TY - JOUR
T1 - Pro-apoptotic effects of low doses of dimethoate in rat brain
AU - Arnal, Nathalie
AU - Morel, Gustavo
AU - Marra, Carlos A.
AU - Astiz, Mariana
N1 - Funding Information:
This work was supported by grants from Agencia Nacional de Promoción Científica y Tecnológica ( PICT 2014-1549 ) and Consejo Nacional de Investigaciones Científicas y Técnicas ( CONICET PIP0203 ).
Publisher Copyright:
© 2018 Elsevier Inc.
Copyright:
Copyright 2019 Elsevier B.V., All rights reserved.
PY - 2019/1/15
Y1 - 2019/1/15
N2 - Dimethoate (DMT), a widely used Organophosphorous insecticide, was administered for 5 weeks (sub-chronic) at low dose (15 mg/kg b.w.) to male Wistar rats with the aim to simulate potential exposure to pesticide residues in food and water. The induction of cell death programs was investigated in two brain regions, cortex (Cx) and substantia nigra (SN), after the exposure period. We found that DMT increased cytochrome C (CytC) release from mitochondria, the Bax/Bcl-2 ratio, the activity of caspase-3 and calpains, in both brain regions compared to VEH injected ones. DMT treatment induced oxidative damage of lipids with a consequent enrichment in saturated over unsaturated fatty acids. However, the activity of mitochondrial respiratory complexes was not affected by DMT treatment. The activation of the pro-apoptotic pathway can be correlated with a decrease of TH-immunoreactive neurons in SN, comparable to the reduction observed in this cell population by aging. The results of this work contribute to understand the toxic mechanism of DMT and the possible etiological role that residues of this insecticide, might play in neurodegenerative diseases.
AB - Dimethoate (DMT), a widely used Organophosphorous insecticide, was administered for 5 weeks (sub-chronic) at low dose (15 mg/kg b.w.) to male Wistar rats with the aim to simulate potential exposure to pesticide residues in food and water. The induction of cell death programs was investigated in two brain regions, cortex (Cx) and substantia nigra (SN), after the exposure period. We found that DMT increased cytochrome C (CytC) release from mitochondria, the Bax/Bcl-2 ratio, the activity of caspase-3 and calpains, in both brain regions compared to VEH injected ones. DMT treatment induced oxidative damage of lipids with a consequent enrichment in saturated over unsaturated fatty acids. However, the activity of mitochondrial respiratory complexes was not affected by DMT treatment. The activation of the pro-apoptotic pathway can be correlated with a decrease of TH-immunoreactive neurons in SN, comparable to the reduction observed in this cell population by aging. The results of this work contribute to understand the toxic mechanism of DMT and the possible etiological role that residues of this insecticide, might play in neurodegenerative diseases.
UR - http://www.scopus.com/inward/record.url?scp=85057483879&partnerID=8YFLogxK
U2 - 10.1016/j.taap.2018.11.013
DO - 10.1016/j.taap.2018.11.013
M3 - Journal articles
C2 - 30502393
AN - SCOPUS:85057483879
SN - 0041-008X
VL - 363
SP - 57
EP - 63
JO - Toxicology and Applied Pharmacology
JF - Toxicology and Applied Pharmacology
ER -
