In vivo demonstration of a novel non-invasive model for inducing localized hypothermia to ameliorate hepatotoxicity

Abstract

Moderate hypothermia (32 °C) has been previously shown to ameliorate drug-induced liver injuries in vitro. However, there are concerns regarding its clinical relevance as it remains a challenge to perform selective liver cooling in a non-invasive manner. To reconcile this dilemma, we propose the use of pulsed cooling for regional hypothermic conditioning in liver. This involves intermittent cooling applied in pulses of 15 min each, with a one-hour recovery interval between pulses. Cooling is achieved by applying ice packs to the cutaneous region overlying the liver. Through an in vivo C57BL/6NTac mouse study, we demonstrated the feasibility of attaining localized hypothermia close to the liver while maintaining core body temperature. This has successfully ameliorated acetaminophen-induced liver injury based on the liver function tests, liver histology and total weight change. Collectively, we provide a proof of concept for pulsed external localized cooling as being clinically actionable to perform induced selective hypothermia.