8-epi-prostaglandin-f2alpha and Liver-Diseases

Parenteral nutrition-associated liver disease (PNALD) continues to cause morbidity and mortality for neonates with intestinal failure. Lipid peroxidation is one potential etiological factor. This study was designed to test if supplementing vitamin E into conventional soy-based lipid would reduce the risk of PNALD.. Sixteen piglets, aged 2-5 days and weighing 1.8-2.5 kg, were randomized to parenteral nutrition (PN) with soy lipid (SO, n = 8) or the same lipid plus α-tocopherol, the most bioactive form of vitamin E (SO+E, n = 8). After 17 days, bile flow, liver chemistry, gene expression associated with bile acid metabolism, and bile acid composition were assessed. C-reactive protein (CRP) and oxidative stress markers, including plasma 8-isoprostane, were measured. All results were compared with a sow-reared control group (CON).. Comparing PN-treated groups, SO vs SO+E mean bile flow (5.91 vs 5.54 µL/g liver; P = .83), serum bile acid concentration (39.2 vs 26.6 µmol/L; P = .12), and total bilirubin (35.2 vs 26.9 µmol/L; P = .56) were not different. Gene expression related to bile acid metabolism and bile composition was not different between PN groups. There was no difference in CRP (41.8 vs 36.8 µg/mL; P = .22) or in plasma 8-isoprostane (27.9 vs 26.1 pg/mL; P = .77).. In term neonatal piglets, supplemental vitamin E did not prevent cholestasis. Additional vitamin E was not associated with reduced inflammation or oxidative stress. The benefit of supplementing vitamin E into conventional lipid, vs adding fish oil, to prevent early onset of PNALD requires further clarification.

Topics: Alanine Transaminase; Alkaline Phosphatase; alpha-Tocopherol; Animals; Animals, Newborn; Bile Acids and Salts; Bilirubin; Biomarkers; C-Reactive Protein; Cholestasis; Dinoprost; Disease Models, Animal; Fat Emulsions, Intravenous; Female; gamma-Glutamyltransferase; Liver Diseases; Oxidative Stress; Parenteral Nutrition; Soybean Oil; Swine

In the liver, eNOS appears to have a central role in protecting against ischemia/reperfusion (I/R) injury. We hypothesized that tetrahydrobiopterin (BH4) would protect livers subjected to I/R injury by coupling with eNOS.. Chinese Kun Ming (KM) mice were subjected to 60 min of 70% hepatic ischemia 30 min after the administration of BH4 or saline. After reperfusion, survival was evaluated. The histologic appearance and ALT, BH4, nitrite/nitrate, 8-isoprostane, and eNOS protein expression levels were measured.. The 1-wk survival rate was 66.67% in the BH4 group and 33.33% in the saline group. The serum ALT values in the BH4 group 1, 3, 6, 12, and 24 h after reperfusion were significantly lower than those of the saline group. A histologic examination of the liver revealed only a small necrotic area in the BH4 group as opposed to massive necrosis in the saline group. The percentage values of the hepatic necrotic area 24 h after reperfusion were significantly less for the BH4 group than for the saline group. The nitrite/nitrate levels in the liver tissue were significantly increased by ~2-fold in the BH4 group compared with the saline group. The free radical indicator 8-isoprostane was reduced approximately 50% in the BH4 group compared with the saline group. Western blotting showed that the level of eNOS protein between the groups was not significantly different.. BH4 significantly improved the survival rate by reducing liver failure. This was supported by the histologic findings, and the mechanism was explored. According to the results, we suggest that BH4 prevents liver damage from I/R injury by attenuating reactive oxygen species and increasing NO synthesis, and might provide a novel and promising therapeutic option for preventing I/R injury.

Topics: Alanine Transaminase; Animals; Biopterins; Delayed Graft Function; Dinoprost; Liver; Liver Diseases; Liver Transplantation; Mice; Mice, Inbred Strains; Nitrates; Nitric Oxide Synthase Type III; Reperfusion Injury; Superoxides; Vitamin B 12

Many post-operative patients with biliary atresia (BA) suffer from liver dysfunction, such as chronic inflammation even without jaundice after a Kasai's hepatic portoenterostomy.. The presence and degree of oxidative stress were evaluated in the post-operative patients with BA. Twelve outpatients who underwent a Kasai's hepatic portoenterostomy were evaluated. The active oxygen products, the rate of bioantioxidant, the markers of oxidative stress, and the degree of hepatic oxidative stress were examined by immunohistochemical staining of biopsied specimens.. All of the oxidative stress markers in the post-operative patients with BA increased in comparison to those in the controls. Moreover, 8-OHdG immunohistochemical staining was positive in 84+/-4.8% in hepatic cells in the portal area in the post-operative patients with BA.. The post-operative patients with BA were under increased oxidative stress, even if their liver dysfunction was mild without jaundice. Antioxidant therapy might be necessary to decrease of oxidative stress in the post-operative patients with BA.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Alanine Transaminase; Biliary Atresia; Biomarkers; Case-Control Studies; Child; Child, Preschool; Collagen Type IV; Deoxyguanosine; Dinoprost; Female; gamma-Glutamyltransferase; Humans; Immunohistochemistry; Infant; Insulin-Like Growth Factor I; Liver Diseases; Male; Oxidative Stress; Portoenterostomy, Hepatic; Postoperative Period; Superoxide Dismutase

Topics: Adult; Aged; Arginine; Dinoprost; F2-Isoprostanes; Female; Humans; Kidney Failure, Chronic; Liver Diseases; Male; Middle Aged