Енергетичний обмін у печінці щурів із паркінсонічним синдромом, індукованим ротеноном, при дії метаніндіазенону

Abstract

Parkinson’s disease (PD) is symptomatically characterized by motor disorders in the human body, which are associated with the degeneration of dopamine neurons in the substantia nigra of the midbrain. It is widely recognized that mitochondrial dysfunction occurs in dopaminergic neurons, leading to their death and the development of this pathology. Recently, benzodiazepine derivatives have been found to have a neuroprotective effect against damage of dopaminergic neurons in an experimental model of Рarkinsonian syndrome (PS). The aim of this study was to investigate the effect of a novel molecule, named methanіdiazenone, on energy metabolism in the liver of rats induced by rotenone. To achieve the set goal, the concentration of ATP, ADP, AMP, hypoxanthine аnd xanthine were determined in the bile samples of rats with PS by the method of thin-layer chromatography. The obtained data indicate that under the influence of rotenone compared to the control values the content of ATP in bile decreased by 40%, while the levels of AMP, xanthine and hypoxanthine, on the contrary, increased by 87,5%, 55,6%, and 25%, respectively. Our findings suggested that the ratio of AMP/ATP, which is an important indicator of the functional state of mitochondria, under the influence of rotenone increased by 200% compared to the control. Metanindiazenone in a dose of 1,0 and 2,0 mg/kg normalized all studied parameters of purine metabolism. The presented results show that methanindiazenone significantly improves purine metabolism in the liver of rats with PS induced by rotenone, indicating the normalization of mitochondrial function in hepatocytes. Thus, methanindiazenone may be recommended for clinical trials regarding its use in combination with other drugs to treat Parkinson’s disease and possibly other neurodegenerative diseases, in which mitochondrial dysfunction occurs.