Figure 12

Schematic representation of critical changes in the liver in mice exposed to GWI-related substances and subsequently challenged with EtOH in the absence or presence of PLX3397 inhibitor of CSF1R of macrophages. Mice that were exposed to a combination of PER and PB followed by a period of recovery, exhibited significant levels of hepatic microsteatosis and chronic low-grade inflammation and priming of the immune cells in the liver. Indeed, GWI mice that underwent chronic single binge of EtOH (a second hit on the liver), suffered increased liver damage as compared to Naïve mice with EtOH. Treatment with PLX3397, a small molecule that depletes macrophages, reduced inflammation and microsteatosis in mice exposed to GWI compared to Naïve controls. Moreover, GWI mice treated with PLX3397 prior to EtOH binging, decreased the level of steatosis, fibrosis and ductular reaction, compared to GWI mice that did not receive PLX3397.