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At least 19 recordsLinked to original sources
PubMed1990

[Long-term treatment for non-A, non-B chronic hepatitis--effects on hepatitis C virus (HCV)].

We have treated 16 patients with chronic non-A, non-B hepatitis with short term (7-13 weeks) and long term (1 year) interferon. Sustained effect (normalization) of treatment was noted in all by long term treatment, where 7 of 8 with short term treatment showed flare-ups of transaminase after the therapy. In addition, negative turn of anti-HCV antibody was noted in 2 of 5 patients with long term treatment, whereas such change was noted in none of 6 anti-HCV antibody positive patients treated with short term treatment. These data suggest that long term interferon therapy may change natural course of chronic non-A, non-B hepatitis caused by HCV.

Adult↗
PubMed1987

Low-dose dopamine improves effective hepatic blood flow in murine peritonitis.

Diminished effective hepatic blood flow (EHBF) has been postulated as contributory to hepatocellular dysfunction in sepsis. In addition, dopamine has been demonstrated to increase perfusion to selective viscera. In order to examine the effects of peritonitis upon hepatic perfusion and its response to dopamine infusion, peritonitis was induced in rats via cecal ligation and perforation (CLP). Sixteen to 20 hours following insult, cardiac outputs were determined by thermodilution, and effective hepatic blood flow was determined by low-dose galactose clearance. Studies were performed in peritonitis-induced rats (CLP) and sham-operated controls with and without dopamine infusion for 30 minutes (0.5 microgram/100 g/min). Peritonitis resulted in a significant reduction in effective hepatic blood flow (p less than 0.01) despite a maintained cardiac output. Low-dose dopamine infusion resulted in a significant restoration of effective hepatic blood flow in CLP rats without altering cardiac output or hemodynamic status significantly. Dopamine may be beneficial in the maintenance of effective hepatic perfusion in peritonitis.

Animals↗
PubMed1989

Effective hepatic blood flow during cardiopulmonary bypass.

Hepatic dysfunction following cardiopulmonary bypass (CPB) is a relatively frequent finding, and jaundice occurring after CPB is associated with an increased mortality rate. Post-CPB jaundice may be a consequence of inadequate liver perfusion during CPB. To evaluate the potential impact of CPB on effective hepatic blood flow, 10 patients undergoing CPB for cardiac procedures were studied. Effective hepatic blood flow was measured in each patient during the operative procedure but before institution of CPB and during CPB as well. Effective hepatic blood flow was measured by the galactose clearance technique. Blood lactate and pyruvate levels were also measured before and during CPB. During CPB, effective hepatic blood flow was consistently reduced by an average of 19%. Although for most patients this reduction seems well tolerated, in a minority of patients it may contribute to postoperative hepatic dysfunction.

Cardiopulmonary Bypass↗
PubMed1987

Hepatic effects of acrylamide in rainbow trout.

Acrylamide effects on hepatic mixed function oxidase activity were examined in rainbow trout exposed to waterborne acrylamide monomer (0-50 mg/liter) for 14 days. Acrylamide doses of 25 mg/liter and higher produced reversible dose-related histological lesions in the liver characterized by necrosis around the central vein. A profound selective decrease in ethoxyresorufin-O-deethylase activity was observed in hepatic microsomes from acrylamide-treated trout. However, in vitro preincubation of acrylamide with untreated rainbow trout hepatic microsomes with or without NADPH did not produce a similar decrease in ethoxyresorufin-O-deethylase activity. Structural analysis of a trout biliary metabolite of acrylamide, although not identified, revealed the presence of primary alcohol, carboxylic acid, and amide carbonyl functional groups.

7-Alkoxycoumarin O-Dealkylase↗
PubMed1986

Hepatic effects of phthalate esters and related compounds--in vivo and in vitro correlations.

