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B Tuchweber

Publications and source records attributed to B Tuchweber.

At least 73 records · Page 4Linked to original sources
PubMed1989

Effect of aging and dietary restriction on bile acid metabolism in rats.

The aim of the present study was to determine whether increased output of phospholipid in bile during aging may be due to alteration of bile acid composition and stimulated hydrophobic bile acid formation. In female Sprague-Dawley rats we examined the influence of aging and life long dietary restriction (60% of the ad libitum intake) on bile flow, total bile acid secretion, bile acid composition and conjugation pattern, as well as phospholipid output. Rats were cannulated at 3.5, 8-12 and 24-27 months of age and bile collected for analysis. With age, there was a significant reduction in bile flow and total bile acid secretion, however, phospholipid output increased. Restriction of dietary intake exerted a beneficial effect on the age-related decline in bile formation. Studies of bile composition indicated that 12 alpha-hydroxylated bile acids (cholic acid and deoxycholic acid) secretion decreased in aged rats compared to 3.5-month-old rats. This was associated with a corresponding increase in secretion of chenodeoxycholic acid and hyodeoxycholic-ursodeoxycholic acid. However, the magnitude of the change in secretion of these bile acids could not account for the increased output of phospholipid in bile.

Aging↗
PubMed1989

Effect of coinfusion of cholic acid and sulfated cholic acid on bile formation in rats.

The effect of combined infusion of sulfated cholic acid and nonsulfated cholic acid on bile formation was investigated. The data show that the secretion of sulfated cholic acid is slower and does not share the same transport mechanism(s) as nonsulfated cholic acid. Sulfated cholic acid significantly increased bile flow and reduced the secretion of biliary phospholipids, cholesterol, and protein associated with the secretion of exogenous nonsulfated cholic acid, only when they were infused in a ratio higher than 2:1 (sulfated:nonsulfated). Thus it is concluded that sulfated bile acids may protect the liver against the toxic effect of high concentration of bile acids. The relevance of these findings to human cholestasis remains to be determined because sulfated bile acids do not predominate in serum during cholestasis.

Animals↗
PubMed1988

Cholesterol synthesis in the pathogenesis of lithocholic acid-induced cholestasis.

Lithocholic acid (LCA)-induced intrahepatic cholestasis is associated with increased de novo synthesis of hepatic cholesterol and augmented cholesterol content of the liver cell plasma membrane fraction enriched in bile canalicular complexes (BCM). To determine whether inhibition of cholesterol synthesis could prevent LCA-induced cholestasis, adult male Wistar rats were treated daily with the hypocholesterolemic agents, clofibrate (250 mg/kg) or mevinolin (25 mg/kg), for one, two or four days. After bile duct cannulation and bile collection for one hr, the animals were injected intravenously with 120 mumoles/kg of LCA or its carrier (albumin). Cholesterol synthesis was measured in liver homogenates, and its contribution to the BCM was estimated. LCA reduced bile flow by 51%, 35% and 25% after clofibrate pretreatment for one, two and four days, respectively, and by 51%, 30% and 42% in mevinolin-pretreated animals after one, two and four days. In control animals, cholesterol synthesis and the contribution of newly synthesized cholesterol in the BCM were increased after LCA injection. However, despite that cholesterol synthesis and the contribution of newly synthesized cholesterol in the BCM were reduced in drug-pretreated rats, LCA injection caused a relative increase in these parameters of a magnitude similar to that observed in controls. Thus, the ability of LCA injection to augment de novo cholesterol synthesis and its transport to the BCM may be an important pathogenetic step in the development of cholestasis.

Animals↗
PubMed1988

Studies of acute nephrotoxic potential of trichloroethylene in Fischer 344 rats.

Group of male Fischer 344 rats, after pretreatment with phenobarbital (80 mg/kg, ip, 3 d), were treated ip in corn oil with 0, 5.5, 11.0, and 22.0 mmol trichloroethylene (TRI) per kg body weight. Urines were collected 24 h after the treatment and the animals were then sacrificed. The nephrotoxicity of TRI was then studied by measuring certain biochemical parameters characteristic of renal injury and its in vivo metabolism by quantitating the TRI principal urinary metabolites. Treatment of rats with TRI up to 11 mmol/kg did not influence any of the measured biochemical parameters of nephrotoxicity. On the other hand, significant increases in the urinary level of N-acetyl-beta-glucose-D-aminidase (NAG) and glucose as well as serum urea nitrogen were observed at 24 h only at the highest dose level (22 mmol/kg) or TRI. Urinary excretions of both trichloroethanol and trichloroacetic acid reached an apparent saturation at the highest dose level of TRI. In inhalation studies, urinary levels of gamma-glutamyltranspeptidase, NAG, glucose, proteins, and serum urea nitrogen were significantly increased at 24 h when rats were exposed to either 1000 or 2000 ppm TRI for 6 h. The capacity of renal cortical slices to accumulate p-aminohippurate was significantly reduced 24 h after the exposure to 22 mmol TRI/kg (ip), or to 1000 or 2000 ppm TRI. These results have demonstrated that TRI exerts its acute nephrotoxic potential at a very high dose level and produces nephrotoxic insult at the proximal tubular and possibly glomerular regions of the rat kidney, whether exposed by inhalation or by an ip route. These data further indicate an involvement of a capacity-limited metabolism in the expression of acute nephrotoxicity due to TRI in Fischer 344 rats.

