HYPOTHERMIC CONDITIONING IN ACUTE DRUG-INDUCED LIVER TOXICITY

Abstract

Therapeutic hypothermia (TH) involves a downshift of core body temperature from its physiological range (36.5-37.5 °C) to below 35 °C, to achieve specific therapeutic outcomes. Its neuroprotective role in cardiac arrest is especially prominent and well-accepted. Therefore, we seek to expand its therapeutic profile into the domains of acute drug-induced liver toxicity – with limited management strategies, and it could deteriorate drastically with potential fatality. To do so, we began with an inquiry on its hepatoprotective potential in a classical acetaminophen-induced liver injury model. The optimal hypothermic window for attenuation of liver damage was uncovered, along with a detailed mechanistic elucidation in vitro, involving cold shock protein-dependent and -independent pathways. Finally, we proposed and demonstrated the potential of a novel pulsed cooling notion to conduct localized liver cooling in vivo in a non-invasive manner. Together, all these redefined the limits of TH and instilled new outlook to its potential hepatoprotective application.