Investigation of The Relationship between The Pesticide Fluopyram and Parkinson's disease

Parkinson's disease (PD) is a neurodegenerative disease defined as a shaky stroke. It is clinically characterized by; resting tremor, cogwheel rigidity, bradykinesia, and postural reflex impairment. It is also pathologically characterized by Lewy bodies (LBs) and formed by the loss of dopaminergic neurons in the Substantia nigra pars compacta (SNpc) region of the brain and the accumulation of Alpha-Synuclein (alpha-Syn) proteins. Pesticides are the hugest risk factor of PD. They cause the formation of PD by using different mechanisms. They also permanently disrupt the function of the electron transport complex (ETC) located in the mitochondria. Researches show that the pesticide Rotenone (ROT) causes PD in vivo and in vitro conditions by inhibiting mitochondrial complex I and causing oxidative stress. Fluopyram (Flu) is a frequently used pesticide that causes mitochondrial toxicity like ROT. When literature is searched, it makes one think about a connection with PD. it seems that there is no available study on Flu and PD. Flu is one of the fungicides utilized in Isparta city at a high rate for all planting types. The Flu is a mitochondrial complex II inhibitor. The inhibition of mitochondrial complexes is the main pathway in the PD mechanism, therefore complex II inhibitor pesticide may lead to the same result. In this context, we created a Parkinson's model in mice with ROT and compare the result of Flu with this ROT to be sure whether that lead to Parkinson's or not. Swiss albino male and female mice were the testing animals of our study. Positive control (ROT Parkinson model, 1 mg/kg/day), negative control (Solvent only, DMSO), and Flu (0.5,1 and 2 mg/kg/day) were administrated to mice daily doses subcutaneously (SC). The experiment got completed after 21 days. Motor Function Test, Histochemical and Immunohistochemical Studies, Comet assay, and quantitative real-time PCR (qRT-PCR) were utilized in the study as well. In our results, no statistically significant changes were observable in animal weights in all groups. In the motor function test, a significant decrease in the ROT group was observable, On the other hand, a significant decrease was detected specifically in the Flu value which was applied at high doses. When the brain tissues that belong to the ROT and Flu tested groups got examined, all-important structural changes such as LBs got observed in the SN. When brain tissues belonging to ROT and Flu groups were examined in alpha-Syn immunohistochemical staining, more positive markings were observable. When the brain tissues belonging to the ROT and Flu groups were examined in Tyrosine hydroxylase (TH) immunohistochemical staining, fewer positive markings were observed. ROT has been found to cause DNA damage in blood and brain tissues. It has been determined that groups with Flu applied in the brain do not have DNA damage. ROT was observed to increase SNCA mRNA expression levels while decreasing TH and DJ-1 mRNA expression levels. Comparing the Flu and ROT results, SNCA mRNA expression levels increased but were not significant. With the detection of decreased TH and DJ-1 mRNA expression levels, the difference was shown in our ROT results. In conclusion, The study results have proved that in mice Flu's induce of PD phenotype depends on Flu doses. It is recommended to do more research with Flu especially in high doses and with different methods.