The hepatic effects of phthalate esters and related compounds on peroxisomal and microsomal enzyme activities were investigated in the intact animal and in primary hepatocyte cultures. In vitro studies with a series of phthalate monoesters demonstrated structure activity differences in the induction of the specific peroxisomal marker KCN-insensitive palmitoyl-CoA oxidation and also of carnitine acetyltransferase. These effects could be reproduced in vivo, and potency differences were also observed between di(2-ethylhexyl) phthalate (DEHP) and its straight-chain isomer, di-n-octyl phthalate. In in vivo studies, DEHP, mono(2-ethylhexyl) phthalate, and clofibrate/clofibric acid produced large increases in liver size and peroxisomal enzyme activities in Sprague-Dawley rats and Chinese hamsters, but had less effect in Syrian hamsters. These effects could be largely reproduced in vitro where good responses were obtained with rat and Chinese hamster hepatocytes, but either little or no effect with Syrian hamster and Dunkin-Hartley guinea pig hepatocytes. Both DEHP and clofibrate appeared to induce similar form(s) of microsomal cytochrome P-450 which exhibited a high specificity towards lauric acid hydroxylation. With a range of hypolipidemic agents, including phthalate monoesters, a good correlation was observed between the induction of peroxisomal and microsomal enzyme activities in rat hepatocyte cultures. These results thus demonstrate a good relationship between the in vivo and in vitro effects of phthalate esters and related compounds and suggest that hepatocyte cultures may be useful for further studies on the hepatic effects of peroxisome proliferators.

Animals↗
PubMed1988

Contribution of toxic oxygen intermediates to complement-induced reductions in effective hepatic blood flow.

This study examines the effects of complement activation and of complement-induced oxygen radical production on the principal determinant of hepatic function, i.e., effective hepatic blood flow (EHBF). Female Sprague-Dawley rats received cobra venom factor, 40 units/kg, in two divided doses at 30-minute intervals. At t = 2 hours, thermodilution cardiac output, mean arterial pressure, heart rate, hematocrit, and EHBF by galactose clearance were determined. Complement activation produced a significant depression in EHBF independent of changes in systemic perfusion. To determine whether oxygen radicals participated in the insult, additional animals were pretreated with superoxide dismutase, 6 mg/kg, plus catalase, 15 mg/kg, immediately before complement activation. Concomitant treatment with the oxygen radical scavengers attenuated the degree of complement-induced hepatic ischemia, again independent of effects on systemic perfusion. This study suggests that the reduction in hepatic blood flow that accompanies animal models of trauma and sepsis may result, in part, from the sequelae of complement activation with oxygen radicals as secondary mediators.

Animals↗
PubMed1985

Bedside micro-method for measuring effective hepatic blood flow, with use of first-order galactose clearance pharmacokinetics.

Data from first-order galactose clearance were used to estimate "effective" hepatic blood flow in normal subjects and in patients with hepatic diseases. Galactose clearance was determined by infusing galactose intravenously at a constant rate and measuring its resulting steady-state concentration in blood. The infusion rate must not exceed the maximum rate of galactose clearance by the liver, the "galactose elimination capacity." With this constraint and within the physiological and pathophysiological limits of hepatic blood flow, a constant infusion at 50 mg/min results in steady-state concentrations ranging from 20 to 200 mg/L. To measure galactose within this range, we modified a YSI Model 23A glucose analyzer and, using an immobilized galactose oxidase (EC 1.1.3.9)/hydrogen peroxide electrode system, accurately measured galactose in water and blood. The galactose metabolic clearance rate was calculated for six normal rats and for a normal and a cirrhotic human subject. The speed of the analysis (40 s), the small sample required (25 microL), and the suitability of fresh whole blood as the sample make the method ideal for measuring hepatic blood flow in small laboratory animals as well as for determining at bedside the effective hepatic blood flow in humans.

Animals↗
PubMed1977

Hepatic effect of two hypolipidemic drugs in rats.

Some hepatic effects of the hypolipidemic agents 3,9-di-3-pyridyl-2,4,8,10-tetraoxaspiro-5,5-undecane (compound A) and 2-(4-dibenzofuranyloxy)-2-methylpropionic acid (compound B) were investigated in male rats. The animals were treated orally with these drugs and a reference compound-clofibrate for 10 weeks, the daily doses being 250, 300 and 300 mg/kg body weight respectively. All three drugs caused hepatomegaly with a normal microscopic appearance in liver cells. In rats given compound A, part of some liver cells could be occupied by numerous membranes of smooth endoplasmic reticulum. The hepatocytes of the rats treated with compound B or clofibrate showed a marked increase in microbody profiles and an elevated hepatic catalase activity in comparison to the control animals. Neither the microbodies nor the catalase activity were affected by compound A. Hypolipidemic effects were demonstrated with all three compounds, the most potent activity being shown by compound B. Treatment with this agent resulted in significantly higher catalse activity than with clofibrate.

