Mitochondrial dysfunction due to in vitro exposure to atrazine and its metabolite in striatum

KARADAYIAN, ANALÍA G.; PAEZ, BÁRBARA; BUSTAMANTE, JUANITA; LORES-ARNAIZ, SILVIA; CZERNICZYNIEC, ANALÍA

JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY

JOHN WILEY & SONS INC

Año: 2023

1095-6670

Atrazine (2-chloro-4-ethylamino-6-isopropylamino-s-triazine) has been described as a potential toxic for dopaminergic metabolism both in vivo and in vitro. Its main metabolite diamino-chloro triazine (DACT) has been shown to achieve higher levels in brain tissue than atrazine. The aim of this study was to evaluate the in vitro effects of atrazine and DACT on striatal mitochondrial function, active oxygen species generation, and nitric oxide (NO) content. Incubation of mitochondria with atrazine (10 µM) was not able to modify oxygen consumption. However, a 50% increase in malate-glutamate state 4 respiratory rates was observed after DACT treatment (100 µM) without changes in respiratory state 3. Atrazine was able to inhibit complex I–III activity by 30% and DACT induced a tendency to decrease by 17% in the striatum. Regarding reactive oxygen species (ROS), DACT increased H2O2 production by 43%. Also, superoxide anion levels were higher (14%) after atrazine exposure than in control mitochondria. Incubation of striatal mitochondria with atrazine and DACT induced membrane depolarization by 15% and 19%, respectively. Also, atrazine increased NO content by 10% but no significant changes were observed after exposure of mitochondria to DACT. Glutathione peroxidase activity was inhibited (56%) by DACT and atrazine inhibited superoxide dismutase activity by 60%. Also, cardiolipin oxidation (15%) was observed after atrazine treatment. Summing up, the obtained results suggest that in vitro atrazine and DACT induce ROS production affecting striatal mitochondrial function. The atrazine effects would be attributed to a direct effect on the mitochondrial respiratory chain and superoxide dismutase activity while DACT appears to disturb glutathione-related enzyme system.