Administration, Oral↗
PubMed1988

Contribution of the fluid phase endocytosis to bile flow in cholestasis and choleresis in rats.

Using a single iv injection of 1 mg Evans blue dye/100 g body wt in rats, the contribution of the fluid phase endocytosis to bile flow was estimated. In control rats, this pathway contributed 2-4% of the bile flow or 10-20 microliter/hr/100 g body wt. This contribution was not affected by cholestasis induced by taurolithocholic acid or bile duct obstruction or by choleresis induced by dehydrocholic acid. It is concluded that fluid phase endocytosis does not significantly influence bile formation but, rather, may be implicated in the remodeling of liver cell plasma membranes.

Animals↗
PubMed1987

Biliary lipid secretion in the rat during infusion of increasing doses of unconjugated bile acids.

The aim of the present study was to examine the secretion of biliary components in rats during infusion of increasing doses of either deoxycholic acid, chenodeoxycholic acid or cholic acid and to test the hypothesis that biliary phospholipids may regulate the hepatic bile acid secretory capacity. Analysis of bile samples, collected every 10 min throughout the infusion period showed that there was an elevation of bile acid, phospholipid, cholesterol and alkaline-phosphodiesterase secretion, with all the bile acids, peaking and then gradually declining. Their secretory rates maximum differed and were inversely related to their detergent strength. However, the secretory rates maximum and total output of phospholipids and cholesterol were similar for all bile acids infused. The per cent contribution of phosphatidylcholine to total bile acid-dependent phospholipid secretion was reduced from 84% (in the pre-infusion period) to 59, 46 and 13% at the end of the cholic acid, chenodeoxycholic acid and deoxycholic acid infusions, respectively. This decrease in the per cent contribution of phosphatidylcholine was associated with an increase in the contribution of both sphingomyelin and phosphatidylethanolamine. The biliary phospholipid fatty acid pattern corroborated these changes in the phospholipid classes. Since sphingomyelin and phosphatidylethanolamine are major phospholipids in bile canalicular and other hepatocellular membranes, the marked increase in their secretion in bile during the infusion of high doses of bile acids may indicate solubilization of membrane phospholipids, resulting in membrane structural changes responsible for the reduced excretory function of the liver.

Animals↗
PubMed1987

Dietary restriction influence bile formation in aging rats.

Food restriction is one of the most effective interventions which increases the survival of rodents and influences a variety of physiologic and pathologic processes. Thus, we examined whether life-long caloric restriction would influence bile formation, one of the important hepatic functions. Female Sprague Dawley rats were subjected soon after weaning to a restricted diet (60% of the diet consumed by the rats fed ad libitum) and bile formation determined at 3.5, 12 and 24 months of age. Rats had their bile ducts cannulated under nembutal anesthesia and bile collected at 10 min. intervals. Bile flow rate decreased 35% between 3.5 and 24 months of age. This decrease was associated with a reduction of the bile acid dependent fraction of bile flow (BADF) up to 12 months of age, thereafter the bile acid independent fraction (BAIF) also decreased. Phospholipid and cholesterol secretion rates increased with age, but did not correlate with bile acid secretion. In rats fed the restricted diet, bile flow was about 20% higher at 3-5 months of age when compared with the ad libitum fed group. This bile flow rate remained constant until 24 months of age. The increased bile flow was attributed to higher BADF and BAIF. The phospholipid and cholesterol secretion followed that of bile acids. It thus appears that dietary restriction exerts a beneficial effect on the age related decline in bile formation.

Aging↗
PubMed1987

Studies on the subchronic nephrotoxic potential of styrene in Sprague-Dawley rats.