Animals↗
PubMed1987

Effective hepatic blood flow and hepatic bioenergy status in murine peritonitis.

To assess the effects of sepsis on effective hepatic blood flow (EHBF) and hepatic tissue bioenergy status 250-350 g rats underwent either sham laparotomy or cecal ligation and perforation (CLP). At 5-, 10-, and 20-hr intervals cardiac output (CO), EHBF, and tissue adenine nucleotide levels were measured. CLP rats showed a hyperdynamic response to sepsis at 20 hr, with CO increased by 25% over sham rats. At all time intervals studied EHBF was decreased and at 20 hr it was maximally decreased by 35%. Hepatic energy charge (HEC) was calculated from tissue adenine nucleotide measurements. HEC was not statistically different in sham and CLP rats at 5 hr and was 11 and 9% reduced from sham levels in CLP rats at 10 and 20 hr, respectively. Thus, EHBF is decreased very early in sepsis; before any changes in hepatic bioenergy status are noted. In this hyperdynamic model of sepsis EHBF is decreased early and decreases progressively with time which may contribute to the significant decrease in HEC that is demonstrated.

Adenine Nucleotides↗
PubMed1985

Influence of dose and sex on the disposition and hepatic effects of cinnamyl anthranilate in the B6C3F1 mouse.

Cinnamyl anthranilate is a synthetic food flavouring and fragrance agent, formerly used at very low levels. There is currently some concern over the potential risk to man from its use, since it has been found to cause liver tumours in mice, following the administration of very large doses. This paper reports studies of its disposition and hepatic effects in B6C3F1 mice in relation to dose. Following a single oral dose of 500 mg cinnamyl anthranilate/kg body weight to B6C3F1 mice peak plasma levels of unchanged compound were reached in 30 min, and were higher in males than in females. Unchanged cinnamyl anthranilate in the urine accounted for 0.3-0.4% of the dose. Anthranilic acid (c. 17%) and hippuric acid (35%; the major metabolite of cinnamyl alcohol) were present in the urine, and recoveries of both were higher in females. Groups of male and female B6C3F1 mice were given 0, 10, 100, 1000, 5000, 15,000 and 30,000 ppm cinnamyl anthranilate in the diet. After 4 days, the diet was removed and urine collected for 24 hr. This contained cinnamyl anthranilate (more in males) hippuric and anthranilic acids (more in females) in concentrations that increased with dose. Other animals were given these diets for 19 days and then killed. Relative liver weight and hepatic microsomal cytochrome P-450 increased with increasing dose above 1000 ppm cinnamyl anthranilate, more markedly in males than in females although the maximum response (roughly twofold) was very similar in the two sexes. SDS-PAGE examination of the microsomes revealed the induction of a cytochrome P-450 isozyme of 53.1 kDa, but the aniline hydroxylase and p-nitroanisole O-demethylase activities of the 9000 g supernatant of liver were not induced. The data are discussed in terms of their significance for the human safety evaluation of cinnamyl anthranilate. It is important to note that liver hypertrophy, microsomal enzyme induction and the excretion of unchanged cinnamyl anthranilate all have the same dose-threshold for their appearance. This suggests that the hepatic effects of cinnamyl anthranilate may be mediated by unhydrolysed cinnamyl anthranilate, which is present only at very high doses due to the saturation of its hydrolysis.

Animals↗
PubMed1987

Hepatic effects of repeated halothane anesthetics in the hypoxic rat model.

The hepatic effects of repeated anesthesia of phenobarbital-induced Fischer 344 rats with 1% halothane/14% oxygen were investigated, after anesthetics were administered at either 1-day or 5-day intervals. Urinary excretion of fluoride, a product of reductive halothane metabolism, was increased in the 24-h period following anesthesia, but was the same after the first, second, and third anesthetics. Rats killed 24 h after a single anesthetic all had centrilobular hepatocellular necrosis. All animals killed 24 h after the second or third anesthetic also had centrilobular necrosis, but, in most animals, this was no more extensive than that following a single anesthetic, regardless of whether the interval between anesthetics was one or five days.

Anesthesia, Inhalation↗
PubMed1989

[Measurement of effective hepatic blood flow using 99mTc-PMT SPECT and single blood sampling].

