Evaluation of the influence of S-adenosylmethionine on systemic and hepatic effects of prednisolone in dogs.
OBJECTIVE
To evaluate the influence of a 1,4-butanedisulfonate stable salt of S-adenosylmethionine (SAMe) administered orally on clinicopathologic and hepatic effects induced by long-term administration of prednisolone in dogs.


METHODS
12 healthy dogs.


METHODS
Following a pilot study (4 dogs), 2 groups of 4 dogs received prednisolone (2.2 mg/kg) orally once daily (84-day trial). One group received SAMe (20 mg/kg/d divided in 2 doses) for 42 days and then a placebo for 42 days; the other group received treatments in the reverse order. Before and during the trial, numerous variables were monitored, including serum total alkaline phosphatase (ALP) and glucocorticoid-induced ALP (G-ALP) activities, serum haptoglobin concentration, and total and oxidized glutathione (TGSH and GSSG) and thiobarbiturate-reacting substances (TBARS) concentrations in erythrocytes and liver tissue (days 0, 42, and 84). Hepatic specimens also were examined microscopically.


RESULTS
The stable salt of SAMe was biologically available; plasma concentrations of SAMe or prednisolone were not affected by coadministration. Compared with baseline values, serum ALP and G-ALP activities and haptoglobin concentrations increased and erythrocyte GSSG and TBARS concentrations decreased with both treatments. Erythrocyte TGSH concentration decreased with the prednisolone-placebo treatment. Administration of SAMe appeared to conserve erythrocyte TGSH values and did not inhibit hepatocyte glycogen vacuolation but increased hepatic TGSH concentration and improved the hepatic tissue GSSG:TGSH ratio.


CONCLUSIONS
In dogs, administration of 20 mg of SAMe/kg/d may mitigate the apparent pro-oxidant influences of prednisolone but did not block development of classic clinicopathologic or histologic features of vacuolar hepatopathy.
Center
Sharon A
SA
Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA.
Warner
Karen L
KL
McCabe
Jennifer
J
Foureman
Polly
P
Hoffmann
Walter E
WE
Erb
Hollis N
HN
D000284:Administration, Oral; D000469:Alkaline Phosphatase / Q000097:blood; D000818:Animals; D001682:Biological Availability; D018592:Cross-Over Studies; D004285:Dogs; D004311:Double-Blind Method; D004910:Erythrocyte Membrane / Q000378:metabolism; D005260:Female; D005914:Globins / Q000032:analysis; D005938:Glucocorticoids / Q000097:blood / Q000494:pharmacology*; D005978:Glutathione / Q000097:blood; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D010865:Pilot Projects; D011239:Prednisolone / Q000097:blood / Q000494:pharmacology*; D011446:Prospective Studies; D012436:S-Adenosylmethionine / Q000008:administration & dosage* / Q000493:pharmacokinetics; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
D005938:Glucocorticoids; D017392:Thiobarbituric Acid Reactive Substances; C067666:hepatoglobin; D012436:S-Adenosylmethionine; D005914:Globins; D011239:Prednisolone; D000469:Alkaline Phosphatase; D005978:Glutathione