Effect of the lipid composition of liposomes on their clearance from the circulation and accumulation in the liver of mice

The effect of phospholipid and ganglioside liposome composition on the liposome clearance from the circulation and accumulation in the mouse liver has been studied. It has been shown that liposomes constituting of liver lipids are quicker removed from the circulation and accumulated in the liver. Liver gangliosides increased liposome uptake by the mouse liver and their clearance from the circulation.     

Ecological and toxicological control over the status of the environment by the methods of physicochemical biology

Xenobiotic metabolism in the fish liver has been investigated with a view of developing test-system for biomonitoring based on multienzyme membrane-bound complexes. Extraction methods of xenobiotics from harmful pollutants and some biological tissue have been described using various sorbents and solvents. The own and literary data on the study of mutagenic effect of this contaminants and carcinogens in the Ames test-system in the presence of postmitochondrial fraction S9 from fish liver with 3-methylcholanthrene induced by microsomal oxidation system have been demonstrated.     

31P-NMR study of the levels of phosphorus-containing metabolites in the mouse liver during administration of highly dispersed zinc powder

The content of phosphor-containing metabolites as regards inorganic phosphate of tissues of the mouse liver after injection of zinc highly dispersed powder at the dose of 5 mg/kg has been established with quantitative calculation of 31P-NMR spectra. A decrease in the relative level of phosphor-containing metabolites in the liver regeneration on the first day after partial hepatectomy has been observed. It has been shown that the relative level of phosphor-containing metabolites after injection more decreased during the first two days after operation. The observed changes of P-compounds metabolites in the liver after injection of zinc highly dispersed powder are related to its stimulation effect on metabolism of sugar and phospholipids and on the cell respiratory process.     

Contribution of the sympathetic hormone epinephrine to the sensitizing effect of ethanol on LPS-induced liver damage in mice

It is well known that ethanol preexposure sensitizes the liver to LPS hepatotoxicity. The mechanisms by which ethanol enhances LPS-induced liver injury are not completely elucidated but are known to involve an enhanced inflammatory response. Ethanol exposure also increases the metabolic rate of the liver, and this effect of ethanol on liver is mediated, at least in part, by the sympathetic hormone, epinephrine. However, whether or not the sympathetic nervous system also contributes to the sensitizing effect of ethanol preexposure on LPS-induced liver damage has not been determined. The purpose of this study was therefore to test the hypotheses that 1) epinephrine preexposure enhances LPS-induced liver damage (comparable to that of ethanol preexposure) and that 2) the sympathetic nervous system contributes to the sensitizing effect of ethanol. Accordingly, male C57BL/6J mice were administered epinephrine for 5 days (2 mg/kg per day) via osmotic pumps or bolus ethanol for 3 days (6 g/kg per day) by gavage. Twenty-four hours later, mice were injected with LPS (10 mg/kg ip). Both epinephrine and ethanol preexposure exacerbated LPS-induced liver damage and inflammation. Concomitant administration of propranolol with ethanol significantly attenuated the sensitizing effect of ethanol on LPS-induced liver damage. These data support the hypothesis that the sympathetic nervous system contributes, at least in part, to the mechanism of the sensitizing effect of ethanol. These results also suggest that sympathetic tone may contribute to the initiation and progression of alcoholic liver disease.     

Inhibition of ethanol-induced liver disease in the intragastric feeding rat model by chlormethiazole

