VULNERABILITY OF C6 ASTROCYTOMA CELLS AFTER SINGLE-COMPOUND AND JOINT EXPOSURE TO TYPE I AND TYPE II PYRETHROID INSECTICIDES

BERARDINO BG; ROMERO D; KOTLER ML; WOLANSKY MJ

TOXICOLOGICAL SCIENCES

OXFORD UNIV PRESS

Lugar: Oxford; Año: 2017 vol. 155 p. 196 - 212

1096-6080

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, 24-48 h exposures produced concentration-related impairment of cell viability. In single-compound, 24-h exposure experiments, EC15s (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, lysosomes) at ≥10-1μM levels. Last, we examined a mixture of all PYRs (i.e., 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.