The effect of cilostazol on hippocampal memory and oxidative stress biomarkers in rat model of diabetes mellitus

Brain Res. 2019 Jul 15:1715:182-187. doi: 10.1016/j.brainres.2019.03.025. Epub 2019 Mar 23.

Abstract

Diabetes is a global public health crisis worldwide, particularly in developing countries. Diabetes is characterized by a consistent elevation in blood glucose level which leads to several complications including cognitive impairment. Hippocampus, a brain structure responsible for memory, is vulnerable to damage caused by hyperglycemia-induced oxidative stress. In this study, we evaluated the effect of cilostazol, a selective phosphodiesterase 3 inhibitor, on hippocampal memory and oxidative stress biomarkers in streptozotocin-induced diabetes model. Cilostazol was administered to rats intraperitoneally at dose 3 mg/kg. Spatial learning and memory were tested using radial arm water maze (RAWM). BDNF protein, TBARS levels and different antioxidant biomarkers were assessed after dissection of the hippocampus. The diabetic rats showed an increase in the number of the errors during RAWM performance. However, treatment with cilostazol could not showed an improvement in animal's learning and memory performance. The results revealed that diabetic rats showed an increase in TBARS levels and a decrease in an antioxidant enzyme activities (superoxide dismutase (SOD) and glutathione peroxidase (GPx)). Moreover, cilostazol was able to normalize diabetes-induced reduction in the hippocampus activity of SOD and GPx. Moreover, administration of cilostazol normalized diabetes-induced increase in TBARS level, without any significant effect on BDNF level or catalase activity. In conclusion, cilostazol showed no improvement in the learning and memory functions which could be due to the lack of significant cognitive impairment induced by streptozotocin administration. However, cilostazol had shown antioxidant activity through normalization of hippocampal oxidative stress biomarkers.

Keywords: Cilostazol; Diabetes; Hippocampus; Maze; Memory.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain-Derived Neurotrophic Factor / metabolism
  • Catalase / metabolism
  • Cilostazol / pharmacology*
  • Diabetes Mellitus, Experimental / metabolism
  • Diabetes Mellitus, Experimental / physiopathology
  • Glutathione / metabolism
  • Glutathione Peroxidase / metabolism
  • Hippocampus / drug effects*
  • Male
  • Maze Learning / drug effects
  • Memory / drug effects
  • Memory Disorders / etiology
  • Oxidative Stress / drug effects*
  • Rats
  • Rats, Wistar
  • Spatial Learning / drug effects
  • Streptozocin / pharmacology
  • Superoxide Dismutase / metabolism

Substances

  • Brain-Derived Neurotrophic Factor
  • Streptozocin
  • Catalase
  • Glutathione Peroxidase
  • Superoxide Dismutase
  • Glutathione
  • Cilostazol