Features of Myocardial Remodeling and Changes in the Blood Lipid Spectrum in Experimental Doxorubicin-Induced Cardiomyop
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ial Remodeling and Changes in the Blood Lipid Spectrum in Experimental Doxorubicin-Induced Cardiomyopathy and Atorvastatin Administration M. G. Klinnikova, E. V. Koldysheva, N. V. Tursunova, D. E. Semenov, and E. L. Lushnikova
Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 170, No. 7, pp. 33-39, July, 2020 Original article submitted May 7, 2020 Structural myocardial reorganization and changes in the blood lipid spectrum in rats were studied after administration of a single sublethal dose of doxorubicin (15 mg/kg) alone and in combination with atorvastatin (20 mg/kg/day over 7 days). It was established that doxorubicin induced the development of dyslipidemia in experimental animals (the concentrations of total cholesterol, triglycerides, and VLDL increased by 2.2, 2.0, and 1.96 times, respectively; the atherogenic coefficient increased by 3.4 times by day 7 of the experiment). In animals with experimental anthracycline cardiomyopathy treated with atorvastatin, the concentrations of the main components of the blood lipid spectrum increased less markedly. Atorvastatin alone induces moderate myocardial remodeling in comparison with more pronounced changes in the structural organization of the myocardium in rats treated with doxorubicin alone. Course treatment with atorvastatin under conditions of doxorubicin-induced cardiomyopathy reduced the severity of myocardial remodeling: the decrease in the volume density of cardiomyocytes and the increase in the volume density of the connective tissue were less pronounced in the dynamics of the experiment. Key Words: myocardium; remodeling; doxorubicin; atorvastatin; blood lipid spectrum Anthracycline-induced cardiotoxicity still remains an unsolved problem of antitumor therapy [4,6,7]. Unselective action of cytotoxic drugs necessitates the development of protective and regenerative technologies to reduce the negative effects of such substances and to promote the development of tissue-specific regenerative reactions in organs and tissues not involved in the neoplastic process. Importantly, the protective drugs should not affect the antineoplastic effects of antitumor therapy. Significant cytotoxic effects of anthracycline antibiotics necessitate testing the cytoprotective activity of a large number of substances, including drugs with Institute of Molecular Pathology and Pathomorphology, Federal Research Center of Fundamental and Translational Medicine, Novosibirsk, Russia. Address for correspondence: [email protected]. M. G. Klinnikova
pleiotropic properties. Among these drugs are statins, the pleiotropic effects of which were established in a series of experimental and clinical studies [9,10,12]. The positive effect of combined use of anthracycline antibiotics and statins has been shown in a number of studies, in particular, a decrease in oxidative stress and myocardial damage, improvement in cardiac function under the effect of rosuvastatin [5]. It was shown that atorvastatin can protect cardiomyocytes (CMC) from oxidative stress by activating the PI3K/A
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