Document Detail


Amino acids suppress apoptosis induced by sodium laurate, an absorption enhancer.
MedLine Citation:
PMID:  19630065     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The formulation containing sodium laurate (C12), an absorption enhancer, and several amino acids such as taurine (Tau) and L-glutamine (L-Gln) is a promising preparation that can safely improve the intestinal absorption of poorly absorbable drugs. The safety for intestinal mucosa is achieved because the amino acids prevent C12 from causing mucosal damages via several mechanisms. In the present study, the possible involvement of apoptosis, programmed cell death, in mucosal damages caused by C12 and cytoprotection by amino acids was examined. C12 induced DNA fragmentation, a typical phenomenon of apoptosis, in rat large-intestinal epithelial cells while the addition of amino acids significantly attenuated it. C12 alone significantly increased the release of cytochrome C, an apoptosis-inducing factor, from mitochondria, which could be via the decrease in the level of Bcl-2, an inhibiting factor of cytochrome C release. The enhancement of cytochrome C release by C12 led to the activation of caspase 9, an initiator enzyme, and the subsequent activation of caspase 3, an effector enzyme. On the other hand, Tau or L-Gln significantly suppressed the release of cytochrome C from mitochondria and attenuated the activities of both caspases, which could be attributed to the maintenance of Bcl-2 expression.
Authors:
Chie Takayama; Fuyuki Mukaizawa; Takuya Fujita; Ken-ichi Ogawara; Kazutaka Higaki; Toshikiro Kimura
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Journal of pharmaceutical sciences     Volume:  98     ISSN:  1520-6017     ISO Abbreviation:  J Pharm Sci     Publication Date:  2009 Dec 
Date Detail:
Created Date:  2009-11-02     Completed Date:  2010-02-09     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  2985195R     Medline TA:  J Pharm Sci     Country:  United States    
Other Details:
Languages:  eng     Pagination:  4629-38     Citation Subset:  IM    
Copyright Information:
2009 Wiley-Liss, Inc. and the American Pharmacists Association
Affiliation:
Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Okayama University, 1-1-1 Tsushima-naka, Okayama 700-8530, Japan.
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MeSH Terms
Descriptor/Qualifier:
Amino Acids / pharmacology*
Animals
Apoptosis / drug effects*
Blotting, Western
Caspases / metabolism
Colon / cytology,  drug effects
Cytochromes c / metabolism
DNA Fragmentation / drug effects
Epithelial Cells / drug effects
Excipients / toxicity*
Genes, bcl-2 / drug effects
Glycine / pharmacology
Intestinal Absorption / drug effects
Lauric Acids / antagonists & inhibitors*,  toxicity*
Male
Mitochondria / drug effects,  metabolism
Rats
Rats, Wistar
Taurine / pharmacology
Trypan Blue
Chemical
Reg. No./Substance:
0/Amino Acids; 0/Excipients; 0/Lauric Acids; 107-35-7/Taurine; 143-07-7/lauric acid; 56-40-6/Glycine; 72-57-1/Trypan Blue; 9007-43-6/Cytochromes c; EC 3.4.22.-/Caspases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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