4-hydroxy-2-nonenal and Pancreatitis--Chronic

Chronic pancreatitis (CP) is a heterogeneous disease defined as chronic inflammatory changes of the pancreatic tissue caused by variety of aetiologies. Oxidative stress accompanying the inflammatory processes has been suggested as an important factor contributing to CP development. The aim of this study was to determine levels of lipid peroxidation products malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE), together with nitrites and the total antioxidant capacity in the plasma of patients with CP and control subjects.. One hundred and five patients with chronic pancreatitis and twenty seven healthy controls were included into this study. Levels of MDA and 4-HNE were analyzed using high-performance liquid chromatography. The total antioxidant capacity of plasma against peroxyl radicals was evaluated using chemiluminescent determination. Nitrites were determined using Griess reaction. Biochemical and haematological parameters were measured by standard methods.. The plasma levels of both MDA and 4-HNE, together with the plasma levels of nitrites, were significantly higher in CP patients, compared to healthy controls. The total antioxidant capacity did not differ significantly. Biochemical parameters were in the normal range. The MDA and 4-HNE levels correlated positively with the levels of high-density lipoprotein cholesterol. Nitrite levels correlated positively with C-reactive protein, total white blood cells, and triglycerides.. The significantly increased plasma levels of MDA, 4-HNE, and nitrites indicate that oxidative stress is present in patients with CP and that it may play a role in initiation and maintenance of inflammation within the pancreatic tissue in CP patients.

Topics: Adult; Aldehydes; Antioxidants; C-Reactive Protein; Cholesterol, HDL; Chromatography, High Pressure Liquid; Female; Humans; Luminescent Measurements; Male; Malondialdehyde; Middle Aged; Nitrites; Oxidative Stress; Pancreatitis, Chronic; Peroxides; Triglycerides

Chronic inflammatory processes produce an excess of ROS and DNA-reactive aldehydes from lipid peroxidation (LPO), such as trans-4-hydroxy-2-nonenal (HNE) and malondialdehyde (MDA), which can modify cellular macromolecules and drive to malignancy. Etheno-modified DNA bases are generated inter alia by reaction of DNA with the major LPO product, HNE. We are investigating steady-state levels of etheno-DNA adducts in organs with diseases related to persistent inflammatory processes that can lead to malignancies. We have developed ultrasensitive and specific methods for the detection of etheno-DNA base adducts in human tissues and in urine. Etheno-DNA adduct levels were found to be significantly elevated in the affected organs of subjects with chronic pancreatitis, ulcerative colitis and Crohn's disease. When patients with alcohol abuse-related hepatitis, fatty liver, fibrosis and cirrhosis were compared with asymptomatic livers, excess hepatic DNA damage was seen in the three latter patient groups. Etheno-deoxyadenosine excreted in urine was measured in HBV-infected patients diagnosed with chronic hepatitis, cirrhosis and hepatocellular carcinoma. As compared to controls, these patients had up to 90-fold increased urinary levels. Impaired or imbalanced DNA-repair pathways may influence the steady-state levels of etheno-DNA adducts in inflamed tissues. In conclusion, etheno-DNA adducts may serve as potential lead markers for assessing progression of inflammatory cancer-prone diseases. If so, the efficacy of human chemopreventive interventions for malignant disease prevention could be verified.

Topics: Aldehydes; Cross-Linking Reagents; DNA Adducts; DNA Damage; Ethanol; Humans; Inflammation; Inflammatory Bowel Diseases; Lipid Peroxidation; Liver; Malondialdehyde; Molecular Structure; Neoplasms; Oxidative Stress; Pancreatitis, Chronic; Risk Factors