S-Adenosylmethionine Inhibits Plasminogen-Activating Inhibitor-1 and Protects Male Mice From FOLFOX-Induced Liver Injury

FOLFOX treatment increased hepatocyte PAI-1 expression and liver injury, which were not observed in germline PAI-1 deficiency. Hepatocytes secrete PAI-1 to exert autocrine and paracrine effects to activate Kupffer cells and liver sinusoidal endothelial cells. SAMe protects against FOLFOX-mediated liver injury in part by inhibiting NF-κB activation and PAI-1 induction.