The purpose of this investigation was to assess the effect of chlormethiazole treatment on liver damage in the experimental rat intragastric ethanol-feeding model of alcoholic liver disease. Chlormethiazole has been used in the treatment of alcoholic withdrawal and has been shown to inhibit cytochrome P4502E1. Since treatment of experimental alcoholic liver disease with CYP2E1 inhibitors had an ameliorating effect on liver injury in the rat, chlormethiazole was used to see if it had a similar effect. Rats fed ethanol for 2 months had significantly less liver injury when chlormethiazole was added to the diet, fed intragastrically. The CYP2E1 apoprotein levels, which were increased by ethanol feeding, were also increased when chlormethiazole was fed with ethanol. Chlormethiazole inhibited the increase in the ethanol-induced CYP2E1 activity in vivo, as measured by chlorzoxazone 6-hydroxylation, but did not affect the level of CYP2E1 apoprotein. Likewise, the reduction in proteasome proteolytic enzyme activity produced by ethanol feeding was blunted in chlormethiazole-fed rats. These results support the conclusion that chlormethiazole treatment partially protects the liver from injury by inhibiting CYP2E1 activity in vivo.     

Role of cyclic AMP in the action of dopaminergic D2 receptors of some endocrine glands in rats

Short-term and long-term effects of bromocriptine mesylate (10 mg/kg i.p.) on cyclic AMP contents of the liver and some endocrine glands have been investigated in the presence and absence of sulpiride (10 mg/kg i.p.). Results revealed that bromocriptine caused significant elevations in the cyclic AMP contents of the liver and reduction in its adrenocortical content. Bromocriptine effect on the adrenal cortex was antagonized by sulpiride, whereas its effect on the liver was not changed. Bromocriptine did not change the, cyclic AMP content in the thyroid gland or the ovary.     

Test systems for biomonitoring based on membrane-bound enzyme complexes. IV. Assessment of genotoxic effects in an Ames test system with metabolic activation by the microsomal mono-oxygenases from fish livers

The study of mutagenic effect of 2-aminoantracene and benz(alpha)pyrene on Salmonella triphimurium TA 100 in the Ames test-system in the presence of postmitochondrial fractions S-9 from carp liver with 3-methylcholantrene induced by microsomal oxidation system has been carried out. The metabolic activity and cytochrome P450 contence in carp liver microsomes have been shown to concede considerably those in rats liver. But these characteristics are sufficient for the use of fraction S-9 from carp liver for the study of genotoxic effect of these xenobiotics in the Ames test-system. Several regimes of storage of S-9 preparations from carp liver have been compared. S-9 preparations frozen immediately after isolation preserve their metabolic activity with respect to 2-aminoantracene and benz(alpha)pyrene well.     

Effect of ethanol on the DNA-polymerase activity in the liver subcellular fractions of adult and old rats

The effect of 5% ethanol on DNA polymerase activity in nuclei, mitochondria, microsomes and cytosol of intact and regenerating liver of adult and old rats has been studied. No changes in DNA polymerase activity were detected in subcellular fractions of adult rat liver. On the contrary, the increased activity of intact liver nuclei and decreased activity of regenerating liver microsomes was observed with ageing. These age-dependent peculiarities of DNA polymerase activity in response to 5% ethanol may be related to changes in the enzyme molecules or microenvironment associated with ageing.     

The effect of carnosine on the liver enzyme system in the irradiated body]

The effect of carnosine on post-radioactive changes in lipid peroxidation (LPO) products in blood serum and cytochrome P-450 content in liver microsomes has been studied. Per os administration of carnosine 24 hours prior to irradiation in a minimal lethal dose (7 Gr) markedly decreases the post-radioactive accumulation of LPO products in rat blood serum one hour after irradiation and fully restores the post-radioactive decrease in the cytochrome P-450 content in rat liver microsomes on day 5 after irradiation. Besides, the ability of carnosine to prevent the post-radioactive decline in the activity of UDP-glucuronyl transferase. Another key enzyme of the liver detoxifying system, has been demonstrated. The data obtained testify to the ability of carnosine to provide effective protection against post-radioactive intensification of LPO in irradiated organisms.     

