S 1. Graph data as supporting information.

Hemorrhagic shock and resuscitation (H/R) induce hepatic injury and strong inflammatory changes. Chronic ethanol (EtOH) abuse worsens pathophysiological derangements after H/R. Here, the underlying mechanisms involve JNK and NF-κB activation. In our previous studies, we have shown that inhibiting JNK with a cell-penetrating, protease-resistant peptide D-JNKI-1 after H/R in mice with healthy livers ameliorated H/R-induced harmful changes. In this study, we analyzed if JNK inhibition by D-JNKI-1 in chronically EtOH-fed mice after hemorrhagic shock prior to the onset of resuscitation also confers protection. Our findings show that JNK inhibition is protective only in not pre-harmed liver after H/R. Moreover, the pronounced H/R-induced liver damage in mice being chronically fed with ethanol cannot be prevented by JNK inhibition after H/R and seems to be under the control of NF-ĸB.