Lowering of liver acetaldehyde but not ethanol concentrations by pretreatment with taurine in ehtanol-loaded rats

Summary A rise in blood and liver acetaldehyde concentrations following ethanol loading (1.5 g/kg b.wt) was significantly reduced when rats were pretreated orally with taurine (0.5 g/kg), a potent in vitro activator of yeast aldehyde dehydrogenase. This taurine pretreatment produced a 4-fold increase in liver taurine content.     

Liver ferritin synthesis following chronic alcohol administration to rats: Modulation by propylthiouracil

Summary Liver ferritin synthesis was inhibited by 22.3% in rats treated with alcohol (2 g/kg) for 45 days. This inhibition was prevented by simultaneous administration (5 mg/kg) of propylthiouracil during the last 15 days. There was no significant effect on liver ferritin concentration.     

Effect of taurine administration on liver lipids in guinea pig

The oral administration of 0.4% taurine in drinking water for 14 consecutive days showed the following hepatic effects in male guinea pig. The percentage of tauro-conjugated biliary bile acids was increased from 17.2-54.2%; the ratio liver weight/body weight was increased, and fatty change was induced. Liver triglyceride concentration was accordingly increased; diglyceride and phosphatidylcholine concentrations were reduced by the treatment, while phosphatidylethanolamine level was not affected. These changes suggest an adverse effect of taurine administration on phosphatidylcholine hepatic synthesis.     

β-alanine and α-L-alanine inhibit the exploratory activity of spontaneously hypertensive rats

Summary 1% -alanine and -L-alanine, when given for 7 days as the only drinking fluid, inhibited the exploratory activity of adult male spontaneously-hypertensive rats (SHR)_but not that of the normotensive Wistar-Kyoto rats (WKR). -Alanine decreased the taurine level in the liver of both strains and in the platelets of SHR. -Alanine decreased the taurine level in the liver of WKR and in the platelets of SHR.This study was supported by the Sigrid Jusélius Foundation.     

Effect of taurine administration on liver lipids in guinea pig

Summary The oral administration of 0.4% taurine in drinking water for 14 consecutive days showed the following hepatic effects in male guinea pig. The percentage of tauro-conjugated biliary bile acids was increased from 17.2–54.2%; the ratio liver weight/body weight was increased, and fatty change was induced. Liver triglyceride concentration was accordingly increased; diglyceride and phosphatidylcholine concentrations were reduced by the treatment, while phosphatidylethanolamine level was not affected. These changes suggest an adverse effect of taurine administration on phosphatidylcholine hepatic synthesis.     

Effect of in vivo irradiation of the rat on the taurine concentration of the heart

Summary The taurine concentration in the heart of the rat (moles/g of tissue) was not modified during 10 days after an in vivo irradiation of 900 R.     

In vivo effect of sodium valproate on mouse liver

The in vivo effect of sodium valproate (SV) on the activity of uridine diphosphate glucuronosyltransferase (UDP-GT) and hepatotoxicity in the mouse liver was studied. Mice were injected intraperitoneally (IP) with SV at doses varying from 50 to 800 mg/kg per day, for six consecutive days (dose-response group) or at a standard dose of 300 mg/g per day for 2-10 days (time-response group), whereas the controls were injected with normal saline. Valproic acid levels had a positive correlation to the dose (P < 0.001) and duration of drug administration (P = 0.006). A gradual increase in UDP-GT activity was observed in doses of up to approximately 400 mg/kg per day, whereas in higher doses the enzyme activity gradually decreased. The time course of UDP-GT activity at the standard dose of 300 mg/kg per day increased progressively, with a maximum up to the sixth day and then had a gradual reduction. Hepatic necrosis (which was unrelated to the dose or the duration of drug administration) was found in 13% of the SV-treated animals and in none of the controls. We conclude that at an optimal dose (300-400 mg/kg per day) and at a time course of 6 days, SV causes liver UDP-GT induction, whereas in higher doses and longer duration of administration, UDP-GT activity is gradually reduced. SV also causes hepatotoxicity unrelated to dose and time course.     