Bioaccumulation of nickel and vanadium in tissues of the catfish Clarias batrachus

Bioaccumulation of nickel and vanadium in the tissues of the liver, kidney, gill, and intestine has been studied following 4 days and 30 days of exposure at sublethal concentrations of nickel and vanadium compounds in the catfish Clarias batrachus. Nickel and vanadium have been found to accumulate in all four tissues observed. High concentrations of nickel and vanadium have been found in the order kidney greater than gill greater than liver greater than intestine during the 4 days and 30 days treatment. A dose-response effect was seen, as the concentration of metals in the tissues increased with concentration and exposure time. The effect on bioaccumulation in the specific tissue provides a better basis for monitoring exposures than whole-body analysis.     

In vivo and in vitro estimations of the direct effect of estrogen on rat hepatocytes tested by the changes in the unusual estrogen-binding protein content

The direct effect of estradiol (E2) on the hepatocytes of mature male rats has been examined by measuring the changes in the unusual estrogen-binding protein (UEBP) content and parallel measuring the level of liver estrogen receptors (ER). The content of UEBP (NUEBP) and ER (NER) in the liver were determined using the quantitative methods for differential specific determination of the E2-binding sites of these proteins. It has been shown that the administration of E2 in vivo induced a considerable decrease in hepatic NUEBP not only in intact males, but also in hypophysectomized males during the initial period after the operation (when the content of hepatic ER was still high) and produced no effect in hypophysectomized males during the later period (when liver ER were depleted). Repeated administration of human growth hormone (hGH) (twice a day) resulted in a considerable increase in NER in hypophysectomized males and restored the sensitivity to the subsequent inhibitory effect of E2 on UEBP. We also used rat hepatocytes after a 4-day primary culturing. These cells had a stable morpho-functional status, high ER level, and sex-differentiated UEBP content. Culturing of mature male rat hepatocytes in the medium containing E2 at concentrations close to physiological levels (10(-10)-10(-7) M) decreased NUEBP in a dose-dependent manner. Hexestrol (10(-7) M) but not cholesterol (10(-5) M) also exhibited a direct effect on NUEBP in cultured rat hepatocytes. The effect of E2 was reversible: statistically significant increase in NUEBP was observed 3 days after 10(-9) M E2 had been removed from the culturing medium. It was concluded that hepatocytes may be a primary target for E2 under physiological conditions and that GH may modulate the direct effect of E2 at the hepatic level by modifying the content of liver ER.     

Effect of ultraviolet rays on peroxidation and its regulation in the rat liver

The indirect effect of rat skin ultraviolet (UV) irradiation on lipid peroxidation and enzymatic systems of the liver has been studied. The processes of lipid peroxidation have been intensified after 72 hours of UV-irradiation, which is evidently due both to the activation of enzymatic system of initiation and propagation of lipid peroxidation and to the parallel decrease of the activity of enzymatic system regulation of given process in liver.     

Enhancement of Aflatoxin B1 induced liver carcinogenesis by portal diversion in the rat

Conflicting results have been reported on the influence of portacaval anastomosis on liver carcinogenesis. The purpose of this investigation was to study the effect of portal diversion on liver carcinogenesis induced in the rat by a potent chemical liver carcinogen, Aflatoxin B1 (AFB1). Liver tumors appeared earlier and were significantly bigger in rats with shunts than in sham-operated controls. Portal diversion also induced in rats fed AFB1 a splenic atrophy with nearly complete disappearance of Malpighian corpuscles suggesting a profound immunodepression. This might be responsible for the enhancement of liver cancer by portacaval anastomosis in the rats fed AFB1. Thus, the influence of portal diversion on liver cancers appears to be multifactorial.     

Effect of endogenous corticosterone on the determination of dexamethasone receptor levels in rat liver cytosol

