Cypermethrin induces neurotoxicity via inhibition of glial cell viability and apoptosis initiation

Abstract

The progress in agricultural productivity is accompanied by the increase in the global application of pesticides. Moreover, the number of different pesticides used is growing permanently all over the world. Several types of pesticides are effective tools to suppress the propagation of insects, bacteria, and fungi. However, they could correlate with toxicity for other non-targeted organisms including mammalian and humans. Neurotoxicity is considered to be the most detrimental effect of pesticides given the ecotoxicology studies of the environmental pollution consequences for the last decades. Exposure to neurotoxic pesticides can induce multiple harmful disturbances in the deregulation of vital molecular pathways, cellular response, and programmed cell death initiation as well as lead to a decline in the functioning of the central neural system (CNS). All of them are potent in inhibiting the adaptation mechanisms and viability of vertebrate populations. The pyrethroids are the most total used group of pesticides. This study of the neurotoxic effects of pyrethroids aimed to contribute to assessing the risk rate in the application of compromised chemicals in agriculture production. Glial cells are the prevailing population in the CNS. Measurement of the cytotoxic effect of pollutants can be assessed by their neurotoxicity in glial cell culture. In the present study, we detected glioma U251 cells' viability, oxidative stress indices, and a mitochondria-associated marker of apoptosis to evaluate the molecular mechanism of cypermethrin neurotoxicity. Obtained results have shown that 2 and 5 μg/ml doses of cypermethrin inhibited glioma U251 cell viability (p<0.05) and increased an oxidative stress level. Contrary, the dose of cypermethrin 1 μg/ml did not induce statistically significant both cell viability and oxidative stress. However, 2 and 5 μg/ml doses of cypermethrin exposure induced cytochrome C release to cytosol in a dose-dependent manner that is a marker of apoptosis initiation. Thus, the neurotoxic effect of pyrethroids can be mediated by the mitochondrial-dependent apoptotic pathway activation via cytochrome C release.