Cysteine oxidase and cysteine sulfinic acid decarboxylase in developing rat liver

Summary The patterns of development of cysteine oxidase (CO) and cysteine sulfinic acid decarboxylase (CSD) in rat liver are not similar. It was observed that CO is not under sex control as CSD is. The results obtained agree with the idea that, in liver, as well as in brain, CSD is the limiting factor for the regulation of taurine biosynthesis.Acknowledments: The authors thank CEA for financial support for the purchasing of labelled substrates.     

Diurnal rhythm of ethanol metabolism in the rat

Male Sprague-Dawley rats injected with 2.0 g/kg of ethanol and analyzed 1 h later at 8 specific times of the day showed diurnal rhythms for alcohol concentrations in the blood, urine, brain and liver tissues. The circadian fluctuation noted for the concentrations of blood and tissue ethanol might indicate a diurnal variation in the enzymatic metabolism of ethanol.     

Primary liver carcinogenesis induced by the pesticide 2-(4-tert-butylphenoxy0-1-methylethyl 2-chloroethyl sulphite (Aramite)]

Wistar rats were fed, during 56 weeks, a diet containing 5 g/kg of Aramite. At the end of the treatment, all the surviving animals show, on anatomo-pathological examination, malignant proliferation of the hepatic tissue and, in certain cases, of biliary ducts. This compound, proposed in the past as acaricide in agriculture, can thus be considered as a model substance for induction of malignant liver tumors.     

Diurnal rhythm of ethanol metabolism in the rat

Summary Male Sprague-Dawley rats injected with 2.0 g/kg of ethanol and analyzed 1 h later at 8 specific times of the day showed diurnal rhythms for alcohol concentrations in the blood, urine, brain and liver tissues. The circadian fluctuation noted for the concentrations of blood and tissue ethanol might indicate a diurnal variation in the enzymatic metabolism of ethanol.Supported by a grant from the US National Aeronautics and Space Administration.     

Effect of acute and chronic ethanol ingestion on the content of reduced glutathione of various tissues of the rat

Summary The effect of acute ethanol ingestion (5 g/kg) by fasted rats, or chronic treatment in fed animals, revealed a significant decrease in the content of reduced glutathione of the liver and kidney. No changes were observed in reduced glutathione levels of the pancreas, intestines, stomach or spleen in the acute model. In this condition, the time course study of the decrease in reduced glutathione levels showed a progressive effect in the liver and a rapid and constant effect in the kidney.These studies were supported by the Grant M 308-792 from the Servicio de Desarrollo Cientifico, Artistico y de Cooperacion Internacional, Universidad de Chile, and by the Research Associateship Program (L.A.V.) from the Natural Sciences and Engineering Research Council of Canada.     

Effect of dietary cholic acid and cholesterol on liver and kidney cystathionase and cysteine sulfinate decarboxylase activities and taurine concentrations in the rat

Summary Hepatic cystathionase and cysteine sulfinate decarboxylase activities are drastically affected by cholic acid added to the diet without cholesterol. When cholic acid and cholesterol are given together, only cysteine sulfinate decarboxylase activity is changed. Neither kidney enzyme activity nor taurine concentrations in the liver and kidney are noticeably modified, whatever the diet.This research was supported by INSERM (Contract 78.152.3) and by CEA.     

Pathological changes in the liver of mice given 2,3,7,8-tetrachlorodibenzo-p-dioxin.

In C57BL/6 mice a single oral dose of 2,3,7,8-tetrachlorodibenzodioxin (LD50 126 mug/kg) results in loss of body weight and death with an enlarged fatty liver after ca. 21 days. A progressive necrotic centrilobular liver lesion is also seen.     

Hepatic regeneration in the rat after subtotal (90%) hepatectomy treated with testosterone

A single dose (120 mg/kg IM) of testosterone administered 1 month before subtotal hepatectomy (90%) in Rats, reduced liver steatosis and allowed complete liver regeneration.     

Effect of latent iron deficiency on the levels of iron, calcium, zinc, copper, manganese, cadmium and lead in liver, kidney and spleen of growing rats

Feeding a marginally low iron content diet (18-20 mg iron/kg diet) to weaned (21-day-old) rats for 8 weeks produced a significant decrease in liver non-heme iron (66%, p less than 0.001) but no change in blood hemoglobin. Total iron contents of liver (56%, p less than 0.01), spleen (20%, p less than 0.05), and kidney (19%, p less than 0.05) were also found to decrease along with increased zinc, copper, calcium, manganese lead and cadmium in various organs. The magnitude of alteration of a metal was different in different organs. However, liver was found to be the most affected organ. Two weeks of rehabilitation with iron-sufficient diet (390 mg iron/kg diet) normalized these altered levels.     

