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We studied the effects of melatonin on the status of immune organs and parameters of lipid metabolism in rats with alimentary obesity and parameters of lipid metabolism and immune status in Wistar rats kept on high-fat diet and receiving melatonin solution per os. Melatonin leveled the changes in blood and liver parameters of lipid metabolism, which was paralleled by normalization of cellular composition of immune organs. We conclude that melatonin can be a promising agent for the treatment of lipid metabolism and immune status disorders in alimentary obesity. [ABSTRACT FROM AUTHOR]

We studied the influence of high-fat diet on the development of metabolic syndrome in rats of hypertensive ISIAH strain and normotensive WAG strain. In contrast to ISIAH rats, highfat diet in WAG rats led visceral obesity, glucose tolerance, and dyslipidemia. DNA-binding activity of the peroxisome proliferator-activated receptor α (PPARα) decreased in the liver of WAG rats and increased in ISIAH rats. Blood levels of TNF-α, IL-6, and corticosterone increased more significantly in WAG rats. Corticosterone content in the adrenal glands was more markedly reduced in WAG rats. High-fat diet had no effect on BP in ISIAH and WAG rats. It was concluded that ISIAH rats can be used as a genetic model in studies of the mechanism of resistance to the metabolic syndrome. [ABSTRACT FROM AUTHOR]

We studied effects of zymosan, double-stranded RNA, LPS of E. coli and bacterial CpG DNA, agonists of toll-like receptor TLR2, TLR3, TLR4 and TLR9, respectively, on the formation of macrophage/foam cells 24 h after induction of acute peritonitis. Administration of agonists led to transformation of peritoneal macrophages into foam cells and significant activation of cell biosynthesis and increased the content of triglycerides and cholesterol esters in the absence of LDL and irrespective of the capacity of TLR agonists to stimulate neutrophil infiltration and TNF-α production in the peritoneal cavity. [ABSTRACT FROM AUTHOR]

We studied the effect of bezafibrate on hepatic PPARα activity and immune parameters in hypertensive ISIAH rats in comparison with normotensive WAG rats under conditions of LPS treatment. Bezafibrate increased activity of PPARα in WAG rats, but not in ISIAH rats. As differentiated from WAG rats, bezafibrate produced a potent effect on the content of T cell subpopulations in the thymus and spleen of ISIAH rats. Administration of LPS after injection of bezafibrate caused death of 50% ISIAH animals (but not WAG rats), which was associated with low level of HDL cholesterol and increased triglyceride content. Our results suggest that the hypolipidemic treatment ( e.g., bezafibrate) can increase the severity of complications in patients with infectious and inflammatory diseases in association with low level of HDL. [ABSTRACT FROM AUTHOR]

We studied the influence of abnormal illumination regimen on cell composition of the central and peripheral organs of the immune system in ISIAH rats and control WAG rats. In ISIAH rats, 24-h illumination for 14 days led to more pronounced inhibition of cell proliferation and differentiation in the thymus and more pronounced decrease in splenocyte proliferation and T and B cell counts in the spleen in comparison with WAG rats; however, the level of antigen-presenting cells in the spleen of ISIAH increased. We concluded that ISIAH rats are more sensitive to abnormal illumination regimen than WAG rats. Twenty-four-hour illumination was associated with impairments of central differentiation of T cells and activation of systemic inflammation followed by impairment of differentiation regulation, which can aggravate metabolic dysfunctions in these animals. [ABSTRACT FROM AUTHOR]

The effects of LPS from E. coli on DNA-binding activities of PPARα and PPARγ in the liver and immune system parameters of were studied in hypertensive ISIAH rats and normotensive WAG rats. In ISIAH rats characterized by low basal level of PPARα, PPARγ, and HDL, the response of the peripheral immune system compartment to LPS was more pronounced and was not associated with decrease in DNA-binding activities of PPARα observed in WAG. Proinfl ammatory stimulus did not induce proliferative changes in the thymus of ISIAH rats, which can refl ect impaired relationships between the central and peripheral organs of the immune system. The character of regulatory interactions between PPARα and immune cells can differ in various rat strains and depend on initial PPARα activity, HDL level, specifi c features of immune status, resistance to stress, and hormonal and metabolic background. [ABSTRACT FROM AUTHOR]

We studied the effects of cholesterol, its oxidized derivatives mevalonate, and nuclear receptor agonists LXR, RXR, and FXR on the production of transforming growth factor-β1 (TGF- β1) by macrophages. After recruiting of macrophage monocytes into the focus of inflammation, the production of TGF-β1 increased by 3.5 times in comparison with control macrophages. Cholesterol diet stimulated the production of TGF-β1 by 2.5 times. Cholesterol directly stimulated macrophage production of TGF-β1 in vitro, while addition of mevalonate to the incubation medium effectively reduced this induced production. Agonists of nuclear receptor sharply reduced the production of TGF-β1 in recruited macrophages. Under conditions of inflammation, hypercholesterolemia can be a factor of fibrogenesis due to TGF-β1 induction in macrophages, which depends on the products of mevalonate biochemical chain. [ABSTRACT FROM AUTHOR]

