Biomedical subjects

B Tuchweber

Publications and source records attributed to B Tuchweber.

192 records · Page 11Linked to original sources

PubMedDate not supplied

Resistance of the suckling guinea pig to lithocholic acid-induced cholestasis.

Although immaturity of the liver and synthesis of monohydroxy bile acids have been implicated as pathogenic factors in neonatal cholestasis, there is no direct evidence to show that these bile acids induce cholestasis in the newborn. In the present investigation, we compared the effects of lithocholic acid (LCA) injection on bile flow in suckling (2-week-old) and adult (12-week-old) guinea pigs. Bile flow was not modified by LCA in 2-week-old animals, but it was reduced by 50 to 80% in the adults, the decrease being dose-dependent. In the newborn, the injected LCA was mainly secreted in bile (greater than 90%), while in the adults it was distributed between the liver and bile. The percentage of biliary bile acids (as determined by gas-liquid chromatography) in the two groups was similar before and after LCA injection. Morphologic lesions characteristic of LCA-induced cholestasis were observed only in the adult guinea pigs. This study demonstrates that the newborn guinea pig is less susceptible to cholestasis induced by 90 to 180 mumoles per kg body weight of lithocholate and that, in the neonatal liver, there is no defect in the transport of this bile acid from blood to bile.

Age Factors↗

PubMedDate not supplied

Acetone potentiation of chronic liver injury induced by repetitive administration of carbon tetrachloride.

The ability of ketonic compounds to modify the chronic liver injury (cirrhosis) induced by haloalkanes is unknown. To investigate this problem, male Sprague-Dawley rats were treated p.o. twice weekly for 12 weeks with acetone (25 mmoles per kg in corn oil) or corn oil alone (10 ml per kg). The rats were treated p.o. with corn oil (10 ml per kg) or CCl4 (5 mmoles per kg in corn oil) 18 hr after each pretreatment. Animals were killed after 4, 8, 10 or 12 weeks of treatment. Liver-kidney/body weight ratios were computed; biochemical analyses were performed on plasma (ALT, bilirubin and blood urea nitrogen) and liver (collagen) samples. For the 10-week group, liver injury was assessed by a morphometric analysis. Body weight gain was slower in acetone-treated rats given CCl4; 35% died. Compared to corn oil + CCl4-treated rats, acetone + CCl4-treated animals showed significantly lower liver weight/body weight ratios and higher kidney weight/body weight ratio values at all four times. Significantly higher levels occurred at all four times for bilirubin concentrations, and at 4, 8 and 10 weeks for collagen contents. No significant differences were observed in ALT activities between corn oil- and acetone-treated rats challenged with CCl4. Light microscopy revealed that after 10 weeks of treatment, acetone + CCl4-treated animals showed a fully developed cirrhosis, whereas a much less severe lesion was observed in corn oil + CCl4-treated rats. Evidence of nephrotoxicity was observed in the acetone + CCl4 group as exemplified by significantly elevated blood urea nitrogen values. We conclude that acetone treatment increases the extent of fibrosis and accelerates the appearance of cirrhosis induced by CCl4.

Acetone↗

PubMedDate not supplied

Effect of complete sulfation of bile acids on bile formation in rats.

The effect of sulfation of common bile acids on the formation of bile was investigated in male rats by infusing them with the sulfate esters of cholic, chenodeoxycholic, deoxycholic, lithocholic or dehydrocholic acid in four step-wise, increasing doses. Each dose was infused for 30 min and bile collected every 10 min. Control studies were performed by using either albumin solution (the bile acid carrier) or corresponding nonsulfated bile acids at concentrations similar to those of the sulfated products. The secretion of sulfated bile acids was slower and less than that of nonsulfated bile acids, demonstrating transport maximum kinetics rather than the secretory rate maximum characteristic of nonsulfated bile acids. Sulfation significantly increased bile salt-independent bile flow and the choleretic potency of the bile acids tested. With the exception of deoxycholic acid, which had a slight stimulatory effect, bile acid sulfation generally prevented a rise in bile acid-dependent phospholipid and cholesterol secretion. In fact, it reduced biliary phospholipid and cholesterol secretion associated with the secretion of endogenous bile acids. These data are in agreement with the physicochemical properties of sulfated bile acids. They indicate that sulfation prevents the cholestatic action of nonsulfated bile acids, perhaps by increasing bile flow via a high choleretic potential and/or by stimulating bile acid-independent bile flow. The effect of sulfated bile acids on the secretion of biliary phospholipids may protect the canalicular membrane from the detergent properties of bile acids and may thus block the cholestasis which results from high, nonsulfated bile acid concentrations.

Animals↗

PubMedDate not supplied

Lithocholic acid-induced cholestasis in newborn rats.

