Drug with antioxidant properties reverses cognitive impairment in mouse models of ageing

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An international team of researchers with participation of the UAB evaluated the protective effects of Calcium dobesilate (CaD), a drug with antioxidant properties, for the treatment of cognitive disorders in physiological ageing. Results demonstrated in an animal model that weight loss, anxiety-like and cognitive impairments were reversed by the administration of the drug, while also inhibiting the oxidative stress in their brains. The study has been published in Antioxidants.

29/04/2021

The senescence processes have not yet been fully defined, but it is well-documented that oxidative damage plays a crucial role. Oxidative stress caused by the abnormal accumulation of reactive oxygen species (ROS) in the brain has also been associated with anxiety and cognitive disorders in older people.
 
To investigate the mechanisms involved and to screen the preventive and therapeutical potential of compounds and drugs, an international team of researchers, with the participation of Lydia Giménez-Llort, full professor of the Psychiatry and Forensic Medicine Department and member of the UAB Institut de Neurociències, treated male mice with D-galactose, a sugar that recreates the accumulation of ROS occurring in ageing. Using these animal models of accelerated ageing, they analyzed the capacity of CaD, a drug commonly used for diabetic retinopathy and chronic venous insufficiency, to treat the cognitive and neuropsychiatric problems and underlying oxidative stress in the brain.

The drug, which normally cannot cross the blood-brain barrier, would be able to do it when the brain’s permeability is increased due to ageing, decreasing damaged vessels’ permeability and reducing the concentration of inflammatory mediators. Researchers led by Iman Fatemi Lab, from the Kerman University of Medical Sciences in Iran, now demonstrated that CaD also reduces oxidative stress, reversing cognitive deficits and anxiety-like behaviours. “This is very important because these are psychological and biological hallmarks of ageing and their rescue in this animal model mimicking ageing suggests a drug repurposing with translational potential”, explains Lydia Giménez-Llort.

Since this drug has already been clinically approved for the treatment of micro-vascular damage-related diseases, and it has few side effects, its repurposing may represent an interesting new tool to prevent and treat cognitive impairment in the older people.

Article: Hakimizadeh, E.; Zamanian, M.; Giménez-Llort, L.; Sciorati, C.; Nikbakhtzadeh, M.; Kujawska, M.; Kaeidi, A.; Hassanshahi, J.; Fatemi, I. Calcium Dobesilate Reverses Cognitive Deficits and Anxiety-Like Behaviors in the D-Galactose-Induced Aging Mouse Model through Modulation of Oxidative Stress. s. Antioxidants 2021, 10, 649. https://www.mdpi.com/2076-3921/10/5/649