Moderate hypothermia (cooling) of the liver to ameliorate paracetamol-induced liver injury has gained momentum over the years. However, the invasive procedures available so far have rendered it impractical in a clinical setting. Besides being invasive: they also result in undesirable side effects. But the tides may change with this new format of applying pulsed cooling targeted to the liver in a non-invasive manner. We highlight the ground-breaking results of Yeong Lan T et al. in their quest to demonstrate a non-invasive model for inducing localised cooling to avert liver toxicity.
Yeong Lan T and colleagues applied moderate hypothermia (32°C) to the liver of mice following exposure to 300mg/kg dose of paracetamol by cooling the skin overlying the liver intermittently in pulses of 15 minutes each – using ice packs. They maintained the core body temperature of the study mice throughout the trial by using heat pads at 37°C. Yeong Lan T et al. exposed some mice to paracetamol without hypothermia to the liver. These acted as controls. They monitored the extent of liver injury through liver function tests, liver histology, and total weight change.
At the end of the study, the mice that had undergone pulsed cooling (moderate hypothermia) showed little to no liver injury. The researchers demonstrated that modest hypothermia could ameliorate paracetamol-induced drug injury. During the study, the liver enzyme levels decreased by more than two-thirds in the experimental mice. The centrilobular necrosis in paracetamol-induced liver injury was unremarkable in the interventional mice. The livers of these mice, however, showed reduced glycogen compared to the control group. The mice with cooled livers also gained weight because they fed better than those with liver injury without any intervention.
The results of this study are fascinating for several reasons. First, there’s a non-invasive way of averting the disastrous effects of paracetamol-induced liver injury that we can apply locally and to the anatomical site of the liver using the overlying skin. Second, it is yet another novel format of using selective hypothermia to halt the inflammatory processes at the cellular level for specific organs – extensively used in traumatic brain injury and sports-related soft tissue injuries, especially for the knees, shoulders, and ankles. Finally, the fact that we can translate this novel research into a clinical procedure is incredible.
Yeong Lan T et al.’s research findings appeared in Nature – scientific reports journal. You can read about it from here.