Neuroprotective potential of pyrimidine-4-H1-OHa derivatives in experimental cerebral ischemia

Abstract

To evaluate the effect of ten pyrimidine-4-H1-OH derivatives on the change in the activity of mitochondrial respiratory chain complexes and tricarboxylic acid cycle enzymes in rats under experimental brain ischemia. Cerebral ischemia in rats was modeled by irreversible occlusion of the middle cerebral artery. Two hundred and sixty male Wistar rats were administered studied compounds at a dose of 50 mg/kg (orally) and the reference - L-carnitine at a dose of 200 mg/kg (orally) for 72 hours after ischemia modeling (once a day). The activity of mitochondrial complexes (I, II, IV and V) was evaluated by the respirometric method. The activity of complex III and the enzymes of the tricarboxylic acid cycle (aconitase, citrate synthase, α-ketoglutarate dehydrogenase) was evaluated by spectrophotometric method. The analysis was performed in the mitochondrial fraction of the animal brain. The use of pyrimidine-4-H1-OH derivatives containing a conjugated double bond and substituted phenol in the side chain, equally with the reference, contributed to the restoration of the activity of respiratory complexes and enzymes of the tricarboxylic acid cycle. The use of the remaining test compounds did not have a significant effect on the change in the estimated indicators. It is possible to assume the relevance of further study of pyrimidine-4-H1-OH derivatives as neuroprotective agents of metabolic action.