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



Hakimizadeh E1 ; Zamanian M2, 3 ; Gimenezllort L4 ; Sciorati C5 ; Nikbakhtzadeh M6 ; Kujawska M7 ; Kaeidi A1, 8 ; Hassanshahi J1, 8 ; Fatemi I9
Authors
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Authors Affiliations
  1. 1. Physiology-Pharmacology Research Center, Research Institute of Basic Medical Sciences, Rafsanjan University of Medical Sciences, Rafsanjan, 7717933777, Iran
  2. 2. School of Nahavand Paramedical, Hamadan University of Medical Sciences, Hamadan, 6718773654, Iran
  3. 3. Neurophysiology Research Center, Hamadan University of Medical Sciences, Hamadan, 6718773654, Iran
  4. 4. Institute of Neuroscience & Department of Psychiatry and Forensic Medicine, Universitat Autonoma de Barcelona, Barcelona, E-08193, Spain
  5. 5. Division of Immunology, Transplantation and Infectious Diseases, IRCCS Ospedale San Raffaele Scientific Institute, Milan, 20132, Italy
  6. 6. Department of Physiology, School of Medicine, Tehran University of Medical Sciences, Tehran, 14155-6559, Iran
  7. 7. Department of Toxicology, Poznan University of Medical Sciences, Dojazd 30, Poznan, 60-631, Poland
  8. 8. Department of Physiology and Pharmacology, School of Medicine, Rafsanjan University of Medical Sciences, Rafsanjan, 7717933777, Iran
  9. 9. Research Center of Tropical and Infectious Diseases, Kerman University of Medical Sciences, Kerman, 7616913555, Iran

Source: Antioxidants Published:2021


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. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.