Reversal of cyclosporine A-induced alterations in biliary secretion by S-adenosyl-L-methionine in rats.
This study examines the ability of S-adenosyl-L-methionine to prevent or antagonize the cyclosporine A-induced adverse effects on biliary secretion in the rat. S-adenosyl-L-methionine was administered as a single bolus 3, 5 and 8 hr before administering a single dose of cyclosporine A, and also concurrently administered with cyclosporine A for 1 or 2 wk. Acute S-adenosyl-L-methionine preadministration attenuated the cyclosporine-induced cholestasis and inhibition of bile acids, cholesterol and phospholipid biliary secretion. S-adenosyl-L-methionine pretreatment for 1 wk and simultaneous cotreatment with cyclosporine for 1 or 2 wk not only maintained the beneficial effects reported above but further improved them because the adverse effects of the immunosuppressor drug were prevented or antagonized by S-adenosyl-L-methionine. These results provide the first direct evidence of the ability of exogenously administered S-adenosyl-L-methionine to antagonize cyclosporine-induced abnormalities in biliary bile acids, lipids and protein secretion. The beneficial effects of S-adenosyl-L-methionine could be related, at least in part, to the improvement in the hepatobiliary transport of bile acids.
Fernández
E
E
Department of Physiology and Pharmacology, Universidad de Salamanca, Spain.
Galán
A I
AI
Morán
D
D
González-Buitrago
J M
JM
Muñoz
M E
ME
Jiménez
R
R
D000818:Animals; D001647:Bile Acids and Salts / Q000378:metabolism; D001659:Biliary Tract / Q000187:drug effects* / Q000378:metabolism*; D002779:Cholestasis / Q000139:chemically induced / Q000517:prevention & control; D002784:Cholesterol / Q000378:metabolism; D016572:Cyclosporine / Q000037:antagonists & inhibitors* / Q000633:toxicity; D004334:Drug Administration Schedule; D004347:Drug Interactions; D007166:Immunosuppressive Agents / Q000037:antagonists & inhibitors* / Q000633:toxicity; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D010743:Phospholipids / Q000378:metabolism; D011506:Proteins / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012436:S-Adenosylmethionine / Q000494:pharmacology* / Q000627:therapeutic use
D001647:Bile Acids and Salts; D007166:Immunosuppressive Agents; D010743:Phospholipids; D011506:Proteins; D012436:S-Adenosylmethionine; D016572:Cyclosporine; D002784:Cholesterol