scholarly journals Sodium valproate inhibits the movement of secretory vesicles in rat hepatocytes

1988 ◽  
Vol 249 (2) ◽  
pp. 513-519 ◽  
Author(s):  
M E Bellringer ◽  
K Rahman ◽  
R Coleman
Keyword(s):  
Serum Albumin ◽  
Sodium Valproate ◽  
Rat Hepatocytes ◽  
Biliary Fistula ◽  
Rat Serum ◽  
Control Series ◽  
Anti Epileptic Drug ◽  
Series Of Experiments ◽  
Branched Chain ◽  
Rat Livers

Sodium valproate (VPA), a simple 8-carbon branched chain fatty acid, is an effective anti-epileptic drug with an occasional serious side effect of liver damage, including the accumulation of triacylglycerols within hepatocytes, and reductions in serum protein concentrations. By investigating the effects of VPA, using biliary fistula rats and isolated perfused rat livers, we have shown that secretion of triacylglycerols and rat serum albumin at the sinusoidal pole of hepatocytes, and of phospholipids, lysosomal contents, and IgA at their biliary pole, are all reduced, to somewhat different extents, by acute VPA administration. In addition, the vesicular transcytosis of exogenous protein (i.e. bovine serum albumin) from the perfusion fluid into bile is also decreased by VPA administration. To determine whether the phenomena were specific to VPA, a control series of experiments was also performed using octanoate (a straight-chain analogue of VPA). With the biliary fistula rats, octanoate did not show inhibition of secretion as compared with the saline controls; with the isolated perfused livers, however, octanoate did show such an inhibition. These phenomena suggest that VPA inhibition of secretion may be a factor in its hepatotoxicity, as the effects are apparent in both the whole animal and the isolated perfused liver, whereas octanoate is not hepatotoxic in the whole animal. Since when octanoate is administered to the isolated liver it causes an inhibition in secretion similar to that caused by VPA, it may be that the large dose of this compound reaching the liver affects a key step in liver metabolism or vesicle transport under these circumstances. Since octanoate does not normally reach the liver in such amounts, as it will normally be metabolized by other tissues, it is not hepatotoxic in the whole animal as is VPA.

scholarly journals Abnormal secretion of proteins into bile from colchicine-treated isolated perfused rat livers

1983 ◽  
Vol 216 (2) ◽  
pp. 409-414 ◽  
Author(s):  
S G Barnwell ◽  
R Coleman
Keyword(s):  
Serum Albumin ◽  
Protein Composition ◽  
Bile Canaliculus ◽  
Perfusion Fluid ◽  
Rat Serum ◽  
Essential Change ◽  
Rat Livers ◽  
Rat Bile ◽  
Rat Serum Albumin ◽  
Microtubular System

The microtubule poison, colchicine, caused an abnormal output of a variety of proteins into rat bile. After 3 h of exposure to the drug, livers were isolated and perfused with media of defined protein composition. There was no essential change in permeability of the hepatobiliary system to proteins (e.g. bovine serum albumin) entering bile from the perfusion fluid. The rat (serum) albumin and fibrinogen that were secreted into bile from colchicine-treated livers were probably derived from the hepatocytes. Disruption of the microtubular system reduces the secretion of proteins at the sinusoidal face of the hepatocyte and results in an accumulation of secretory vesicles in the cytoplasm. It is suggested that under these conditions some of the vesicles discharge their contents into the bile canaliculus.

scholarly journals The Biosynthesis of Rat Serum Albumin

1972 ◽  
Vol 247 (12) ◽  
pp. 3858-3863 ◽  
Author(s):  
Theodore Peters ◽  
James C. Peters
Keyword(s):  
Serum Albumin ◽  
Rat Serum ◽  
Rat Serum Albumin

scholarly journals Effects of Oral L-Carnitine on Liver Functions after Transarterial Chemoembolization in Intermediate-Stage HCC Patients

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Abeer Hassan ◽  
Yasuhiro Tsuda ◽  
Akira Asai ◽  
Keisuke Yokohama ◽  
Ken Nakamura ◽  
...  
Keyword(s):  
Serum Albumin ◽  
Transarterial Chemoembolization ◽  
Intermediate Stage ◽  
Control Group ◽  
Control Groups ◽  
Medical College ◽  
Impaired Liver ◽  
Liver Functions ◽  
Branched Chain ◽  
And Control

Transarterial chemoembolization (TACE) is usually followed by hepatic dysfunction. We evaluated the effects of L-carnitine on post-TACE impaired liver functions.Methods. 53 cirrhotic hepatocellular carcinoma patients at Osaka Medical College were enrolled in this study and assigned into either L-carnitine group receiving 600 mg oral L-carnitine daily or control group. Liver functions were evaluated at pre-TACE and 1, 4, and 12 weeks after TACE.Results. The L-carnitine group maintained Child-Pugh (CP) score at 1 week after TACE and exhibited significant improvement at 4 weeks after TACE (P<0.01). Conversely, the control group reported a significant CP score deterioration at 1 week (P<0.05) and 12 weeks after TACE (P<0.05). L-carnitine suppressed serum albumin deterioration at 1 week after TACE. There were significant differences between L-carnitine and control groups regarding mean serum albumin changes from baseline to 1 week (P<0.05) and 4 weeks after TACE (P<0.05). L-carnitine caused prothrombin time improvement from baseline to 1, 4 (P<0.05), and 12 weeks after TACE. Total bilirubin mean changes from baseline to 1 week after TACE exhibited significant differences between L-carnitine and control groups (P<0.05). The hepatoprotective effects of L-carnitine were enhanced by branched chain amino acids combination.Conclusion. L-carnitine maintained and improved liver functions after TACE.

scholarly journals Bilirubin/Rat Serum Albumin Interaction.

