Abstract
The long-term treatment of mice with D-galactose (D-gal) induces the overproduction of reactive oxygen species (ROS) and is a well-accepted experimental model of oxidative stress-linked cognitive disorders in physiological aging. Calcium dobesilate (CaD, Doxium®) is an established vasoactive and angioprotective drug commonly used for the clinical treatment of diabetic retinopathy and chronic venous insufficiency. It has antioxidant properties and controls vascular permeability. In the current study, we evaluated the protective effects of CaD (50 and 100 mg/kg/day p.o.) in male mice treated with D-gal (500 mg/kg/day p.o.) for six weeks. Results demonstrated that body weight loss, anxiety-like and cognitive impairments of D-gal-treated animals were reversed by CaD administration as evaluated by the measurement of mice performance in elevated plus-maze, Y-maze, and shuttle box tests. CaD treatment also inhibited the oxidative stress in aging mouse brains by decreasing malondialdehyde (MDA) levels and increasing superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT) enzyme activities. These results could open new perspectives for the clinical use of CaD in treating and preventing cognitive impairment in older people.
Highlights
Senescence is the gradual deterioration of cells or organs during aging [1]
We explored the possible role of Calcium dobesilate (CaD) against anxiety and cognitive dysfunction as well as against oxidative brain damage induced by D-gal treatment in mice
D-gal administration decreased the body weight of treated mice compared to the control untreated group (RMA; F (15, 90) = 8.339; p < 0.001) (Figure 1)
Summary
Senescence is the gradual deterioration of cells or organs during aging [1]. Oxidative stress has been associated with anxiety and cognitive disorders in older people [3]. Several animal models have been proposed to investigate the mechanisms of aging. The “naturally aging model” (the study of the experimental animals over time) may be the most informative to investigate the complexity of aging, it is costly and timeconsuming [5]. The need to reduce the analyses’ time and costs led researchers to develop “accelerating aging models”. Long-term treatment with D-gal in mice reproduces natural oxidative stress in aging through overproduction of ROS, and antioxidant enzyme downregulation [7,8] impacts cognition and behavior [9]
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