Objective: 3-phenoxybenzoic acid (3-PBA) is a metabolite of Fenpropathrin (FEN). The emphasis of this paper is on the relationship between 3-PBA and Dopaminergic Degeneration.

Background: FEN is one of pyrethroid insecticides, which widely used in agriculture to control insect pests. In our previous research, we found FEN can cause symptoms of Parkinson’s disease (PD) when people exposed in a certain concentration of this pesticide. Up to present, many studies have identified that FEN would rapidly metabolized when absorbed into the body, the acid moiety turn to be 2,2,3,3-tetramethyl cyclopropane carboxylic acid (FC), and the alcohol moiety turn to be 3-phenoxybenzoic acid (3-PBA). 3-PBA is not only the metabolite of FEN, but also the metabolite of other principal pyrethroids. The bioaccumulation of 3-PBA would increase over time when body exposed in most pyrethroids because of its hardly metabolization.

Method: In vitro and in vivo experiment was combined in our study. In this study, we found that FC can not through blood brain barrier (BBB) of mice when we detected these three substances by Liquid chromatography-tandem mass spectrometry / mass spectrometry (LC-MS/MS). Therefore, we choose 3-PBA as the objective substance. At the same concentration, we observed that 3-PBA can cause more significant features than FEN in pathologic and pathogenetic manifestation of PD.

Results: In vitro, we found Lewy body-associated proteins aggregation in cultured SH-SY5Y cells treat with 3-PBA and Lewy body-like intracytoplasmic inclusions formation appeared likewise. Additionally, in rodent animals, we choose intraperitoneal (i.p) for injection of FEN and 3PBA. After 60 days of i.p, compared with the FEN groups, 3PBA group exhibited lower number of pokes in rotarod test, more markedly degeneration of dopaminergic interneurons, more obviously decrease of tyrosine hydroxylase (TH) and vesicular monoamine transporter 2 (VMAT2) immunoreactivity in substantia nigra and striatum.

Conclusion: The result we obtained demonstrate that 3-PBA is the probably major contributor to dopaminergic degeneration in the condition of FEN exposure, even in other pyrethroids exposure.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/the-influence-of-3-phenoxybenzoic-acid-in-dopaminergic-degeneration/