Ai. Galan et al., Role of S-adenosylmethionine on the hepatobiliary homeostasis of glutathione during cyclosporine A treatment, J PHYSIOL B, 56(3), 2000, pp. 189-199
The effects of cyclosporine A (CyA) treatment on the hepatic content and bi
liary output of reduced (GSH) and oxidized (GSSG) glutathione and lipid per
oxidation in the liver, and the ability of S-adenosylmethionine (SAMe) to a
ntagonize the CyA-induced alterations were studied in male Wistar rats. To
evaluate the efficacy of SAMe, three CyA and SAMe protocols were used: cotr
eatment with SAMe plus CyA, pretreatment with SAMe before starting cotreatm
ent, and post-treatment with SAMe after beginning treatment with CyA alone.
CyA treatment for one and four weeks depleted liver GSH, decreased the GSH
/GSSG ratio and significantly reduced GSH and GSSG biliary concentrations a
nd secretion rates. Additionally, long-term treatment enhanced lipid peroxi
dation. By contrast, when the rag were treated with CyA plus SAMe using any
of the administration protocols, SAMe was seen to be efficient in antagoni
zing the GSH hepatic depletion, the changes in hepatic GSH/GSSG ratio and t
he increase induced by CBA in lipid peroxidation. Furthermore, SAMe also ab
olished the effects of CyA on the biliary secretion rates of GSH and GSSG.
The efficacy of SAMe was similar, regardless of the administration protocol
s used. In conclusion, our results clearly demonstrate that SAMe is good fo
r preventing, antagonizing and reversing the CyA-induced alterations in the
hepatobiliary homeostasis of glutathione.