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Hepatic Effects (hepatic + effects)

Distribution by Scientific Domains

Medical Sciences	80%

Selected Abstracts

Hepatic Effects of Rosiglitazone in Rats with the Metabolic Syndrome

BASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 2 2010
Zvi Ackerman
In this study, we characterized the hepatic effects of rosiglitazone in fructose-enriched diet rats. Rats were randomly divided into three groups. One group was maintained on standard rat chow diet for 6 weeks, whereas the other two groups were given fructose-enriched diet for 6 weeks. Four weeks after the initiation of fructose-enriched diet, one of the fructose-enriched diet groups was also given rosiglitazone (10 mg/kg/day) for an additional 2 weeks. Rosiglitazone administration to the fructose-enriched diet rats was associated with decreases in the following parameters: blood pressure (,17%), plasma triglycerides (,62%), hepatic total lipids (,19%), hepatic triglycerides (,61%), hepatic malondialdehyde (,88%), glutathione reductase activity (,84%). An increase in adiponectin plasma levels (+329%), hepatic phospholipids (+46%), hepatic ,-tocopherol concentrations (+24%) and hepatic paraoxonase activity (+68%) was observed. Rosiglitazone caused a decrease in hepatic macrovesicular steatosis score but no change in hepatic fibrosis. Administration of rosiglitazone, to rats with the metabolic syndrome has limited hepatic favourable effects: it improves hepatic lipid metabolism, decreases macrovesicular steatosis and improves some of the hepatic oxidative,anti-oxidative milieu but has no effect on hepatic fibrosis. [source]

Hepatic effects of an open lung strategy and cardiac output restoration in an experimental lung injury

ACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 5 2010
M. KREDEL
Background: Ventilation with high positive end-expiratory pressure (PEEP) can lead to liver dysfunction. We hypothesized that an open lung concept (OLC) using high PEEP impairs liver function and integrity dependent on the stabilization of cardiac output. Methods: Juvenile female Pietrain pigs instrumented with flow probes around the common hepatic artery and portal vein, pulmonary and hepatic vein catheters underwent a lavage-induced lung injury. Ventilation was continued with a conventional approach (CON) using pre-defined combinations of PEEP and inspiratory oxygen fraction or with an OLC using PEEP set above the lower inflection point of the lung. Volume replacement with colloids was guided to maintain cardiac output in the CON(V+) and OLC(V+) groups or acceptable blood pressure and heart rate in the OLC(V,) group. Indocyanine green plasma disappearance rate (ICG-PDR), blood gases, liver-specific serum enzymes, bilirubin, hyaluronic acid and lactate were tested. Finally, liver tissue was examined for neutrophil accumulation, TUNEL staining, caspase-3 activity and heat shock protein 70 mRNA expression. Results: Hepatic venous oxygen saturation was reduced to 18 ± 16% in the OLC(V,) group, while portal venous blood flow decreased by 45%. ICG-PDR was not reduced and serum enzymes, bilirubin and lactate were not elevated. Liver cell apoptosis was negligible. Liver sinusoids in the OLC(V+) and OLC(V,) groups showed about two- and fourfold more granulocytes than the CON(V+) group. Heat shock protein 70 tended to be higher in the OLC(V,) group. Conclusions: Open lung ventilation elicited neutrophil infiltration, but no liver dysfunction even without the stabilization of cardiac output. [source]

Differential effects of dihalogenated and trihalogenated acetates in the liver of B6C3F1 mice

