The role of hepatic cytochrome P-450 in sepsis

Severe sepsis is a common, expensive, and fatal condition with as many deaths annually as those from acute myocardial infarctions. The average cost per case seems to exceed $22,000. The increased morbidity and mortality attributed to sepsis could be due to the lack of our understanding of mediators and factors responsible for early cellular alterations and thus could not be intervened which result in progressive deterioration of cell and organ function and even death. It has been well documented that hepatocellular dysfunction occurs early in sepsis and it contributes to multiple organ failure and ultimately death; however the exact mechanism is poorly understood. We and others have shown that cytochrome P-450 (CYP) enzyme system, a superfamily of heme proteins responsible for the metabolism of a variety of endogenous and exogenous substances, plays a crucial role in the prevention of hepatocellular dysfunction in sepsis. In this review, we describe the alterations of CYP enzymes in the experimental model of sepsis and provide the limited information available in septic and severely injured patients. We also review the potential mechanism for the alterations of CYP enzymes in sepsis. Finally, we highlight the importance of future studies needed to understand the regulation of CYP isoforms to develop therapy for hepatocellular dysfunction in sepsis.