Db/db mice (carrying a mutation in the gene encoding leptin receptor) show autophagy suppression. Our aim was to evaluate the effect of autophagy inducer trehalose on liver and heart autophagy in db/db mice and to study inflammation dysregulation and the suitability of chitinases’ expression levels as diabetes markers. Thirty-eight male db/db mice and C57/BL mice (control) were used. The db/db model manifested inflammation symptoms: overexpression of TNF-α in the spleen and underexpression of IL-10 in the liver and spleen (cytokine imbalance). Simultaneously, we revealed decreased expression of chitotriosidase (CHIT1) and acid mammalian chitinase (CHIA) in the liver of db/db mice. CHIA expression in db/db mice is significantly lower only in the spleen. Trehalose treatment significantly reduced blood glucose concentration and glycated hemoglobin. Treatment of db/db mice by trehalose was followed by increased autophagy induction in the heart and liver (increased autolysosomes volume density studied by morphometric electron-microscopic method). Trehalose exerted beneficial cardiac effects possibly via increased lipophagy (uptake of lipid droplets). The autophagy activation by trehalose had several positive effects on the heart and liver of db/db mice; therefore, lipophagy activation seems to be a promising therapy for diabetes.

Changes in the blood lipid spectrum and structural reorganization of the rat myocardium in response to injection of a single sublethal dose of doxorubicin (7 mg/kg) alone and in combination with course administration of betulonic acid amide (100 mg/kg/day for 14 days) were studied. Betulinic acid amide in the specified dose exhibited less pronounced cardiotoxic (necrobiotic impairment of cardiomyocytes) and dyslipidemic (increase of cholesterol and triglyceride levels) effects in comparison with doxorubicin. Combined treatment with betulinic acid amide and doxorubicin led to more pronounced remodeling of the myocardium, which was shown by a significant increase of the connective tissue/cardiomyocyte volume ratio detected by day 14 of the experiment.

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We studied proliferative activity of cardiomyocytes (using proliferation marker Ki-67) and compared it with their total number in the heart under conditions of experimental chronic hypercholesterolemia and its combination with hypothyroidism. It was found that Ki-67-positive cells are primarily located in the subepicardial layer near the heart base in both intact and experimental animals. Replicative cardiomyocyte pool in intact rats constituted 1.67 ± 0.33‰ of the total cardiomyocyte population; after 68-day atherogenic diet with exogenous cholesterol alone, the replicative cardiomyocyte pool decreased by 16 % (to 1.40 ± 0.24‰). Treatment with mercazolil against the background of exogenous cholesterol increased this parameter by 40 % (to 2.33 ± 0.88‰). Changes in replicative activity of cardiomyocytes correlated with their total number in the heart and organ weight. We conclude that replicative cardiomyocyte pool primarily includes non-terminally differentiated cardiomyocytes (small mononuclear cardiomyocytes) and their proliferation maintains the total number of cardiomyocytes in the heart under conditions of cytopathic influences and provides the basis for physiological and reparative regeneration of the myocardium.

The type and intensity of remodeling (structural reorganization) of the myocardium in Wistar rats were studied under conditions of experimental chronic dyslipidemia and verapamil treatment. Long (64 days) atherogenic diet caused dyslipidemia and led to reduction of the heart percent weight. The cytopathic effect of dyslipidemia manifested in more intense lytic injuries of cardiomyocytes, development of diffuse and small focal cardiosclerosis under conditions of manifest circulatory disorders. Remodeling of the myocardium during various periods of the experiment manifested in a higher connective tissue/cardiomyocyte volume ratio (by 74% after 30 days and by 58-62% after 64 days of experiment). Verapamil injection promoted attenuation of lytic changes in cardiomyocytes and in fibroplastic reactions of the stroma, but failed to prevent them completely.

We hypothesized that low molecular weight urinary proteins play a role in male-male chemical communication in the water vole, Arvicola ampibius L. We studied the effect of placing soiled litter from strange males into the cage of another sexually mature male on the intensity of its digging and scattering, urination on the litter, and alteration in the levels of low molecular weight proteins (15-25 kDa) excreted in the urine before and after 4 days of exposure as determined by chip electrophoresis. The intensity of digging and scattering was positively correlated with levels of testosterone in serum of males exposed to strange male odors (r = 0.56; P < 0.01), as well as with the concentration of low molecular weight proteins in the donor's urine (r = 0.52, P < 0.05). At the end of the experiment, the level of low molecular weight protein in excreted urine was elevated in the males exposed to the strange male's litter. These results highlight the importance of quantitative inter-individual variation of low molecular weight urinary proteins in the modulation of the physiology and behavior of conspecifics.

In experiments on rats, atherogenic diet led to hypercholesterolemia, while addition of verapamil to the diet led to the development of hypertriglyceridemia in these animals. Dyslipidemia induced significant changes in the cardiomyocyte ultrastructure (lytic changes in myofibrils and sarcoplasmic matrix and aggravation of autophagocytosis) that were most pronounced after addition of mercazolyl alone to the diet. After 30-day atherogenic diet, we observed a decrease in the relative content of RyR2 mRNA (by 67-73%, p<0.01) and SERCA2a mRNA (by 75-91%, p<0.01) in the myocardium. In 64 days these parameters remained reduced: by 64-72% (p<0.05) and 54-62% (p<0.05), respectively. Verapamil treatment reduced the severity and number of lytic lesions in cardiomyocytes, induced considerable glycogen accumulation in the sarcoplasm and its sequestration, promoted normalization, and prevented pronounced decrease of the relative RyR2 mRNA and SERCA2a mRNA in rat myocardium.

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