Repeated co-exposure to aflatoxin B 1 and aspartame disrupts the central nervous system homeostasis: Behavioral, biochemical, and molecular insights.

Several studies demonstrated the toxicity of aspartame (ASP) and aflatoxin B 1 (AFB 1 ) in preclinical models. Although the majority of these reports assessed the toxic effects of each substance separately, their concomitant exposure and hazardous consequences are scarce. Importantly, the deleterious effects at the central nervous system caused by ASP and AFB 1 co-exposure are rarely addressed. We evaluated if concomitant exposure to AFB 1 and ASP would cause behavioral impairment and alteration in oxidative status of the brain in male rats. Animals received once a day for 14 days AFB 1 (250 µg/kg, intragastric gavage [i.g.]), ASP (75 mg/kg, i.g.), or both substances (association). On day 14, they were subjected to behavioral evaluation, and biochemical and molecular parameters of oxidative status were measured in the cerebral cortex and hippocampus. In the open field test, AFB 1 and combination treatments modified the motor, exploratory, and grooming behavior. In the splash test, all treatments caused a reduction in grooming time compared to the control group. An increase in thiobarbituric acid-reactive substances content induced by AFB 1 and combination treatments was observed. The antioxidant defenses (vitamin C, nonprotein sulfhydryl, and ferric reducing antioxidant power) were impaired in all groups compared to control. Regarding molecular evaluation, mitochondrial superoxide dismutase-2 immunoreactivity decreased after AFB 1 or ASP exposition in the hippocampus. Thus, co-exposure to ASP and AFB 1 was potentially more toxic because it aggravated behavioral impairments and oxidative status disbalance in comparison to the groups that received only ASP or AFB 1 . Therefore, our data suggest that those substances caused a disruption in brain homeostasis.