4-hydroxy-2-nonenal and Pancreatic-Diseases

To provide more detailed information on the roles of lipid peroxidation in the pathogenesis of chronic pancreatic injuries in a pre-clinical rat model.. Totally 72 rats were divided into 6 groups (12 in each group) Rats in 5 experimental groups (n = 12) were fed with a high-fat diet (1% cholesterol, 10% lard, 0.3% sodium tauroglycocholate, 87.3% standard rodent chow as the control group) for 2, 4, 6, 10 and 16 weeks, respectively. Morphological studies in the pancreas tissue samples from rats were investigated by using various histological methods. Pancreatic stellate cells (PSCs) were identified by immunohistochemical staining for Desmin and α-smooth muscle actin (α-SMA). The expression of the lipid peroxidation was detected by immunostaining for 4-hydroxy-2-nonenal (4-HNE) and thromboxane A2 receptor (TxA2r). The co-localization of α-SMA and 4-HNE or α-SMA and TxA2r in PSCs was also analyzed in this study.. Pancreatic cells with positive staining for Desmin and α-SMA in HFD rats were distributed in a more extensive way when compared to that in the control group. The levels of pancreatic 4-HNE and TxA2r were increased in rats from HFD groups significantly. The co-localization of 4-HNE and TxA2r were also found within activated PSCs in both of groups.. The results showed that a chronic HFD feeding may increase the lipid peroxidation process and collagen synthesis through a critical signaling pathway of activated PSCs following pancreatic injuries in rats.

Topics: Actins; Aldehydes; Animals; Collagen; Desmin; Diet, High-Fat; Disease Models, Animal; Lipid Peroxidation; Male; Oxidative Stress; Pancreas; Pancreatic Diseases; Rats; Rats, Sprague-Dawley; Receptors, Thromboxane A2, Prostaglandin H2

Reproduction of pancreatic iron overload in an animal model has been difficult to achieve primarily because of the first-pass extraction of iron by the liver. We hypothesized that portacaval shunting would avoid this hepatic phenomenon and increase pancreatic iron deposition. An end-to-side portacaval shunt was surgically created in male Sprague-Dawley rats, and they were subsequently fed a carbonyl iron-supplemented diet for 17 weeks. This resulted in marked iron accumulation in the pancreas (1621 +/- 188 micrograms/g) compared to minimal deposition in sham-operated rats fed the same diet (138 +/- 53 micrograms/g). Iron deposition in the acinar and centroacinar cells was confirmed histologically by Gomori staining, as well as by ultrastructural examination. Iron overloading was associated with enhanced oxidative stress evidenced by a twofold increase in the levels of glutathione disulfide and thiobarbituric acid-reactive substances. Also, adducts of proteins with malondialdehyde and 4-hydroxynonenal were demonstrated in acinar and ductal cells. Other apparent consequences of iron overload were a 50% reduction in pancreatic amylase content and a decrease in pancreatic protein concentration. These hypotrophic changes were associated with a reduced mass of zymogen granules in the acinar cells noted histologically. Our results show that a combination of portacaval shunting and carbonyl iron feeding achieve pancreatic iron overload and support the role of oxidative stress in the pathogenesis of iron-induced damage in the pancreas.

Topics: Aldehydes; Animals; Dietary Supplements; Disease Models, Animal; Immunohistochemistry; Iron Overload; Iron, Dietary; Male; Malondialdehyde; Oxidative Stress; Pancreas; Pancreatic Diseases; Portacaval Shunt, Surgical; Rats; Rats, Sprague-Dawley; Thiobarbituric Acid Reactive Substances

To assess parameters of lipid peroxidation in bile of patients with hepatobiliary and pancreatic diseases.. F2-isoprostanes (F2-IPs) and 4-hydroxynonenal (4-HNE) were measured in bile collected during 31 ERCP procedures using gas chromatography/mass spectrometry.. In 11 subjects with normal ERCP (controls), bile contained significant amounts of F2-IPs (188 +/- 27 pg/ml) and 4-HNE (37.5 +/- 8.0 ng/ml). In 10 individuals with bile duct stones, there was a 3-fold increase of F2-IPs (523 +/- 129 pg/ml; p < 0.05) and a 2.5-fold increase of 4-HNE (89.6 +/- 18.0 ng/ml; p < 0.05). In 10 patients with various pancreatic diseases, bile F2-IPs were also enhanced (545 +/- 112 pg/ml; p < 0.01). There was no significant change in alpha-tocopherol, whereas beta-carotene was decreased in biliary tract and pancreatic diseases (p < 0.05). Results of serum liver tests were normal with the exception of bilirubin, which was increased together with alkaline phosphatase. Concentrations of total lipids, phospholipids, and cholesterol did not differ significantly between the three groups.. These data provide the first evidence in humans supporting the role of oxidative stress in the pathogenesis of biliary and pancreatic disease.

Topics: Aged; Aldehydes; Analysis of Variance; beta Carotene; Bile; Bile Duct Diseases; Cholangiopancreatography, Endoscopic Retrograde; Cholelithiasis; Chromatography, High Pressure Liquid; Dinoprost; Gas Chromatography-Mass Spectrometry; Humans; Middle Aged; Pancreatic Diseases; Vitamin E