Administration of 4-Hydroxy-3,5-Di-Tertbutyl Cinnamic Acid Restores Mitochondrial Function in Rabbits with Cerebral Ischemia

Abstract

Abstract The aim of the study is to evaluate the effect of 4-hydroxy-3,5- di-tertbutyl cinnamic acid on the change in mitochondrial function under conditions of experimental cerebral ischemia in rabbits. The study was performed on 48 male rabbits, which were used for modeling permanent cerebral ischemia by occlusion of the common carotid arteries. The test compound was administered before modeling ischemia for 14 days and after the occurrence of reproducing ischemia, in a similar time interval. After that, neurological deficit and the parameters of mitochondrial respiration, the intensity of anaerobic processes, the latent opening time of the mitochondrial permeability transition pore, the value of the mitochondrial membrane potential and the concentration of caspase – 3 were determined. The administration of 100 mg/kg of 4-hydroxy-3,5-di-tertbutyl cinnamic acid into the animals reduced neurological deficit and restored the mitochondrial membrane potential. Prophylactic administration of 4-hydroxy- 3,5-di-tertbutyl cinnamic acid, contributed to an increase in ATPgenerating ability, the maximum level of respiration and respiratory capacity by 4.1 times (p<0.01), 4.8 times (p<0.01) and 4.3 times (p<0.01), respectively. With therapeutic administration, these indicators increased by 11 times (p<0.01), 12.2 times (p<0.01) and 8.6 times (p<0.01), respectively. Also, both the prophylactic and therapeutic use of 4-hydroxy-3,5-di-tret-butyl cinnamic acid normalized aerobic/anaerobic metabolism, as well as reduced the concentration of caspase-3. Based on the obtained data, significant cerebroprotective properties of 4-hydroxy-3,5- di-tertbutyl cinnamic acid can be assumed. Moreover, the potential mechanism of action of this compound may be mediated by the normalization of mitochondrial function.