Ukr.Biochem.J. 2021; Volume 93, Issue 5, Sep-Oct, pp. 21-30


Oxidative stress in rat heart mitochondria under a rotenone model of Parkinson’ disease: a corrective effect of capicor treatment

O. O. Gonchar*, O. O. Klymenko, T. I. Drevytska,
L. V. Bratus, I. M. Mankovska

Bogomoletz Institute of Physiology, National Academy of Sciences of Ukraine, Kyiv;

Received: 22 March 2021; Accepted: 22 September 2021

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.

Keywords: , , , , ,


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