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

To gain further insight into the mechanisms inducing the protective effect of chloroquine, its influence on the activation of MAPK signaling pathways was studied. It was recently demonstrated that the activation of MAP kinase pathways have a major role in liver I/R injury. 25 Chloroquine inhibits these signaling pathways in monocytes, macrophages and epithelial cells. 13, 31, 32 Chloroquine inhibited the activation of p38 and ERK, leading to the suppression of cytokine production caused by CpG DNA. 13, 32 In this study, we was protective in hepatocytes. 33 Conversely, JNK activation is a deleterious even in hypoxic hepatocytes via the mitochondrial permeability transition (MPT), and inhibition of JNK activation decreases both necrosis and apoptosis in liver I/R. 34 Taken together, these data suggest that modulating of MAP kinase activation is also involved in the hepatic protective effects of chloroquine.