Effects of the Long-Term Administration of Uridine on the Functioning of Rat Liver Mitochondria in Hyperthyroidism

Abstract

The effect of uridine (30 mg/kg for 7 days; intraperitoneally) on the functions of liver mitochondria in rats with experimentally induced hyperthyroidism (HT) (200 µg/100 g for 7 days, intraperitoneally) is studied in this paper. An excess of thyroid hormones (THs) led to an intensification of energy metabolism, the development of oxidative stress, a significant increase in the biogenesis, and changes in the content of proteins responsible for the fusion and fission of mitochondria. The injection of uridine did not change the concentration of THs in the blood of hyperthyroid rats (HRs) but normalized their body weight. The exposure to uridine improved the parameters of oxidative phosphorylation and corrected the activity of some complexes of the electron transport chain (ETC) in the liver mitochondria of HRs. The analysis of ETC complexes showed that the level of CI–CV did not change by the action of uridine in rats with the condition of HT. The application of uridine caused a significant increase in the activity of superoxide dismutase and lowered the rate of hydrogen peroxide production. It was found that uridine affected mitochondrial biogenesis by increasing the expression of the genes Ppargc1a and NRF1 and diminishing the expression of the Parkin gene responsible for mitophagy compared with the control animals. In addition, the mRNA level of the OPA1 gene was restored, which may indicate an improvement in the ETC activity and oxidative phosphorylation in the mitochondria of HR. As a whole, the results obtained demonstrate that uridine has a protective effect against HT-mediated functional disorders in the metabolism of rat liver mitochondria.