Molecular mechanisms of the cardiotoxic action of anthracycline antibiotics and statin-induced cytoprotective reactions of cardiomyocytes

   
Tursunova N.V.1 , Klinnikova M.G.1, Babenko O.A.1, Lushnikova E.L.1

1. Institute of Molecular Pathology and Pathomorphology, Federal Research Center of Fundamental and Translational Medicine, Novosibirsk, Russia
Section: Review
DOI: 10.18097/PBMC20206605357      PubMed Id: 33140729
Year: 2020  Volume: 66  Issue: 5  Pages: 357-371
The manifestation of the side cardiotoxic effect of anthracycline antibiotics limits their use in the treatment of malignant processes in some patients. The review analyzes the main causes of the susceptibility of cardiomyocytes to the damaging effect of anthracyclines, primarily associated with an increase in the processes of free radical oxidation. Currently, research is widely carried out to find ways to reduce anthracycline cardiotoxicity, in particular, the use of cardioprotective agents in the complex treatment of tumors. Hydroxymethylglutaryl coenzyme A reductase inhibitors (statins) have been shown to improve the function and metabolism of the cardiovascular system under various pathological impacts, therefore, it is proposed to use them to reduce cardiotoxic complications of chemotherapy. Statins exhibit direct (hypolipidemic) and pleiotropic effects due to the blockade of mevalonic acid synthesis and downward biochemical cascades that determine their cardioprotective properties. The main point of intersection of the pharmacological activity of anthracyclines and statins is the ability of both to regulate the functioning of small GTPase from the Rho family, and their effect in this regard is the opposite. The influence of statins on the modification and membrane dislocation of Rho proteins mediates the indirect antioxidant, anti-inflammatory, endothelioprotective, antiapoptotic effect. The mechanism of statin inhibition of doxorubicin blockade of the DNA-topoisomerase complex, which may be important in preventing cardiotoxic damage during chemotherapy, is discussed. At the same time, it should be noted that the use of statins can be accompanied by adverse side effects: a provocation of increased insulin resistance and glucose tolerance, which often causes them to be canceled in patients with impaired carbohydrate metabolism, so further studies are needed here. The review also analyzes data on the antitumor effect of statins, their ability to sensitize the tumor to treatment with cytostatic drug. It has been shown that the relationship between anthracycline antibiotics and statins is characterized not only by antagonism, but also in some cases by synergism. Despite some adverse effects, statins are one of the most promising cardio- and vasoprotectors for use in anthracycline cardiomyopathy.
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Keywords: anthracyclines, HMG-Co-A-reductase inhibitors, Ras-homologous GTPases, NAD(P)H-oxidase, oxidative stress, apoptosis
Citation:

Tursunova, N. V., Klinnikova, M. G., Babenko, O. A., Lushnikova, E. L. (2020). Molecular mechanisms of the cardiotoxic action of anthracycline antibiotics and statin-induced cytoprotective reactions of cardiomyocytes. Biomeditsinskaya Khimiya, 66(5), 357-371.
This paper is also available as the English translation: 10.1134/S1990750821020116
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