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.
Highlights
Moderate hypothermia (32 °C) has been previously shown to ameliorate drug-induced liver injuries in vitro
We have previously reported on the potential of using moderate hypothermia (32 °C) to ameliorate acetaminophen-induced liver injury (AILI) in vitro[1] and presented various mechanistic insights on the effect of hypothermia in AILI2
Wang et al reported an upregulation of cold shock protein (CSP) expression in the liver following chronic intermittent cold (CIC) exposure[6], where CSP was previously shown to play an imperative role in conferring cytoprotection[1]
Summary
Moderate hypothermia (32 °C) has been previously shown to ameliorate drug-induced liver injuries in vitro. 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. Wang et al reported an upregulation of cold shock protein (CSP) expression in the liver following CIC exposure[6], where CSP was previously shown to play an imperative role in conferring cytoprotection[1] All these reports present intermittent cooling as a viable approach for achieving therapeutic hypothermia in the toxic liver. We attempt to increase the proximity between the liver and the site of cold application to improve the cooling efficiency in a non-invasive manner With this model of a novel, non-invasive pulsed cooling modality, we sought to validate its feasibility and efficacy for the amelioration of acute DILI through an in vivo mouse study. This preliminary study outlines the pursuit for a practical, non-invasive cooling strategy targeted at a specific visceral location
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