Objective: Vitamin A is a redox-active molecule and its inadvertent utilisation as a preventive therapy against ageing or neurodegeneration has become a harmful habit among humans at different ages. Mitochondrial dysfunction and redox impairment may be induced by vitamin A supplementation experimentally. Nonetheless, it is still not clear by which mechanisms vitamin A elicits such effects. Then, we performed this investigation to analyse whether mitochondria isolated from frontal cortex and hippocampus of vitamin A-treated rats are more sensitive to a challenge with amyloid-β (Aβ) peptides 1–40 or 1–42.

Methods: Adult Wistar rats received vitamin A at 1000–9000 IU/kg/day orally for 28 days. Then, mitochondria were isolated and the challenge with Aβ peptides 1–40 or 1–42 (at 0.2 or 0.1 μM, respectively) for 10 min was carried out before mitochondrial electron transfer chain enzyme activity, superoxide anion radical (O2−•) production and 3-nitrotyrosine content quantification.

Results: Mitochondria obtained from vitamin A-treated rats are more sensitive to Aβ peptides 1–40 or 1–42 than mitochondria isolated from the control group, as decreased mitochondrial complex enzyme activity and increased O2−• production and 3-nitrotyrosine content were observed in incubated mitochondria isolated from vitamin A-treated rats.

Conclusion: These data suggest that oral intake of vitamin A at clinical doses increases the susceptibility of mitochondria to a neurotoxic agent even at low concentrations.