Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Argentina.|IQUIBICEN-Argentina National Research Council (CONICET).
Delfina M
DM
Romero
Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Argentina.|Laboratorio de Neuroepigenética.
Bruno G
BG
Berardino
Laboratorio de Toxicología de Mezclas Químicas; mjwolansky@qb.fcen.uba.ar.|Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Argentina.|IQUIBICEN-Argentina National Research Council (CONICET).
Marcelo J
MJ
Wolansky
Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Argentina.|IQUIBICEN-Argentina National Research Council (CONICET).|Laboratorio de Disfunción Celular en Enfermedades Neurodegenerativas y Nanomedicina.
Mónica L
ML
Kotler
D000818:Animals; D001254:Astrocytoma / Q000473:pathology*; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D007306:Insecticides / Q000633:toxicity*; D008856:Microscopy, Fluorescence; D011722:Pyrethrins / Q000633:toxicity*; D051381:Rats; D013347:Subcellular Fractions / Q000378:metabolism
D007306:Insecticides; D011722:Pyrethrins
C6 cells; cell death.; cellular damage; pyrethroids