Elevated protein carbonyls as plasma markers of oxidative stress in acute pancreatitis

Abstract

Experimental studies have demonstrated that protein and lipid oxidation is a feature of acute pancreatitis and that antioxidant pretreatment can ameliorate the severity of the disease. Justification for a clinical trial of antioxidant therapy requires stronger evidence for oxidative stress in patients. To determine if oxidative stress is evident in patients with acute pancreatitis on admission to hospital, if it increases after admission and if it is related to disease severity. Measurement of plasma concentrations of protein carbonyls and malondialdehyde as markers of protein oxidation and lipid peroxidation, respectively, in a consecutive series of 85 patients with acute pancreatitis 0, 2 and 5 days after admission. Patients with acute pancreatitis had significantly increased concentrations of protein carbonyls in plasma on recruitment (median 27 h after the onset of symptoms) that persisted over 5 days. Protein carbonyls were higher in severe compared with mild disease (median 0.099 and 0.043 nmol/mg protein, respectively, p = 0.0016). They were higher at day 0 in patients recruited with more established pancreatitis than in those presenting early. No increases in malondialdehyde were seen. Receiver operator characteristic curve analysis demonstrated that protein carbonyls at day 0 were comparable with C-reactive protein at predicting pancreatitis severity. Our demonstration of substantial protein oxidation provides further evidence for oxidative stress in patients with severe pancreatitis. Our results suggest that there could be a window for early antioxidant intervention and that protein carbonyls could be a useful plasma marker of oxidative injury.