Abstract :
Background: Alzheimer’s disease is the main form of dementia, which affects more than 46 million people every year. In the pathogenesis of Alzheimer’s disease, a significant role played mitochondrial dysfunction, which is a promising pharmacotherapeutic target of neuroprotective therapy. In this regard, this study aimed to evaluate the effect of the 4-hydroxy- 3,5-ditretbutyl cinnamic acid on changes of mitochondrial function in experimental Alzheimer’s disease induced by Aβ injection in rats. Methods: Alzheimer’s disease was modeled on Wistar rats by injecting a fragment of β-amyloid (Aß 1-42) into the CA1 part of the hippocampus. The test-compound (4-hydroxy-3,5-ditretbutyl cinnamic acid, 100 mg/kg, per os) and the reference drugs (resveratrol, 20 mg/kg, per os and EGB671, 100 mg/kg, per os) were administered for 60 days after surgery. The restoration of a memorable trace in animals was evaluated in the Morris water maze test. The concentration of β -amyloid, Tau-protein, and changes in parameters characterizing mitochondrial function (cellular respiration, concentration of mitochondrial ROS, activity of apoptosis reactions (caspase-3 and apoptosis induced factor) were also determined. Results: This study showed that the administration of 4-hydroxy-3,5-ditretbutyl cinnamic acid at a dose of 100 mg/kg (per os) in rats with reproduced Alzheimer’s disease contributed to the normalization of mitochondrial respiratory function. It was expressed in the normalization of aerobic metabolism, increased activity of respiratory complexes and stabilization of mitochondrial membrane potential. Also, when animals were treated with 4-hydroxy-3,5- ditretbutyl cinnamic acid, there was a decrease in the concentration of intracellular calcium (by 39.7% (p 0.05)), the intensity of apoptosis reactions, and an increase of the latent time of the mitochondrial permeability transition pore opening (by 3.8 times (p 0.05)), and decreases H2O2 concentration (by 21.2% (p 0.05)). Conclusion: In the course of this study, it was found that 4-hydroxy-3,5-ditretbutyl cinnamic acid exceeds the value of neuroprotective action in compared to the reference agents – resveratrol (20 mg/kg) and Ginkgo biloba extract (EGB671, 100 mg/kg).
