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

The mechanism of liver damage after I/R has been studied extensively. The signaling events contributing to cellular and tissue damage are diverse and complex, and consist of complex interactions of multiple inflammatory pathways. [3] [4] [5] Proinflammatory cytokines, such as high-mobility group box 1 (HMGB1), tumor necrosis factor (TNF)-a and interleukin (IL)-1b are known to increase in serum and liver tissue on reperfusion and have a pivotal role in the pathophysiology of hepatic I/R injury. [6] [7] [8] [9] Chloroquine, a well-known anti-malaria drug, has also been frequently used in the treatment of inflammatory diseases, including rheumatoid arthritis and systemic lupus erythematodes. 10 It has been suggested that the therapeutic effect of chloroquine in these diseases is related to its immunoregulatory potency. Recent evidences have shown that chloroquine inhibits proinflammatory cytokine production by macrophages or monocytes after stimulation with lipopolysaccharide (LPS) or CpG oligonucleotide (CpG ODN). [11] [12] [13] In vivo, chloroquine protected mice from lethal doses of LPS or CpG ODN through a decrease of proinflammatory cytokine release. 11 Furthermore, chloroquine protected mice from sepsis-induced acute kidney injury and decreased serum inflammatory cytokines levels. 14 Prompted by these results, we hypothesized that chloroquine could also possess anti-inflammatory abilities to protect from or reduce hepatic I/R injury, which is characterized as inflammatory injury.