Susceptibility to lithocholic acid-induced cholestasis was examined in developing rats aged 14, 21 and 70 days. After bile duct cannulation, bile was collected for 30 min prior to, and 120 min following an i.v. injection of [14C]lithocholic acid (LCA). The liver weight/body weight ratio of newborns was significantly smaller than that of adults (3.13 +/- 0.09 at 14 days vs. 4.76 +/- 0.20 at 70 days). Therefore, when the LCA dosage was calculated per g body weight, the livers of newborns were exposed to larger amounts of LCA. The dosage was then given per liver/body weight ratio for an accurate comparison with adults. Bile flow was reduced by 7-18% in newborns, while a maximum decrease of 90% was recorded in adults by 2 h post injection, the latter drop in bile flow being proportional to LCA retention in the liver. In contrast, LCA retention was minimal in young rats with 91-95% of it being excreted via the bile. The decreased susceptibility of newborns to cholestasis appears to be related to their capacity to excrete LCA.

Aging↗

PubMedDate not supplied

Biliary secretion and actin-cytokeratin filament distribution in rat hepatocytes during phalloidin-induced cholestasis.

The relationship between bile secretion (bile flow, bile acids, phospholipids, and cholesterol) and distribution of actin microfilaments (MFs) and cytokeratin (CK) intermediate filaments (IFs) was examined in hepatocytes of rats injected with a single low dose of phalloidin. This treatment induced a transient cholestasis characterized by a rapid development period (0-90 min postinjection) and a slow recovery period (24 h and 5 days postinjection). No significant changes were observed in bile acid secretion during the 5-day period. The phospholipid output dropped to less than 25% at 90 min and was back to the normal value at 24 h postinjection. In a parallel way, the cholesterol secretion dropped to 30% but came back to only 60% of the control level. Nile Red staining demonstrated a concomitant accumulation of lipids both in the cytoplasm and at the surface membrane. Immunostaining of the actin MFs and CK IFs showed that, in contrast with controls where both cytoskeletal networks were preferentially and uniformly localized at the surface membrane (i.e., sinusoidal, basolateral, and canalicular regions), the toxin treatment led to a major targeting of actin to the pericanalicular region at 24 h and a massive accumulation of well-preserved CK IFs in the cytoplasm at 5 days. Interestingly, this accumulation of CK IFs was not linked to any significant variations in CK isoforms. Together, these data indicate that a selective binding of the toxin to sinusoidal membrane actin at the time of injection triggers a sequence of events that culminate in delayed accumulation of actin MFs at the canalicular pole and of CK IFs in the cytoplasm. Moreover, the reversible perturbation of the bile secretory activity implies a functional adaptation of the hepatocytes that parallels the phalloidin-induced reorganization of both cytoskeleton networks.

Actin Cytoskeleton↗

PubMedDate not supplied

Total parenteral nutrition-associated cholestasis in rats: comparison of different amino acid mixtures.

It has been suggested that the quantity of amino acids perfused is a pathogenetic factor in total parenteral nutrition (TPN)-associated hepatotoxicity. However, the effect of the qualitative pattern of amino acid solutions has not been studied. Rats on parenteral nutrition for 5 days received 10.2 g of dextrose and 3.4 g of amino acids daily. Bile flow (microliter/min/g liver protein) after administration of Vamin was 16.2 +/- 0.8, which was similar to that in controls given chow and dextrose iv, but it was significantly higher (p less than 0.001) than those on Travasol (12.3 +/- 0.8). The decrease in bile flow was not related to the large concentrations of alanine and glycine present in Travasol. However, the addition to Travasol of serine present only in Vamin increased bile flow significantly. Bile acid secretion rate, biliary lipid constituents, calcium, sodium, and glucose showed little change. In contrast, alpha-amino nitrogen was increased (p less than 0.05) in Vamin-perfused animals. Steatosis was noted in only a few animals in the Travasol group, and was not associated with an increase in the triglycerides content of the liver. Glycogen and protein content of the livers did not differ. The data show that the composition of amino acid solutions may be a determinant of TPN-induced cholestasis and suggest that the presence of methyl donor amino acids may have a protective effect.

Amino Acids↗

PubMedDate not supplied

Effect of taurine on total parenteral nutrition-associated cholestasis.

A decrease in the formation/secretion of bile has been well documented in animals on total parenteral nutrition (TPN). Either an excess or an imbalance of amino acids (AA) has been most often implicated. In view of recent work showing that taurine promotes bile flow, bile acid secretion, and protects against hepatotoxic bile acids, the effect of adding taurine (15 mg/dL) to an AA solution was examined in guinea pigs on TPN for 3 days. The TPN-taurine group had a larger bile flow than the group without taurine and had bile acid secretory rates (BASR) similar to those of controls who were on saline by central catheter and had free access to food. Bile composition showed an increase in the secondary bile acid, 7-ketolithocholate and a concomitant decrease in chenodeoxycholate (CDC) in both experimental groups. Taurine led to a reversal of the usual predominance of glycine over taurine conjugated bile acids as well as to increases in HCO3 in cholesterol secretion. In response to a challenge with a large load of CDC, the TPN-taurine animals increased their BASR beyond those observed in the two other groups. These observations suggest that the addition of taurine to TPN solutions could play a role in the prevention of altered biliary function associated with AA solutions.

Amino Acids↗

PubMedDate not supplied