S-adenosylmethionine protects post-ischemic mitochondrial injury in rat liver

S-adenosylmethionine (SAM) is a thiol-containing compound with known therapeutic affects on cholestasis and hepatotoxicity. The aim of this study was to investigate the effect of SAM on the prevention of mitochondrial injury induced by hepatic ischemia and reperfusion.

Rats were subjected to 60 min of hepatic ischemia and 1 and 5 h of reperfusion. 2 h prior to ischemia, the animals received either vehicle or SAM intraperitoneally. In the vehicle-treated ischemic animals, serum aspartate aminotransferase levels increased at 1 h and again at 5 h of reperfusion and were reduced by SAM pre-treatment. Similarly, mitochondrial lipid peroxidation was elevated in the vehicle-treated group, but this elevation was attenuated by SAM. In contrast, mitochondrial glutamate dehydrogenase activity and reduced glutathione concentration both decreased in the vehicle-treated group, and this decrease was also inhibited by SAM. Hepatic ATP levels in the vehicle-treated rats were found to be 42% lower 5 h after reperfusion, however, treatment with SAM elevated these ATP levels. SAM treatment increased the concentration of adenosine but inhibited the accumulation of hypoxanthine in the ischemic liver.

SAM protects against mitochondrial injury, which prevents mitochondrial oxidant stress and improves ischemia-induced hepatic energy metabolism.