Effectiveness of arginase inhibitors against experimentally induced stroke

  • Waleed Barakat
  • Ahmad Fahmy
  • Mohamed Askar
  • Sherif El-Kannishy
Original Article

Abstract

Stroke is a lethal disease, but it disables more than it kills. Stroke is the second leading cause of death and the most frequent cause of permanent disability in adults worldwide, with 90% of survivors having residual deficits. The pathophysiology of stroke is complex and involves a strong inflammatory response associated with oxidative stress and activation of several proteolytic enzymes. The current study was designed to investigate the effect of arginase inhibitors (L-citruline and L-ornithine) against ischemic stroke induced in rats by middle cerebral artery occlusion (MCAO). MCAO resulted in alteration in rat behavior, brain infarct, and edema associated with disruption of the blood-brain barrier (BBB). This was mediated through overexpression of arginase I and II, inducible NOS (iNOS), malondialdehyde (MDA), advanced glycation end products (AGEs), TNF-α, and IL-1β and downregulation of endothelial nitric oxide synthase (eNOS). Treatment with L-citruline and L-ornithine and the standard neuroprotective drug cerebrolysin ameliorated all the deleterious effects of stroke. These results indicate the possible use of arginase inhibitors in the treatment of stroke after suitable clinical trials are done.

Keywords

Stroke MCAO L-citruline L-ornithine Arginase 

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Waleed Barakat
    • 1
    • 2
  • Ahmad Fahmy
    • 2
  • Mohamed Askar
    • 2
  • Sherif El-Kannishy
    • 1
    • 3
  1. 1.Department of Pharmacology and Toxicology, Faculty of PharmacyTabuk UniversityTabukKingdom of Saudi Arabia
  2. 2.Department of Pharmacology and Toxicology, Faculty of PharmacyZagazig UniversityZagazigEgypt
  3. 3.Analytical Toxicology - Emergency Hospital, Faculty of MedicineUniversity of MansouraMansouraEgypt

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