Fenpropathrin, a Widely Used Pesticide, Causes Dopaminergic Degeneration

Abstract

Fenpropathrin is one of the widely used pyrethroids in agriculture and household and also reported to have neurotoxic effects in rodent models. In our Parkinson’s disease (PD) clinic, there was a unique patient with a history of daily exposure to fenpropathrin for 6 months prior to developing Parkinsonian symptoms progressively. Since whether fenpropathrin is related to any dopaminergic degeneration was unknown, we aimed in this study to evaluate the neurotoxic effects of fenpropathrin on the dopaminergic system and associated mechanisms in vitro and in vivo. In cultured SH-SY5Y cells, fenpropathrin caused cell death, reactive oxygen species generation, Lewy body-associated proteins aggregation, and Lewy body-like intracytoplasmic inclusions formation. In rodent animals, two different injections of fenpropathrin were used for administrations, intraperitoneal (i.p), or stereotaxical (ST). The rats exhibited lower number of pokes 60 days after first i.p injection, while the rats in ST group showed a significant upregulation of apomorphine-evoked rotations 60 days after first injection. Dcreased tyrosine hydroxylase (TH) and vesicular monoamine transporter 2 (VMAT2) immunoreactivity, while increased dopamine transporter (DAT) immunoreactivity were observed in rats of either i.p or ST group 60 days after the last exposure to fenpropathrin. However, the number of TH-positive cells in the substantia nigra was more reduced 120 days after the first i.p injection than those of 60 days. Our data demonstrated that exposure to fenpropathrin could mimic the pathologic and pathogenetic features of PD especially in late onset cases. These results imply fenpropathrin as a DA neurotoxin and a possible environmental risk factor for PD.

Environmental Exposures and Parkinson’s Disease

“…Pyrethroids are a newer class of insectides often contained in household insecticides and mosquito repellants. Animal studies have reported the ability of pyrethroids to indirectly increase dopamine transporter-mediated dopamine uptake [ 93 ] and thus cause indirect apoptosis of dopaminergic cells [ 94 , 95 ]. However, this area requires further study, as there is little specific human data besides the general finding that pesticide exposure, including pyrethroids, is associated with PD [ 73 ].…”

The ameliorative potential of the ethanol extract of the plant Ocimum basilicum on Biomphalaria alexandrina snails exposed to the insecticide Bestacid

“…Raj and Joseph (2015) stated that chronic exposure of Oreochromis mossambicus fish to the sub-lethal concentration of acetamiprid 5.99 ppm (LC50) increased activity of lactate dehydrogenase in their liver, brain and gill tissues during all the exposure periods when compared with the control. 10% Fenpropathrin is one of the widely used pyrethroid insectides that had neurotoxic effects in rodent models (Xiong et al, 2016). It was used to control many species of mites (except rust mites) and insects (e.g.…”

Fenpropathrin induces degeneration of dopaminergic neurons via disruption of the mitochondrial quality control system

“…Although previous studies in cell lines and in rats have previously demonstrated Fen-induced neurodegeneration 5,29 , the underlying mechanisms of this phenomenon have remained unclear. In our present study, we focused on the effect of Fen on mitochondria, because considerable evidence has shown that mitochondria play a critical role in the progression of neurodegeneration.…”

“…With the increasing use of these compounds, the risk of human exposure to Pyr residues in vegetables, fruits, well water, and carpets soaked to eliminate insect pests in homes has risen and potential side effects of Pyr exposure have received increased attention. Many studies have indicated that Pyr has neurotoxic effects and leads to the degeneration of neurons via disturbing the balance between oxidants and antioxidants in mouse brains, as well as by affecting the expression of dopamine transporter and/or vesicular monoamine transporter 2 in DA neurons [4][5][6] . Using a previous case study as a correlational example in humans, a man who had consumed fenpropathrin (Fen) derived from Fen-poisoned fish for half a year was diagnosed with parkinsonism in China 5 .…”