The nephrotoxic potential low non-toxic dose of styrene was studied in male Sprague-Dawley rats. Groups of rats received i.p. injections of styrene in corn oil at doses 0, 2.9, and 5.8 mmol/kg once daily, 5 days/week for 6 consecutive weeks. After collection of urine for 0-24 and 24-48 h following the end of the treatment, the rats were sacrificed. A significant increase in the excreted urinary volume was noticed at 5.8 mmol styrene during 0-24 and 24-48 h, relative to control, whereas urinary concentrations of gamma-glutamyl transpeptidase and glucose were significantly elevated during the 24-48-h period. Urinary activity of N-acetyl-beta-D-glucosaminidase was increased at the higher dose of styrene during 0-24 and 24-48 h. The capacity of renal cortical slices to accumulate p-aminohippurate was significantly reduced 48 h after the exposure to any dose of styrene. Electron microscopic examination of renal cortex 48 h after the exposure to a higher dose revealed the presence of enlarged mitochondria having more electron dense matrix. The data suggest that subchronic exposure to a very low non-toxic dose of styrene may have the potential to elicit nephrotoxicity preferentially in the proximal tubular region of the rat kidney.

Animals↗
PubMed1987

Effects of various pretreatments on the acute nephrotoxic potential of styrene in Fischer-344 rats.

The effects of various inducers and inhibitors of hepatic microsomal mixed-function oxidase (MFO) system and diethylmaleate treatment on styrene-induced acute nephrotoxicity in male Fischer-344 rats were studied. Groups of rats were pretreated with either 3-methylcholanthrene (15 mg/kg, i.p., 3 days), or phenobarbital (80 mg/kg, i.p., 3 days), or SKF525-A (50 mg/kg, i.p., 1 h), or piperonyl butoxide (300 mg/kg, i.p., 2 h), or diethylmaleate (400 mg/kg, i.p., 90 min) prior to an i.p. administration of styrene (0, 0.6 and 0.9 g/kg) in corn oil. The uptake of p-aminohippurate (PAH) by renal cortical slices, the morphology of renal cortices, as well as urinary excretion of N-acetyl-beta-D-glucosaminidase (NAG) and gamma-glutamyl transpeptidase (gamma-GT) of control and pretreated rats were examined 24 h after styrene. The inducers and inhibitors of MFO system failed to modify further the acute nephrotoxicity of styrene. On the other hand, diethylmaleate pretreatment not only reduced further the uptake of PAH, but also produced further significant increase in the urinary excretion of NAG and gamma-GT observed at the higher dose of styrene. Similarly, ultrastructural studies showed a moderate increase in the severity of kidney damage induced at the higher dose of styrene due to pretreatment with diethylmaleate. These data suggest that tissue glutathione concentrations and hence, corresponding conjugating activity might be important determinants of styrene nephrotoxicity. The results further indicate that a metabolic activation system not involving certain cytochrome P-450 might be responsible in styrene-induced nephrotoxicity.

Animals↗
PubMed1987

Studies of nephrotoxicity due to mixed exposure to styrene and toluene.

Adult male Sprague-Dawley rats were treated simultaneously with 4 mmol styrene per kg i.p., twice a day at an interval of 4 h, and 10 mmol toluene per kg once a day, 5 days a week for 4 consecutive weeks. After the last day of treatment, the rats were placed in metabolism cages for collection of urines for 24 h and then were sacrificed. Such mixed exposure produced significant increases in the urinary excretion of gamma-glutamyl transpeptidase, glucose and proteins as compared to those with either solvent alone. An increase, but not significant, in the urinary excretion of N-acetyl-beta-D-glucosaminidase was also noticed due to such exposure. Electron microscopic examination of renal cortex 24 h after the mixed exposure showed the appearance of many vacuoles of various sizes surrounded by a single membrane, which were not seen in rats treated with either styrene or toluene alone. Metabolism studies showed only a significant increase in the urinary excretion of hippuric acid due to mixed exposure. These data indicate that under certain conditions, mixed subchronic exposure to styrene and toluene may have the potential to increase further the nephrotoxic response as compared to that of either solvent alone.

Animals↗
PubMed1987

Effect of a low protein diet on bile flow and composition in rats.

