Neurotoxicity of furan in juvenile Wistar rats involves behavioral defects, microgliosis, astrogliosis and oxidative stress.

ABSTRACT

Evidence suggests that furan, a widespread environmental and food contaminant, causes liver toxicity and cancer, but its implications in the brain are not well defined. We measured behavioral, glial, and biochemical responses in male juvenile rats exposed orally to 2.5, 5 and 10 mg/kg furan and vitamin E after 28 days. Furan-mediated hyperactivity peaked at 5 mg/kg and did not exacerbate at 10 mg/kg. Enhanced motor defect was also observed at 10 mg/kg. Furan-treated rats elicited inquisitive exploration but showed impaired spatial working memory. Without compromising the blood-brain barrier, furan induced glial reactivity with enhanced phagocytic activity, characterized by parenchyma-wide microglial aggregation and proliferation, which switched from hyper-ramified to rod-like morphology with increasing doses. Furan altered the glutathione-S-transferase-driven enzymatic and non-enzymatic antioxidant defence systems differentially and dose-dependently across brain regions. Redox homeostasis was most perturbed in the striatum and least disrupted in hippocampus/cerebellum. Vitamin E supplementation attenuated exploratory hyperactivity and glial reactivity but did not affect impaired working memory and oxidative imbalance. Overall, sub-chronic exposure of juvenile rats to furan triggered glial reactivity and behavioral deficits suggesting the brain's vulnerability during juvenile development to furan toxicity. It remains to be determined whether environmentally relevant furan concentrations interfere with critical brain developmental milestones.