Binding and uptake of complexes of endotoxin and low-density lipoproteins (LPS—LDL) in the arterial wall and mononuclear phagocytes were studied under in vitro conditions. Incubation of aortic explants from Wistar rats with complexes of 125I—LDL and S. minnesota R595 LPS or 125I--LDL was accompanied by a 6-fold increase in binding (0°C) and 2-fold increase in the uptake (37°C) of LDL—LPS complexes as compared to free LDL. Binding and degradation of 125I—LDL—LPS complexes in the culture of peritoneal macrophages were higher compared to the corresponding parameters for free 125I—LDL. Our results suggest that the formation of LDL—LPS complexes is followed by the increased binding and accumulation of LDL in the arterial wall and macrophages. These changes probably induce the cascade of major atherogenic events in the vascular wall. [ABSTRACT FROM AUTHOR]

Abstract  We studied the effect of high-cholesterol diet and factors inhibiting 3-hydroxy-3-methyl-glutaryl coenzyme A reductase on the development of liver fibrosis in C57Bl/6 mice with CCl4-or zymosan-induced hepatitis. Feeding a high-cholesterol diet led to a sharp increase in collagen content in the liver tissue of animals with CCl4-induced or zymosan-induced hepatitis. Atorvastatin and calcitriol produced less pronounced fibrogenic effects. Mevalonate partially prevented the development of cholesterol-induced fibrogenesis. High-cholesterol diet led to accumulation of oxysterols, cholesterol esters, and triglycerides and increased the expression of transforming growth factor-β1 mRNA in liver tissue. Cholesterol-induced potentiation of the fibrogenic response is probably associated with transforming growth factor-β1 induction due to accumulation of lipids and oxysterols in the liver. [ABSTRACT FROM AUTHOR]

Abstract  We studied the effect of agonists of peroxisome proliferator-activated receptors α and γ and retinoid X receptors on the concentration and synthesis of lipids in macrophages of C57Bl/6 mice with inflammation induced by intraperitoneal injection of zymosan. We revealed a significant increase in [1-14C]oleate incorporation into cholesterol esters and triglycerides, increase in the content of free cholesterol, cholesterol esters, and triglycerides, and formation of oil red-stained lipid inclusions in peritoneal macrophages 24 h after administration of zymosan in a dose of 50 mg/kg. Treatment with agonists of retinoid X receptors and peroxisome proliferator-activated receptors α and γ 30 min before and 12 h after zymosan injection decreased the synthesis of triglycerides and cholesterol esters, reduced the content of free cholesterol, cholesterol esters, and triglycerides in macrophages, and prevented the formation of cytoplasmic lipid inclusions in macrophage-derived foam cells during inflammation. [ABSTRACT FROM AUTHOR]

CCl4-induced hepatic fibrosis in mice was accompanied by insufficiency of bone marrow myelo- and erythropoiesis. Polymyxin B completely abolished these changes. This phenomenon can be explained by the development of macrophage endotoxin tolerance during hepatic fibrosis. [ABSTRACT FROM AUTHOR]

25-Hydroxycholesterol stimulates and progesterone inhibits cholesterol esterification in mouse peritoneal macrophages in a dose-dependent manner. Fluorescence assay showed nonlinear changes in lipid viscosity and protein-lipid interactions in macrophage membranes under the effect of various doses of 25-hydroxycholesterol and progesterone, therefore opposite effects of studied steroids on acyl-CoA:cholesterol acyltransferase activity were not necessarily related to these factors. [ABSTRACT FROM AUTHOR]

Peculiarities of SiO2-induced granulomas in the liver and subcutaneous fat were studied in C57B1/6, CBA/Lac, BALB/c, C57BR, and C3H/F mice. Infiltrative and fibrogenic responses were interrelated and strain-specific primarily due to various intensities of myelopoiesis. [ABSTRACT FROM AUTHOR]

Abstract  Changes in electrical charge and clearance rate of LDL after the formation of their complexes with bacterial LPS were studied in experiments on Wistar rats. It was found that binding of S. minnesota R595 LPS with 125I-LDL sharply accelerated clearance of the greater part of LDL complexes, but on the other hand induced the appearance of an LDL-LPS subfraction with slower elimination rate compared to free LDL. Electrophoresis showed that after binding of LPS, LDL acquired a negative charge. These data suggest that the formation of LDL-LPS complexes is accompanied by modification of LDL due to which they acquire atherogenic properties. [ABSTRACT FROM AUTHOR]

Preincubation of macrophages with atorvastatin, cholesterol, 25-, 27-hydroxycholesterol, and 7-ketocholesterol reduced the level of TNF-α to 10, 61, 13, 64.5, and 82%, respectively. Addition of mevalonate to the preincubation medium canceled the effects atorvastatin, cholesterol, and 7-ketocholesterol, but not the effects of 25-and 27-hydroxycholesterols. Atorvastatin increased the level of IL-10 by 41%, while 7-ketocholesterol and 25-hydroxycholesterol inhibited its secretion by 48 and 55%. [ABSTRACT FROM AUTHOR]

Products of cholesterol oxidation, 25-hydroxycholesterol and 7-ketocholesterol, in a dose of 1 μg/ml considerably suppress proliferative response in a primary one-way mixed culture of human lymphocytes and have no effect on spontaneous proliferation. Preliminary 18-h separate culturing of the stimulator and responders with these lipids shows that inhibiting effect of these lipids on cell proliferation is associated with their influence on both stimulator and, to a greater extent, responders. Both lipids in the same dose inhibit accumulation of HLA-DR-positive macrophages in a 4-day culture of peripheral blood adherent cells stimulated with lymphokine-containing supernatant. [ABSTRACT FROM AUTHOR]