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.
Animals—12 healthy dogs.
Procedure—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 GALP
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 and Clinical Relevance—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.
(Am J Vet Res 2005;66:330–341)