1986 ◽  
Vol 40b ◽  
pp. 55-59 ◽  
Author(s):  
Peder C. Frandsen ◽  
Rolf Brodersen ◽  
Toshiaki Nishida ◽  
Curt R. Enzell ◽  
Synnøve Liaaen-Jensen ◽  
...  
Keyword(s):  
Serum Albumin ◽  
Rat Serum ◽  
Rat Serum Albumin

scholarly journals Upstream region of rat serum albumin gene promoter contributes to promoter activity: presence of functional binding site for hepatocyte nuclear factor-3

1999 ◽  
Vol 338 (2) ◽  
pp. 241-249 ◽  
Author(s):  
Chin-Hui HSIANG ◽  
Norman W. MARTEN ◽  
Daniel S. STRAUS
Keyword(s):  
Serum Albumin ◽  
Hepg2 Cells ◽  
Promoter Activity ◽  
Gene Promoter ◽  
Upstream Region ◽  
Nuclear Factor ◽  
Hepatocyte Nuclear Factor ◽  
Rat Serum ◽  
Albumin Gene ◽  
Rat Serum Albumin

Transcription of the serum albumin gene occurs almost exclusively in the liver and is controlled in part by a strong liver-specific promoter. The upstream region of the serum albumin gene promoter is highly conserved among species and is footprinted in vitro by a number of nuclear proteins. However, the role of the upstream promoter region in regulating transcription and the identity of the transcription factors that bind to this region have not been established. In the present study, deletion analysis of the rat serum albumin promoter in transiently transfected HepG2 cells demonstrated that elimination of the region between -207 and -153 bp caused a two-fold decrease in promoter activity (P< 0.05). Additional analysis of the -207 to -124 bp promoter interval led to the identification of two potential binding sites for hepatocyte nuclear factor-3 (HNF-3) located at -168 to -157 bp (site X) and -145 to -134 bp (site Y). Electrophoretic mobility-shift assays performed with the HNF-3 X and Y sites demonstrated that both sites are capable of binding HNF-3α and HNF-3β. Placement of a single copy of the HNF-3 X site upstream from a minimal promoter increased promoter activity by about four-fold in HepG2 cells, and the reporter construct containing this site could be transactivated if co-transfected with an HNF-3 expression construct. Furthermore, inactivation of the HNF-3 X site by site-directed mutagenesis within the context of the -261 bp albumin promoter construct resulted in a 40% decrease in transcription (P< 0.05). These results indicate that the positive effect of the -207 to -153 bp promoter interval is attributable to the presence of the HNF-3 X site within this interval. Additional results obtained with transfected HepG2 cells suggest that the HNF-3 Y site plays a lesser role in activation of transcription than the X site.

scholarly journals Repurposing the anti-epileptic drug sodium valproate as an adjuvant treatment for diffuse intrinsic pontine glioma

PLoS ONE ◽  
2017 ◽  
Vol 12 (5) ◽  
pp. e0176855 ◽  
Author(s):  
Clare L. Killick-Cole ◽  
William G. B. Singleton ◽  
Alison S. Bienemann ◽  
Daniel J. Asby ◽  
Marcella J. Wyatt ◽  
...  
Keyword(s):  
Sodium Valproate ◽  
Adjuvant Treatment ◽  
Diffuse Intrinsic Pontine Glioma ◽  
Pontine Glioma ◽  
Anti Epileptic Drug

Megalin/gp330 mediates uptake of albumin in renal proximal tubule

1996 ◽  
Vol 271 (4) ◽  
pp. F900-F907 ◽  
Author(s):  
S. Cui ◽  
P. J. Verroust ◽  
S. K. Moestrup ◽  
E. I. Christensen
Keyword(s):  
Bovine Serum Albumin ◽  
Ligand Binding ◽  
Serum Albumin ◽  
Proximal Tubule ◽  
Proximal Tubules ◽  
Rat Serum ◽  
Gold Particles ◽  
Receptor Associated Protein ◽  
Rat Serum Albumin

Serum albumin filtered in renal glomeruli is reabsorbed very efficiently in the proximal tubule by endocytosis. The present study was undertaken to determine whether megalin/gp330 binds and mediates endocytosis of albumin. Rat serum albumin (RSA) labeled with 125I and colloidal gold particles labeled with bovine serum albumin (BSA) were microinfused into rat surface proximal tubules in vivo, and tubular uptake was determined in the presence or absence of different substances known to interfere with ligand binding to megalin. Binding of 125I-BSA and 125I-RSA to purified megalin was also determined directly using Sepharose columns. The results revealed that the tubular uptake of 125I-labeled RSA was significantly inhibited by receptor-associated protein (RAP), which reduced the uptake by > 50% and by cold RSA. The uptake of BSA gold by the proximal tubule was very intensive. BSA gold was found in small and large endocytic vacuoles, dense apical tubules, and in lysosomes. The uptake was reduced by RAP to 17%, by EDTA to 19%, by BSA to 16%, by megalin to 35%, by cytochrome c to 49%, and, together with gentamicin, there was virtually no uptake. Megalin-Sepharose columns bound 125I-labeled BSA as well as 125I-RSA, the binding was inhibited by RAP and EDTA, and analysis of the eluate revealed the bound tracer to be albumin. In conclusion, the present study demonstrates that megalin is a mediator of albumin reabsorption in renal proximal tubules.

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