Ethanol Potentiates the Acute Fatty Infiltration of Liver Caused by Burn Injury: Prevention by Insulin Treatment

Burn injury is a significant and severe representation of critical illness. Nearly, 50% of patients admitted to hospitals for burn injuries have detectable levels of ethanol in their circulations and these patients have poorer clinical outcomes than burned individuals without measurable circulating ethanol. We report here data on a clinically relevant form of hepatic injury, the development of microvesicular steatosis, in a murine model wherein animals were either given ethanol or saline, and were subjected to burn or sham injury. Because better glycemic control with insulin has been shown in clinical studies to impart major clinical benefit, an additional group of burn ethanol animals were treated with insulin. Insulin significantly reduced blood glucose in injured animals to levels no different from those seen in animals that were neither ethanol exposed nor burned. A single intraperitoneal injection of ethanol was insufficient to raise blood alanine aminotransferase (ALT), measured as an index of liver injury. However, burn injury led to significant increases in ALT at 24 and 48 hours, which had returned to preinjury levels by 7 days. This ALT rise was completely prevented with insulin treatment. A single injection of ethanol did not evoke increased microvesicular steatosis but did potentiate the ability of burn to do so at 24 hours after injury. The burn induced increase in microvesicular steatosis was also seen at 48 hours, but had subsided by 7 days. The increased microvesicular steatosis was prevented by insulin therapy. Thus, ethanol potentiates the ability of burn to cause acute liver injury, which is completely preventable by insulin therapy. These findings may have substantial clinical significance and suggest this model may be Useful for the study of the mechanisms of hepatic injury as well as the mechanisms, probably multiple, of insulin action in this setting. (J Burn Care Res 2009;30:482-488)