JOURNAL OF APPLIED TOXICOLOGY, Issue 2 2001
J. Kato-Weinstein
Abstract Haloacetates are produced in the chlorination of drinking water in the range 10,100 ,g l,1. As bromide concentrations increase, brominated haloacetates such as bromodichloroacetate (BDCA), bromochloroacetate (BCA) and dibromoacetate (DBA) appear at higher concentrations than the chlorinated haloacetates: dichloroacetate (DCA) or trichloroacetate (TCA). Both DCA and TCA differ in their hepatic effects; TCA produces peroxisome proliferation as measured by increases in cyanide-insensitive acyl CoA oxidase activity, whereas DCA increases glycogen concentrations. In order to determine whether the brominated haloacetates DBA, BCA and BDCA resemble DCA or TCA more closely, mice were administered DBA, BCA and BDCA in the drinking water at concentrations of 0.2,3 g l,1. Both BCA and DBA caused liver glycogen accumulation to a similar degree as DCA (12 weeks). The accumulation of glycogen occurred in cells scattered throughout the acinus in a pattern very similar to that observed in control mice. In contrast, TCA and low concentrations of BDCA (0.3 g l,1) reduced liver glycogen content, especially in the central lobular region. The high concentration of BDCA (3 g l,1) produced a pattern of glycogen distribution similar to that in DCA-treated and control mice. This effect with a high concentration of BDCA may be attributable to the metabolism of BDCA to DCA. All dihaloacetates reduced serum insulin levels. Conversely, trihaloacetates had no significant effects on serum insulin levels. Dibromoacetate was the only brominated haloacetate that consistently increased acyl-CoA oxidase activity and rates of cell replication in the liver. These results further distinguish the effects of the dihaloacetates from those of peroxisome proliferators like TCA. Copyright © 2001 John Wiley & Sons, Ltd. [source]

Inhibition of Caspases In Vivo Protects the Rat Liver Against Alcohol-Induced Sensitization to Bacterial Lipopolysaccharide

ALCOHOLISM, Issue 6 2001
Ion V. Deaciuc
Background: The mechanisms of liver sensitization by alcohol to Gram-negative bacterial lipopolysaccharide (LPS) remain elusive. The purpose of this study was two-fold: (1) to test the hypothesis that alcohol-enhanced liver apoptosis may be a sensitizing mechanism for LPS and (2) to further characterize the liver apoptotic response to alcohol. Methods: Rats were fed a high-fat, alcohol-containing liquid diet for 14 weeks, treated with LPS (1.0 mg/kg of body weight, intravenously) or saline, followed by injection of a pan-caspase inhibitor {IDN1965;N -[(1,3-dimethylindole-2-carbonyl)-valinyl]-3-amino-4-oxo-5-fluoropentanoic acid; 10 mg/kg of body weight, intraperitoneally} or vehicle, and killed. The following parameters were assessed: plasma aspartate: 2-oxoglutarate aminotransferase activity (AST); liver histology and terminal deoxyribonucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) response; caspase-3, ,8, and ,9 activity; and mRNA and protein expression for two apoptosis-signaling molecules: Fas receptor and Fas ligand; and three apoptosis adaptors: Bax, Bcl-XL, and Bcl-2. Results: Alcohol-feeding-induced liver steatosis, slightly increased caspases' activity, the number of TUNEL-positive nuclei, and facilitated the LPS necrotic effect without affecting mRNA expression of apoptosis signals and adaptors. LPS induced a significant increase in AST and the number of TUNEL-positive nuclei, both effects being more pronounced in alcohol-treated rats. LPS produced hepatic necrosis only in alcohol-treated rats. LPS effects were associated with up-regulation of mRNA expression for both apoptosis adaptors and signaling molecules. IDN1965 administration 3 hr after LPS injection strongly inhibited caspases' activity, particularly that of caspase-3. IDN1965 also abolished the increase in TUNEL-positive nuclei, reversed the effect of LPS on plasma AST in alcohol-treated rats, and prevented LPS-induced necrosis. Conclusions: (1) Alcohol-enhanced liver apoptosis may not involve regulatory steps at the transcriptional level. LPS-induced liver apoptosis seems to involve transcriptional regulation of several apoptosis adaptors. Therefore, alcohol and LPS may enhance liver apoptosis through different mechanisms. (2) Alcohol-enhanced liver apoptosis precedes and may facilitate the hepatic effects of LPS. LPS superimposed on alcohol further elevates the rate of apoptosis in the liver. This may exceed the phagocytosing capacity of the liver so that all the apoptotic cells are not phagocytosed, but rather die of necrosis. [source]