Effective hepatic blood flow (EHBF) was measured from an uptake constant using single blood sampling and 99mTc-PMT hepatobiliary SPECT data. After intravenous injection of 3 mCi (111 MBq) of 99mTc-PMT, serial 1 min SPECT data were obtained for 7 minutes. A time activity curve (TAC) over the heart, that was normalized with the 5 minutes venous sample concentration (%/dose/ml), was used as a blood clearance curve (B(t]. And a TAC of the whole liver, that was normalized with the injected dose of 99mTc-PMT (%/dose), was used as a hepatogram (L(t]. An uptake constant representing EHBF, was estimated from the Rutland's method L. (t)/B(t) was plotted against integral of otB(t)dt/B(t), and the slope of the least square fitted straight line was determined as the uptake constant. In 16 cases, significant correlation was obtained between the 99mTc-PMT hepatic uptake at 5 minutes and the EHBF estimated from the blood clearance (r = 0.85, p less than 0.001). While there was a much better correlation between the EHBF from uptake constant and the EHBF from blood clearance (r = 0.95, p less than 0.001). In conclusion, this analysis for uptake constant of 99mTc-PMT SPECT data enables us to estimate EHBF with single venous sampling and in relatively short acquisition time. This method is thought to be very valuable in clinical practice.

Humans↗
PubMed1991

[Pharmacological study on anti-hepatitis effect of Cotinus coggygria Scop. Syrup].

This paper shows that the Cotinus coggygria syrup has the effect of protecting the liver from chemical damages, reducing tension of the choledochal sphincter, increasing the bile flow and raising the body immunity. The anti-hepatitis effect may be carried out through decreasing transaminase, normalizing functioning of the gallbladder, reducing icterus and enhancing the immunity of the body.

Animals↗
PubMed1990

Hepatic effects of ketoconazole in the male Swiss Webster mouse: temporal changes in drug metabolic parameters.

There have been conflicting observations regarding the effects of ketoconazole on hepatic metabolism. The objectives of these studies were to determine whether ketoconazole was an enzyme inducer or inhibitor in the mouse and then to establish the time frame of these ketoconazole-induced enzyme changes. Ketoconazole was administered (150 mg/kg p.o. X 4 days) to male Swiss Webster mice. Biochemical observations over a period of 6 days following treatment indicated that ketoconazole had a temporal biphasic effect on the liver. Although liver weight and microsomal protein were elevated, all other parameters monitored were lower at 2 h following ketoconazole treatment. At 24 h after the last dose of ketoconazole, hepatic biochemical parameters (liver wt., % liver wt./body wt., microsomal protein, and cytochrome P-450) were statistically elevated, while enzyme activities (benzphetamine N-demethylation, 6 beta- and 7 alpha-hydroxylation of testosterone, formation of androstenedione and UDP-glucuronyltransferase) were inhibited. At 72 h the ketoconazole-induced changes in the hepatic biochemical parameters were comparable to those observed at 24 h, and enzymatic parameters generally appeared to be induced by ketoconazole, with the exception of benzphetamine N-demethylase and UDP-glucuronyltransferase, which exhibited lower enzyme activities. Ethoxyresorufin O-deethylase, 7 alpha-hydroxylation of testosterone and glutathione S-transferase, on the other hand, were unaltered by ketoconazole treatment. The opposing effects of ketoconazole on benzphetamine N-demethylase and ethylmorphine N-demethylase at 72 h were further examined. Enzyme kinetics studies indicated that ketoconazole did not effect the Michaelis constants (Km) of the two substrates, but the maximum velocity (Vmax) of the reactions was altered.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Biochemical characterization of the hepatic effects in mice and rats of 1,4-bis[2-(3,5-dichloropyridyloxy)]benzene, a hepatic neoplasm promoter.

The biochemical effects on the liver of 1,4-bis[2-(3,5-dichloropyridyloxy)]benzene (TCPOBOP), a phenobarbital-like enzyme inducer, were studied in the mouse and rat. In mice a single dose of TCPOBOP (3 mg/kg, ip) caused marked and long-lasting (at least 7 days) induction of liver cytochrome P-450, 7-ethoxycoumarin-O-deethylase, and epoxide hydrolase. TCPOBOP had much less effect in rats than in mice, even at a higher dose (30 mg/kg) TCPOBOP also induced DNA synthesis in mice and rats but ornithine decarboxylase activity only in mice. In addition, in mice but not in rats, TCPOBOP increased microsomal membrane fluidity, as detected by fluorescence polarization measurements.

7-Alkoxycoumarin O-Dealkylase↗