The effect of endogenous corticosterone on the quantitative measurement of dexamethasone receptors in liver cytosols from developing rats has been studied. Liver cytosols from adrenalectomized rats were preincubated with increasing concentrations of nonlabeled corticosterone and the levels of detectable dexamethasone receptors were subsequently determined either directly or after removal of unbound corticosterone. Corticosterone concentrations of 50 nM or lower had no significant effect on the specific binding of labeled dexamethasone. Higher concentrations of corticosterone resulted in under-estimation of dexamethasone receptor levels. The mean levels of endogenous corticosterone in liver cytosols from 19.5- to 21.5- day fetuses, 22-day fetuses, 6-day-old immature rats and adult rats were 27.40, 11.91, 0.81 and 4.05 nM, respectively. It is concluded that variations in the levels of circulating corticosterone in the rat under normal physiological conditions have no significant effect on the quantitative measurement of total (occupied and unoccupied) receptor sites for dexamethasone in liver cytosol. This is supported by the finding that prior treatment of liver cytosols, from rats at different stages of development, with charcoal to remove unbound steroids has no effect on the amount of detectable dexamethasone receptors.     

Characteristics of the effect of implantation of the human ApoA1 gene on the condition of hepatocytes in rats of varying age

The results obtained show the essential changes in functional state of hepatocyte's plasmatic membrane due to the implantation of human ApoA1 gene to the rat liver. The changes in phospholipid composition, hyperpolarization, increase in activity of membrane bound enzymes, cytochrome P-450 and biosynthesis of liver total proteins have been found. The essential changes characterizing cell effect were more marked in the adult rats, and membrane effect in the old ones.     

四君子汤对免疫抑制小鼠肝脏细菌易位的影响

目的观察四君子汤对免疫抑制小鼠免疫功能及肝脏细菌易位的影响,探讨神经-内分泌-代谢-微生态-免疫网络之间的关系。方法应用氢化可的松制备小鼠免疫功能抑制模型,造成肝脏细菌易位;观察四君子汤对小鼠吞噬细胞功能的影响和细菌易位的控制,同时设自然恢复组和正常对照组进行比较。结果氢化可的松灌喂3d后,小鼠吞噬细胞的吞噬功能明显下降,肝脏出现大量细菌易位;经四君子汤治疗6h后,小鼠吞噬细胞吞噬功能显著提高。肝脏细菌易位明显减少。结论四君子汤能有效地控制免疫抑制小鼠肝脏细菌易位。     

Effect of water-soluble antioxidants on the permeability of lysosomal membranes and on the structure of the liver in rats with thermal burns

Experiments on rats were made to study the effect of water-soluble antioxidants on the permeability of lysosomal membranes of liver cells and liver structure under burn. Antioxidants were injected intraperitoneally shortly after burn, whereas examination was performed after one day. It has been discovered that one day after burn there takes place an appreciable destabilization of lysosomal membranes with the release of a lysosomal matrix enzyme, cathepsin D to the cytoplasm. Liver structure had undergone substantial changes by that time. After administration of water-soluble antioxidants lysosomal membranes got stabilized while liver structure manifested but insignificant disorders.     

Histometric changes in the liver of inbred rats during prevention of hypokinesis]

An experimental investigation on morphological changes in the liver under prophylaxis of hypokinesia has been performed in genetically uniform material--150 premature rats of August and Wistar lines. The prophylaxis has been carried out at hypokinesia as the background produced by training in the treadban and at the combination of the latter with a pharmacological stimulator. The experiment has been performed for two months. In histological preparations of the liver the number of hepatic lobules, hepatocytes and stellate reticuloendotheliocytes per unit of the tissue area have been determined. Nuclear diameters, width of hepatocytes and sinusoid blood capillaries have been measured. Significant histometric changes in structural components of the liver have been stated after 60 days of hypokinesia with decrease of the organ. Prophylactic measures applied with hypokinesia as the background produce certain positive effect, though it is not the same in different indices and in different strains of animals.     

Effect of vitamin B12 on liver and kidney DNA methylation in guinea pigs in the presence of methionine and ATP

Changes of 5-methylcytosine (m5C) content in DNA of guinea-pigs' liver and kidney under the influence of vitamin B12 in the presence of methionine and ATP have been studied. After B12 injection m5C quantity in liver DNA increases in 1,4 times, in kidney DNA in 1,6 times. The methionine and ATP injection lowers B12 effect on the DNA methylation in liver and kidney.