Increased oxidative stress and renal injury in patients with sepsis

Sepsis remains one of the leading causes of death in intensive care units. The early phase of sepsis is characterized by a massive formation of reactive oxygen and nitrogen species such as super oxide and nitric oxide. However, few comprehensive studies on plasma antioxidants have been reported. Increased oxidative stress was confirmed in sepsis patients (n = 18) at the time of hos pitalization by a significant decrease in plasma ascorbic acid and a significant increase in the percentage of oxidized form of coenzyme Q10 in total coenzyme Q10 compared to agematched healthy controls (n = 62). Tissue oxidative damage in patients was suggested by a significant decrease in polyunsaturated fatty acid contents and a significant increase in oleic acid contents in total free fatty acids. Thus, it is reasonable that plasma uric acid (end product of purines) would be significantly elevated. However, uric acid levels were continuously decreased during hospitaliza tion for 7 days, indicating a continuous formation of peroxynitrite. A greater decrease in free cholesterol (FC) compared to cholesterol esters (CE) was observed. Thus, the FC/CE ratio significantly increased, suggesting deficiency of lecithincholesterol acyltrans ferase secreted from the liver. Plasma levels of prosaposin, a coenzyme Q10 binding protein, significantly decreased as com pared to healthy controls. This may be correlated with renal injury in sepsis patients, since the kidney is thought to be a major secretor of prosaposin.