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Correction of Mitochondrial Dysfunction by 4-Hydroxy-3,5-Ditretbutyl Cinnamic Acid in Experimental Alzheimer’s Disease Induced by Aβ Injection in Rats
- Source :
- Pharmaceutical Sciences, Vol 27, Iss 3, Pp 313-325 (2021)
- Publication Year :
- 2020
- Publisher :
- Maad Rayan Publishing Company, 2020.
-
Abstract
- Background: Alzheimer’s disease is the main form of dementia, which affects more than46 million people every year. In the pathogenesis of Alzheimer’s disease, a significant roleplayed mitochondrial dysfunction, which is a promising pharmacotherapeutic target ofneuroprotective 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’sdisease 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-ditretbutylcinnamic acid, 100 mg/kg, per os) and the reference drugs (resveratrol, 20 mg/kg, per os andEGB671, 100 mg/kg, per os) were administered for 60 days after surgery. The restoration of amemorable trace in animals was evaluated in the Morris water maze test. The concentrationof 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 acidat a dose of 100 mg/kg (per os) in rats with reproduced Alzheimer’s disease contributed to thenormalization of mitochondrial respiratory function. It was expressed in the normalizationof aerobic metabolism, increased activity of respiratory complexes and stabilization ofmitochondrial 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
- Subjects :
- Mitochondrial ROS
cinnamic acid derivatives
Pharmaceutical Science
Morris water navigation task
Pharmacology
Resveratrol
Neuroprotection
Cinnamic acid
RS1-441
chemistry.chemical_compound
Pharmacy and materia medica
Mitochondrial permeability transition pore
chemistry
Apoptosis
mitochondrial dysfunction
alzheimer's disease
neuroprotection
Respiratory function
General Pharmacology, Toxicology and Pharmaceutics
Subjects
Details
- ISSN :
- 23832886 and 1735403X
- Volume :
- 27
- Database :
- OpenAIRE
- Journal :
- Pharmaceutical Sciences
- Accession number :
- edsair.doi.dedup.....fd1553701fecadd67115daa4f0effca5