4-Hydroxy-3,5-di-tret-butyl cinnamic acid restores the activity of the hippocampal mitochondria in rats under permanent focal cerebral ischemia

Document Type : Original Article

Author

Pyatigorsk Medical and Pharmaceutical Institute (Pyatigorsk, Russia, 357532, av. Kalinina 11)

Abstract

Objective(s): Ischemic stroke is a disease with complex pathogenesis that requires timely and rational pharmacological intervention. One possible treatment for this condition may be to improve mitochondrial function as part of neuroprotective therapy.
Materials and Methods: Cerebral ischemic damage was reproduced by middle cerebral artery permanent occlusion in Wistar male rats. 4-hydroxy-3,5-di-tretbutyl cinnamic acid was injected intraperitoneally in dose range of 25 mg/kg, 50 mg/kg, and 100 mg/kg. The time of administration was 3 days from the ischemia modeling. Further, changes in the rats’ cognitive functions in the Morris water maze test were evaluated, and the state of mitochondrial function in the hippocampal tissue was studied.
Results: The study showed that the use of the studied compound dose-dependently improved mitochondrial function in the rat hippocampus. At doses of 20 mg/kg and 50 mg/kg, administration of the test substance increased citrate synthase activity by 55.1% (P<0.05) and 43.4% (P<0.05), respectively and ATP content by 25.7% (P<0.05) and 23.9% (P<0.05). Also, the intensity of oxidative stress (activity of antioxidant enzymes increase whereas the concentration of TBARS reduces) and apoptosis (calcium content, concentration of apoptosis-inducing factor, and caspase-3 activity decrease; latent time of mitochondrial transition permeability pore opening increase) decreased against the background of administration of the test compound. At a dose of 100 mg/kg, the studied compound showed less effectiveness.
Conclusion: Administration of 25 mg/kg and 50 mg/kg 4-hydroxy-3,5-di-tretbutyl cinnamic acid demonstrated neuroprotection action on hippocampal cells under the conditions of irreversible brain ischemia.

Keywords

References

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Iranian Journal of Basic Medical Sciences
Volume 24, Issue 11
November 2021
Pages 1590-1601

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