Amino acids suppress apoptosis induced by sodium laurate, an absorption enhancer.
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.
Takayama
Chie
C
Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Okayama University, 1-1-1 Tsushima-naka, Okayama 700-8530, Japan.
Mukaizawa
Fuyuki
F
Fujita
Takuya
T
Ogawara
Ken-ichi
K
Higaki
Kazutaka
K
Kimura
Toshikiro
T
D000596:Amino Acids / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D020169:Caspases / Q000378:metabolism; D003106:Colon / Q000166:cytology / Q000187:drug effects; D045304:Cytochromes c / Q000378:metabolism; D053938:DNA Fragmentation / Q000187:drug effects; D004847:Epithelial Cells / Q000187:drug effects; D005079:Excipients / Q000633:toxicity*; D019254:Genes, bcl-2 / Q000187:drug effects; D005998:Glycine / Q000494:pharmacology; D007408:Intestinal Absorption / Q000187:drug effects; D007850:Lauric Acids / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013654:Taurine / Q000494:pharmacology; D014343:Trypan Blue
D000596:Amino Acids; D005079:Excipients; D007850:Lauric Acids; C030358:lauric acid; D013654:Taurine; D045304:Cytochromes c; D020169:Caspases; D014343:Trypan Blue; D005998:Glycine