Oxidative stress in rat heart mitochondria under a rotenone model of Parkinson’ disease: a corrective effect of capicor treatment
| Autor: | O. O. Gonchar, O. O. Klymenko, T. I. Drevytska, L. V. Bratus, I. M. Mankovska |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: | |
| Zdroj: | The Ukrainian Biochemical Journal, Vol 93, Iss 5, Pp 21-30 (2021) |
| Druh dokumentu: | article |
| ISSN: | 2409-4943 2413-5003 |
| DOI: | 10.15407/ubj93.05.021 |
| Popis: | Biochemical and genetic mechanisms of oxidative stress (OS) developing in rat heart mitochondria were studied in a rotenone model of Parkinson’s disease (PD), and the effect of Capicor (combination of meldonium dihydrate and gamma-butyrobetain dihydrate) on these mechanisms was evaluated. Experiments were carried out on adult male Wistar rats: I – intact rats (control); II –with rotenone administration subcutaneously at dose 3 mg/kg per day along 2 weeks; III – with rotenone/Capicor administration: after rotenone intoxication, capicor was injected intraperitoneally at dose 50 mg/kg per day along following 2 weeks. As OS biomarkers, lipid peroxidation, protein oxidative modification, H2O2 production, the activity of MnSOD, GPx and glutathione pool indexes were measured. The PD-related genes Parkin (PARK2) and DJ-1 (PARK7) as well as MnSOD and DJ-1 protein expressions were detected. Rotenone intoxication increased the intensity of lipid peroxidation, protein oxidative modification, and H2O2 production. These events were accompanied by decreased in GSH content, GSH/GSSG ratio, and GPx activity. Increased ROS production and impaired antioxidant defenses could result from the established DJ-1 gene and DJ-1 protein deficiency. Capicor administration increased the endogenous antioxidant defense, weakening the lipid peroxidation and oxidative modification of mitochondrial proteins. Capicor treatment led to an increase in GSH content and GSH/GSSG ratio in heart mitochondria that may serve as additional indicators of the OS intensity reducing. Capicor promoted overexpression of DJ-1 and PARK2 genes in the heart that may indicate a rise in mitophagy and a decrease in OS. |
| Databáze: | Directory of Open Access Journals |
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