Atrazine and its major metabolite (DACT) increase striatal mitochondrial H2O2 levels through different mechanisms.

KARADAYIAN, AG; PAEZ, B; CZERNICZYNIEC, A; LORES ARNAIZ, S

Buenos Aires

Congreso; IV International Congress in Translational Medicine; 2018

Facultad de Farmacia y Bioquímica, UBA

Atrazine and its major metabolite (DACT) increase striatal mitochondrial H2O2 levels through different mechanisms. Paez,B.; Karadayian, A.; Lores Arnaiz, S.; Czerniczyniec, A.Instituto de Bioquímica y Medicina Molecular (UBA-CONICET), FFyB, UBA. Junín 956, 2ª, C1113AAD, Buenos Aires, Argentina Atrazine (ATZ), a chlorotriazine herbicide, is frequently found in ground, surface, and water due to its widespread use and relative. Human exposure to this herbicide is a concern as ATZ or its metabolites have been detected in the urine of pesticide applicators and their families. This study sought to determine the effect of in vitro exposure to ATZ or its major mammalian metabolite diaminochlorotriazine (DACT) on hydrogen peroxide (H2O2) production. Also, we evaluated the mechanism involved in this process.Striatal intact mitochondria and submitochondrial membranes from SD rats (180-200 g) were incubated with different ATZ and DACT concentrations for 1 minute. ATZ and DACT concentrations tested are related to the maximal brain tissue levels detected after exposure of mice or rats to single oral dose of ATZ (5?250 mg/kg). Both ATZ (10 µM) and DACT (100 µM) increased H2O2 production by 30 % in striatal mitochondria. In order to elucidate the mechanism involved, MAO and mitochondrial respiratory complex I activities were measured. MAO activity was induced by ATZ (1.1 fold) and DACT (82%). However, inhibition of striatal complex I activity only was observed after the incubation of submitochondrial membranes with 10 µM ATZ.Cortical mitochondria were also incubated with ATZ and DACT but none of the mitochondrial parameters evaluated were affected. Besides, O2 consumption in striatal intact mitochondria was determined. Results showed that ATZ decreased state 4 respiratory rates by 27%, but not significant changes were observed after DACT treatment. State 3 respiratory rates were not affected by the herbicide and its metabolite.This work provides evidence that in our study conditions, ATZ and DACT raise striatal H2O2 levels probably by different mechanisms.