Calcium Dobesilate Reverses Cognitive Deficits and Anxiety-Like Behaviors in the D-Galactose-Induced Aging Mouse Model through Modulation of Oxidative Stress

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.

Chlorogenic acid combined with epigallocatechin-3-gallate mitigates d-galactose-induced gut aging in mice

“…Cognitive degeneration is a major pathology during aging 3 . In agreement with other studies, the current results showed that chronic administration of D-galactose causes deleterious neuronal damage, which was prevented by CGA and EGCG 22,23 .…”

“…3 In agreement with other studies, the current results showed that chronic administration of D-galactose causes deleterious neuronal damage, which was prevented by CGA and EGCG. 22,23 Multiple pathways involved in the regulation of aging, particularly, increased expression of p16 and p21 are crucial markers. 21 Though less obvious than brain degeneration, gut also undergoes critical changes during aging with gut permeability increased.…”

Gemfibrozil, a lipid‐lowering drug, reduces anxiety, enhances memory, and improves brain oxidative stress in d‐galactose‐induced aging mice

“…At translational level, models to mimic the aging scenario are used so that they can serve to assess the anti‐oxidant, anti‐inflammatory, and neuroprotective properties of different compounds. A great body of evidence has shown that chronic administration of d ‐galactose ( d ‐gal) triggers aging processes similar to natural aging in experimental animals [9–11]. It is well established that d ‐gal induces aging via the overproduction of ROS, antioxidant enzyme downregulation and affects cognition and behavior [9, 10, 12, 13].…”

Berberine Rescues D-Ribose-Induced Alzheimer‘s Pathology via Promoting Mitophagy

“…The two-way shuttle (TWS) avoidance task can be used to evaluate the memory of mice [ 23 ]. The trend was similar to that of MWM.…”