Document Detail


Sodium valproate inhibits the movement of secretory vesicles in rat hepatocytes.
MedLine Citation:
PMID:  3124828     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
M E Bellringer; K Rahman; R Coleman
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Biochemical journal     Volume:  249     ISSN:  0264-6021     ISO Abbreviation:  Biochem. J.     Publication Date:  1988 Jan 
Date Detail:
Created Date:  1988-03-23     Completed Date:  1988-03-23     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  2984726R     Medline TA:  Biochem J     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  513-9     Citation Subset:  IM    
Affiliation:
Department of Biochemistry, University of Birmingham, U.K.
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MeSH Terms
Descriptor/Qualifier:
Acid Phosphatase / metabolism
Animals
Bile / drug effects
Biliary Fistula / metabolism
Cytoplasmic Granules / drug effects*
Immunoglobulin A / metabolism
Liver / drug effects*,  metabolism
Male
Octanoic Acids / pharmacology
Perfusion
Phospholipids / metabolism
Rats
Rats, Inbred Strains
Serum Albumin / metabolism
Triglycerides / metabolism
Valproic Acid / pharmacology*
Chemical
Reg. No./Substance:
0/Immunoglobulin A; 0/Octanoic Acids; 0/Phospholipids; 0/Serum Albumin; 0/Triglycerides; 124-07-2/caprylic acid; 99-66-1/Valproic Acid; EC 3.1.3.2/Acid Phosphatase
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