The effect of feeding a low protein (LP) diet on bile flow and biliary lipid and protein secretion was studied with young female rats. Animals fed a 8% protein diet (LP) for 4, 8 and 12 wk had a significantly lower bile flow and a lower biliary bile acid and protein secretion rate compared with rats fed a 26% protein (normal) diet (NP). The bile acid-independent fraction of bile flow was significantly increased. The slope of the regression line to zero bile acid was markedly smaller in the LP than in the NP group, indicating lower bile acid-dependent bile flow. Biliary phospholipid and cholesterol secretion rates were significantly higher in the LP than in the NP group, demonstrating an uncoupling between bile acid and lipid secretion at the low rates of bile acid secretion. The percentage increase for these parameters was of similar magnitude (30%). Absolute concentrations of bile acid, phospholipid and cholesterol were significantly higher in LP-fed rats than in NP rats, while relative concentration of bile acid was lower and those of cholesterol and phospholipid were higher. Analysis of biliary bile acids showed that the percent contribution of chenodeoxycholic acid and of deoxycholic acid increased significantly in the LP-fed rats, while that of cholic acid decreased. These data indicate that the lower bile flow in the rats fed LP can be attributed to lower bile salt-dependent flow associated with significantly lower choleretic potency of bile acids secreted.

Animals↗
PubMed1987

Effect of chronic administration of taurolithocholate on bile formation and liver ultrastructure in the rat.

In some cholestatic syndromes, lithocholic acid (LCA) has been identified in serum and bile and might play a role in the pathogenesis of cholestasis. Thus, we examined the effect of chronic LCA administration on hepatobiliary function in rats. The taurine-conjugate of LCA (TLCA) was given to male rats at the dose of 50 mg/kg body weight i.v. twice daily for 18 days. Bile flow, biliary secretion rate of bile acids, phospholipids and cholesterol, measured 15 h after the last injection, were normal with the exception of phospholipid, which was significantly higher when compared to controls. Individual bile acids measured by GLC showed that the contribution of chenodeoxycholic and muricholic acids increased while that of cholic acid decreased. By electron microscopy, bile canalicular structures appeared normal except for a widening of the pericanalicular ectoplasm. Evaluation of hepatobiliary function 1 h after an additional injection of TLCA to rats that received the bile acid for 18 days, resulted in the typical acute cholestatic response. Thus chronic administration of TLCA does not influence the acute cholestatic effect of TLCA.

Animals↗
PubMed1987

Liver cell membrane solubilization may control maximum secretory rate of cholic acid in the rat.

The factors modulating the maximum secretory rate of cholic acid were investigated. Rats were infused intravenously with cholic acid in measured stepwise increasing doses (1, 2, 3, and 4 mumol X min-1 X 100 g body wt-1). Each dose was infused for 30 min and bile samples were collected every 10 min. Bile flow, bile acid, cholesterol, individual biliary phospholipids, and the fatty acid profiles of the biliary phospholipids were determined. Microsomal and bile canalicular membrane-enriched fractions were isolated from cholic acid-treated rats at the end of the experiment. Membranes were analyzed for cholesterol, phospholipid, and phospholipid fatty acid composition. During cholic acid infusion, the secretion rates of bile acid, cholesterol, phospholipid, and bile flow initially increased and then declined. No evidence of liver cell damage was observed by light or electron microscopy. Maximum phospholipid secretion rate (13.5 nmol X min-1 X g-1) occurred before peak bile flow and bile acid secretory rate maximum (4.72 microliter X min-1 X g-1 and 375 nmol X min-1 X g-1). When phospholipid output declined, the proportion of sphingomyelins and phosphatidylethanolamine relative to phosphatidylcholine increased. This was also reflected in the fatty acid composition. Cholic acid infusion caused a decline in microsomal and bile canalicular membrane phospholipid content without affecting their phospholipid composition. Depletion of membrane phospholipid resulted in an increase in the cholesterol:phospholipid ratio, which is suggested to be the underlying mechanism for modulating cholic acid secretion.

Animals↗
PubMed1986

The effect of colchicine on the development of lithocholic acid-induced cholestasis. A study of the role of microtubules in intracellular cholesterol transport.

The pathogenesis of lithocholic acid (LCA-Na)-induced cholestasis involves a rapid accumulation of cholesterol in the bile canalicular membrane. Since microtubules play an important role in the intracellular transport of many materials, including cholesterol, the present study was undertaken to assess the extent to which they participate in the development of LCA-Na-induced cholestasis. Rats were pretreated with either colchicine (0.2 mumol/100 g body wt.) or saline solution 90 min before injection with LCA-Na (12 mumol/100 g body wt.). Colchicine, although not increasing bile flow by itself, significantly reduced the cholestasis caused by LCA-Na (57-32% reduction in bile flow) without affecting its metabolism into less toxic bile acids or its distribution in blood, liver or bile. Bile canalicular membranes isolated from animals treated with a combination of colchicine and LCA-Na contained less cholesterol than those treated with LCA-Na alone. However, membranes obtained from rats treated with colchicine alone contained much less cholesterol than did controls. It was found that the total amount of cholesterol accumulated within the bile canalicular membrane following LCA-Na treatment (LCA-Na + colchicine versus colchicine alone compared with LCA-Na versus controls) was unchanged by colchicine treatment. In view of these findings it is suggested that the total amount of cholesterol present within the bile canalicular membrane determines the extent of LCA-Na-induced cholestasis, LCA-Na probably moves cholesterol to the bile canalicular membrane via a microtubule independent pathway, and microtubules are unlikely to function in the transcellular transport of LCA-Na.

