The evaluation of 2.3-diazepine influence on tissue respiration of the liver and its exocrine function in rats with a rotenone model of Parkinson’s disease

Abstract

Parkinson's disease (PD) is a progressive neurodegenerative disorder, characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta. The causes of PD are not fully understood; however, increasing evidence implicates disturbed respiratory function of the mitochondria and a lack of energy in cells. Aim. To study the effects of 2.3-diazepine (2.3-DP), a new derivative of benzodiazepine, on liver tissue respiration (LTR) and energy dependent processes of bile and bile acids (BAs) production in a rat model of PD. Methods. PD was induced by intraperitoneal injections of rotenone (ROT). LTR (the intensity of the oxygen uptake) was assessed using the polarograph LP-9 (Czech Republic). Secreted bile was collected during 1 hour of the experiment through the polyethylene catheter inserted into the common bile duct. BAs were separated by the method of thin layer chromatography. Results. ROT diminished the index of liver oxygen consumption by 34 % (p<0.001), reduced bile flow by 33.8 % (p<0.001) and disturbed the conjugation of cholic acid with amino acids taurine and glycine reducing the index of conjugation by 29.2 % (p<0.001). ROT also increased by 25.6 % (p<0.001) the part of acidic pathway in the biosynthesis of BAs. The application of 2.3-DP results in full or partial recovery of LTR, bile flow, concentrations of BAs and their ratio in the bile of rats with PD. Conclusion. 2.3-DP markedly affected function of the liver parenchyma in a rat model of PD. This drug changed the intensity of LTR, bile flow and notably modified bile chemical compositions.

Diazepinone effect on liver tissue respiration and serum lipid content in rats with a rotenone model of Parkinson’s disease

“…Ukrainian scientists have synthesized the compounds of benzodiazepine group, characterized by activity relative to the CNS. Preliminary studies have shown that in rats with the ROT model of PD a new drug, 2,3-diazepine had correcting effects on liver tissue respiration and bile secretory function [15]. Some pesticides, including rotenone (ROT), have been found to inhibit complex I of the electronic transport chain, causing mitochondrial dysfunction and generation of reactive oxygen and nitrogen species that lead to oxidative stress [16].…”