Neuroprotective responses of quercetin in regulation of biochemical, structural, and neurobehavioral effects in 28-day oral exposure of iron in rats.

Background: Iron is one of the essential metals that functions as a cofactor in various biological cascades in the brain. However, excessive iron accumulation in the brain may lead to neurodegeneration and may show toxic effects. Quercetin, a pigment flavonoid compound, has been proven to be a potent antioxidant and anti-inflammatory that can inhibit lipid peroxidation during metal-induced neurotoxicity. Although iron-induced neuroinflammation and neurodegeneration have been reported in many studies, but the proof for its exact mechanisms needs to be explored.

Purpose: The key target of the study was to explore the neuroprotective effect of quercetin after oral exposure of iron in rats and explore its underlying molecular mechanisms.

Results: The outcomes of the study have shown that oral exposure to ferrous sulfate may modulate behavioral paradigms such as locomotor activity, neuromuscular coordination, and increased anxiety level. The pro-inflammatory cytokines (TNF-α, IL-1β and IL-6), apoptotic protein (caspase 3), beta-amyloid and phosphorylated tau were found to be increased on iron exposure. Also, the expressions of ferritin heavy and light chain, BACE-1 and GFAP expressions were altered. These behavioral, structural, and biochemical alterations in the brain were significantly and dose-dependently reversed by treatment with quercetin.

Conclusion: The current study provides a fundamental understanding of molecular signaling pathways, and structural proteins implicated in iron-induced neurotoxicity along with the ameliorative effects of quercetin.