Animals↗
PubMed1986

The role of hepatic ornithine transcarbamylase deficiency in the orotic aciduria of pregnant mice.

Groups of normal and heterozygote sparse-fur (spf) mutant mice were studied at various stages of gestation, to assess the effects of normal pregnancy on orotate excretion, hepatic mitochondrial urea cycle enzymes and any predisposition to the development of fatty liver. Results show a higher total daily excretion of urinary orotate by normal pregnant mice on the 8th and 15th days of gestation, which came to within the usual basal range of excretion of non-pregnant mutant heterozygotes with hereditary ornithine transcarbamylase deficiency. Liver ornithine transcarbamylase and carbamyl phosphate synthetase-I activities were reduced in pregnant mice on the 16th day of gestation (P less than 0.05). No fatty change, bile stasis or glycogen depletion was discernible on optical microscopy in normal or mutant mice. Nonspecific changes were seen on ultrastructural examination. Orotic aciduria seen in pregnant mice may be directly related to a physiological deficiency of liver ornithine transcarbamylase. However, the depletion of both the mitochondrial urea cycle enzymes, seen on the 16th day of pregnancy, may be indicative of a metabolic stress at the mitochondrial level.

Animals↗
PubMed1986

Acute nephrotoxic potential of acrylonitrile in Fischer-344 rats.

In view of its very limited information, we have evaluated the acute nephrotoxic potential of acrylonitrile (ACN) in male Fischer-344 rats. ACN was given i.p. in saline to groups of 6 rats at doses 0, 10, 20, 40, 60 and 80 mg/kg. Urines were collected for 48 h and the animals were sacrificed at 24 and 48 h after the exposure. Significant increased levels of urinary volumes, glucose as well as increased levels of N-acetyl-beta-D-glucosaminidase (NAG), were observed at higher dose levels of ACN at 24 h. Light microscopy showed an increase in size and number of renal lysosomes or dense bodies at 60 mg ACN per kg after 48 h. Ultrastructural studies showed increase of dense bodies and endocytotic vacuoles at the same higher dose of ACN at 48 h. Autophagic vacuole formation as well as dilatation of endoplasmic reticulum membranes was also noted at the higher dose level. Acute inhalation exposure to ACN at 200 ppm for 4 h produced increases in the urinary volumes, proteins, glucose, gamma-GT and NAG 24 h after the exposure. These results demonstrate that ACN could produce acute nephrotoxic insult preferably at the proximal tubular region of the rat kidney.

Acetylglucosaminidase↗
PubMed1985

Toxicity of peptides of Amanita virosa mushrooms in mice.

A study was performed on the hepatic reaction of mice to acute intoxication with virotoxins (alaviroidin, viroisin, deoxoviroisin, viroidin, deoxoviroidin) and phalloidin, cyclic peptides isolated from Amanita virosa mushrooms. Purified fractions were administered intraperitoneally at various dosages to determine the LD50 which ranged from 1.0 to 5.3 mg/kg, with viroidin, phalloidin, and viroisin being the most potent. The virotoxins and phalloidin induced hemorrhagic necrosis of the liver. The development of hepatic lesions was followed by enhanced serum alanine aminotransferase (ALT) activity as well as by light and electron microscopic changes. In additional groups, bile ducts were cannulated and bile was collected for 2 hr after injection of the peptides (1 mg/kg) to determine their cholestatic potential. The earliest changes in hepatocytes were plasma membrane invagination and cytoplasmic vacuole formation. At later time periods, erythrocyte accumulation was evident in vacuoles and in the cytoplasm. The severity of hepatic damage, as judged by morphologic analysis, was correlated with serum ALT activity. Two of the peptides tested (viroisin and phalloidin) decreased bile flow by more than 50% over control values. Mild ultrastructural alterations in the bile canalicular pole of hepatocytes were observed during the development of cholestasis. Since virotoxins, like phalloidin, are bound to actin, it is possible that their affinity to cellular actin may be responsible for their hepatotoxicity.

Agaricales↗