Abstract
Anthracycline antitumor antibiotics are widely used for the treatment of malignancies, but this group of drugs is known for their cytotoxic effects, especially cardiotoxicity. It has been proven that the adverse effect of anthracyclines on tissues is based on formation of the reactive oxygen species that enhance development of the oxidative stress. Among the body biomolecules proteins are the most sensitive to peroxidation; they can be the primary markers in determining this pathological process at the cellular level. To identify and prevent the oxidative stress is important for prevention of further tissue apoptosis and necrosis. The aim of the study was to investigate the effect of nicotinic acid and the complex compound of germanium with nicotinic acid (MIGU-1) on oxidative modification of myocardial and hepatic proteins in the experimental chronic intoxication with doxorubicin (CID) in rats. The pattern of modifications in the content of protein peroxidation products (neutral and basic 2,4-dinitrophenylhydrazine) in cardiomyocytes and hepatocytes in rats has been determined; it shows intensification of the oxidative stress in CID. Nicotinic acid in the dose of 10 mg/kg daily did not exhibit the hepatoprotective effect in CID. It has been proven that the use of the new complex compound of germanium with nicotinic acid in the dose of 10 mg/kg daily provide attenuation of protein peroxidation in rats’ cardiomyocytes and hepatocytes in CID. The results obtained allow considering MIGU-1 as a drug with a possible cytoprotective activity, and its further study may be topical and prospective.
Highlights
Adverse reactions to drug products take an important place in the structure of morbidity and mortality
The increase in protein oxidative modification (POM) products in cardiomyocytes and hepatocytes in rats with chronic intoxication with doxorubicin (CID) indicates the activation of free radical processes and development of the oxidative stress
These results suggest that the secondary markers of the oxidative stress, neutral aldehyde products of POM, dominate in the control group [7]
Summary
Adverse reactions to drug products take an important place in the structure of morbidity and mortality. Anticancer chemotherapy causes approximately 30% of all adverse reactions, cardiotoxicity being the most common one among them [6]. The study of protein oxidative modification (POM) is stipulated by the role of proteins in the cell and in the body as a whole. They are more susceptible to free radical oxidation, and their oxidation is the earliest and most stable indicator of the intensity of generation of active oxygen species which can be mediators of the cell damage in cardiovascular diseases [4, 9, 15].
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