Effect of latent iron deficiency on the levels of iron,calcium, zinc,copper, manganese,cadmium and lead in liver,kidney and spleen of growing rats

Summary Feeding a marginally low iron content diet (18–20 mg iron/kg diet) to weaned (21-day-old) rats for 8 weeks produced a significant decrease in liver non-heme iron (66%, p<0.001) but no change in blood hemoglobin. Total iron contents of liver (56%, p<0.01), spleen (20%, p<0.05), and kidney (19%, p<0.05) were also found to decrease along with increased zinc, copper, calcium, manganese lead and cadmium in various organs. The magnitude of alteration of a metal was different in different organs. However, liver was found to be the most affected organ. Two weeks of rehabilitation with iron-sufficient diet (390 mg iron/kg diet) normalized these altered levels.     

Dietary vitamin E does not protect from endotoxin-induced hepatic microvascular dysfunction

Starting from the concept that lipopolysaccharide (LPS)-associated hepatotoxicity involves the action of reactive oxygen species, the present study was conducted to test whether vitamin E, a lipophilic antioxidant, prevents LPS-induced hepatic microvascular dysfunction and liver injury. Fifty-two rats were divided into three groups and fed diets containing 0 (n=16), 75 (n=18) or 8000 mg (n=18) α-tocopherol acetate/kg food for four weeks. At 1 h and 6 h after intravenous LPS-exposure (10 mg/kg E. coli LPS) hepatic microvascular response and liver injury were assessed by the analysis of Kupffer cell phagocytic activity, leukocyte-endothelial cell interaction and nutritive sinusoidal perfusion (intravital fluorescence epi- illumination technique) as well as bile flow, serum liver enzyme activities and tissue histomorphology. In animals fed with 75 mg vitamin E/kg (standard diet), LPS caused hepatic Kupffer cell activation (increased phagocytic activity) and hepatic microvascular leukocyte activation, with stasis in sinusoids and adherence in postsinusoidal venules (1 h) followed by leukocytic infiltration into tissue (6 h) and progredient sinusoidal perfusion failure (6 h). Hepatic microvascular injury was accompanied by reduced bile flow and enhanced liver enzyme release. Vitamin E-enriched diet (8000 mg/kg) and even vitamin E-deficient diet did not significantly affect LPS-induced hepatic microvascular cell activation and perfusion failure. Thus, we conclude, that vitamin E is not effective to protect from endotoxin-induced hepatic microvascular dysfunction. Received 7 November 1996; received after revision 30 December 1996; accepted 20 January 1997     

Copper metabolism in the LEC rat: Involvement of induction of metallothionein and disposition of zinc and iron

The Cu concentration was about 40 times higher in the liver of LEC (Long-Evans with a cinnamon-like coat color) rats aged 77 days (227.5±21.6 g/g liver) than in Fischer rats (5.2±0.1 g/g liver). However, in the kidney and brain of the LEC rats, Cu concentrations were lower than in these organs of the Fischer rats. Cu concentration in the hepatic metallothionein fraction was about 130 times higher in the LEC rats than in the Fischer rats. The LEC rats showed markedly low concentrations of Cu in the serum and bile. It seems likely that excretion of Cu from the liver into the bile and blood (as ceruloplasmin) is inherently lacking in the LEC rat.     

Liver steatogenic power of high doses of rifampicin in rats]

The possible induction of fatty liver by Rifampicin has been investigated by oral administration of two different doses (200 and 400 mg/kg/24 h) of this antibiotic for a period of 8 days to male and female Rats. The results obtained are more constant and more coherent in male than in female. It is the 400 mg/kg/24 h dose which is more effective, leading to an increase of lipids, triglycerides and cholesterol in the liver and a decrease of serum triglycerides. A dose-effect relationship may exist. These preliminary data lead us to believe that Rifampicin may inhibit the synthesis of the protein moiety of lipoproteins, such as alpha-Amanitin, which is also a RNA-polymerase inhibitor.