Dual role of chloroquine in liver ischemia reperfusion injury: reduction of liver damage in early phase, but aggravation in late phase

Fang, H; Liu, A; Dahmen, U; Dirsch, O

Chloroquine treatment modulates liver I/R-induced inflammatory signaling pathways. Among the most proximal events in I/R is the activation of mitogen-activated protein (MAP) kinases. 25 To determine if chloroquine pre-treatment influenced MAP kinase activation, we assessed phosphorylation of extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK) and p38. As shown in Figure 4 , after I/R, phosphorylation p38 and JNK was increased in vehicle-treated rats. In contrast, phosphorlation of JNK was decreased, whereas phosphorylation of p38 was increased in chloroquine-injected rats. Phosphorylation of ERK was increased at 0.5 h, decreased at 6 h and then recovered thereafter. This dephosphorylation was partially prevented by chloroquine treatment. Treatment with chloroquine did not affect total cellular levels of JNK, p38 and ERK. These data suggest that chloroquine could act upstream of MAP kinase activation.