Increased susceptibility of mitochondria isolated from frontal cortex and hippocampus of vitamin A-treated rats to non-aggregated amyloid-β peptides 1-40 and 1-42.

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.