Evidence that S-adenosyl-L-methionine diastereoisomers may reduce ischaemia-reperfusion injury by interacting with purinoceptors in isolated rat liver

摘要

Mechanisms underlying the haemodynamic activity of diastereoisomers of S-adenosyl-L-methionine (SAM) were investigated using inhibitors of purinoceptors and nitric oxide(NO) synthase in perfused rat livers damaged by sequential 24 h cold and 20 min rewarming ischaemia + reperfusion. Stored livers were flushed with 10 ml saline alone(control) or with added (R,S) or (S,S)SAM (100 μM) and reperfused in the absence (control) or presence of 10 μM 8-phenyltheophylline (8-PT) or 100 μM L-N-monomethylarginine(L-NMMA). Both SAM diastereoisomers rapidly increased blood flow and bile production versus controls (P<0.001) but the (R,S) isomer induced greater increases in blood flow and the (S,S) isomer greater increases in bile production: 625 versus 596 versus 518 ml blood flow and 100 versus 119 versus 56 mg bile production per g liver over 3 h in (R,S),(S,S) and control, respectively.