In vitro effects of atrazine and diamino-chloro triazine on mitochondrial functionality and nitric oxide metabolism in striatum

BARBARA PAEZ; ANALIA CZERNICZYNIEC; SILVIA LORES ARNAIZ; ANALIA G. KARADAYIAN

Mar del Plata

Congreso; LXIV Reunión Anual de la Sociedad Argentina de Investigación Clínica (SAIC); 2019

Sociedad Argentina de Investigación Clínica

Atrazine (ATZ) is an herbicide frequently used in Argentina and it is metabolized primarily by cytochrome P450. Diamino-chloro triazine (DACT) is the main metabolite detected in plasma and rat urine after in vivo atrazine exposure. Considering that both ATZ and DACT can cross the blood brain barrier, the aim of this work was to evaluate the in vitro effect of those compounds on striatal mitochondrial function and nitric oxide (NO) metabolism. Striatal mitochondria were isolated from SD rats (180-200 g) and exposed to 10 µM ATZ or 100 µM DACT. Respiratory rates, H2O2 production, respiratory complexes activity, monoamine oxidase, membrane potential, superoxide anion production and NO levels were evaluated. Results showed that ATZ did not modify respiratory rates. However, DACT increased O2 consumption in state 4 (55%) and decreased respiratory control in striatal mitochondria. Production of H2O2 was increased after exposure of both ATZ (25%) and DACT (38%), probably due to the inhibition of complex I-III activity (30% and 17%, respectively). No significant changes were observed in the activity of complex II-III or monoamine oxidase in striatal mitochondria in the presence of the herbicide or its metabolite. The results showed a depolarization of 15% and 19% in striatal mitochondria exposed to ATZ and DACT, respectively. The evaluation of superoxide anion production showed a 13% increase after atrazine treatment and no significant changes were observed in the presence of DACT. Meanwhile, an increase in NO levels (11%) was observed after exposure of striatal mitochondria to atrazine, without changes in those exposed to DACT.Obtained results suggested that in vitro ATZ and DACT affect striatal mitochondrial function and nitric oxide metabolism through different mechanisms.