Ethyl pyruvate prevents from chronic cerebral hypoperfusion via preserving cognitive function and decreasing oxidative stress, caspase 3 activation and IL-1β level

Bratisl Lek Listy. 2018;119(8):469-475. doi: 10.4149/BLL_2018_086.

Abstract

Background: One of the important risk factors for dementia is chronic cerebral hypoperfusion (CCH) especially in patients with cerebrovascular disease.

Objectives: In the present study, using rat model of bilateral common carotid artery occlusion, the possible protective effects of ethyl pyruvate (EP) have been explored in terms of memory impairment, oxidative stress, and levels of caspase-3, Na-K ATPase, and IL- 1β.

Methods: Rats were treated with EP (50 mg/kg, i.p) for 4 weeks. Cognitive function was evaluated by Morris Water Maze (MWM). Both levels of caspase-3 and Na-K ATPase in tissue, IL-1β in plasma were measured by ELISA method. Status of oxidative stress in brain was assessed by the measurements of the tissue malondialdehyde (MDA) and reduced glutathione (GSH) contents. RESULTS: Results showed that CCH caused a striking impairment of spatial working memory, accompanied with increased levels of MDA and IL-1β as well as caspase 3 level. The treatment with EP, however, significantly improved the memory impairment. Moreover, the treatment also provided beneficial effects on the disturbances of caspase 3, IL-1β and MDA.

Conclusion: This study strongly imply that the EP administration can alleviate the memory impairment observed due to CCH. The protection provided by EP may result from inhibition of inflammatory response, apoptotic processes and oxidative stress (Fig. 3, Ref. 58).

Keywords: caspase 3 memory impairment.; chronic cerebral hypoperfusion; ethyl pyruvate; oxidative stress.

MeSH terms

  • Animals
  • Brain / metabolism
  • Brain Ischemia / drug therapy*
  • Brain Ischemia / pathology
  • Caspase 3 / blood
  • Caspase 3 / drug effects
  • Cerebrovascular Circulation / physiology*
  • Cognition / physiology
  • Cognition Disorders / etiology*
  • Glutathione / metabolism
  • Hippocampus / drug effects*
  • Hippocampus / metabolism
  • Interleukin-1beta / blood
  • Interleukin-1beta / drug effects
  • Interleukin-1beta / metabolism
  • Male
  • Malondialdehyde / metabolism
  • Maze Learning / drug effects
  • Maze Learning / physiology
  • Oxidative Stress / drug effects*
  • Oxidative Stress / physiology
  • Pyruvates / chemistry*
  • Pyruvates / therapeutic use
  • Rats
  • Spatial Memory

Substances

  • Interleukin-1beta
  • Pyruvates
  • ethyl pyruvate
  • Malondialdehyde
  • CASP3 protein, human
  • Caspase 3
  • Glutathione