dinoprost and Liver-Diseases

Hepatic injury through carbon tetrachloride (CCl(4)) induced lipid peroxidation is well known and has been extensively used in the experimental models to understand the cellular mechanisms behind oxidative damage and further to evaluate the therapeutic potential of drugs and dietary antioxidants. Many of these methods that have often been used to study free-radical induced lipid peroxidation suffer methodological discrepancies when considering the measurements in vivo. Recent discovery of isoprostanes, non-enzymatically derived prostaglandin F(2)-like compounds, unfolded a new era of determination of oxidant stress in vivo. Cyclooxygenase (COX) catalysed prostaglandins formation from arachidonic acid and their involvement in inflammation is well known. This review mainly focuses on the formation of non-enzymatically and enzymatically catalysed eicosanoids, namely the isoprostanes and prostaglandin F(2alpha) (PGF(2alpha)), following CCl(4) treatment in animals and their regulation by antioxidants. Both eicosanoids are increased dramatically in the peripheral plasma, urine and/or liver tissues but with diverse kinetics of formation, release and excretion pattern. Free radical and COX-mediated oxidation of arachidonic acid products are intimately associated with experimental hepatotoxicity. Studies suggest that there is a link between initial involvement of oxidative stress and subsequent induction of the COX mediated inflammatory process, which may have an eminent role in the pathogenesis of liver diseases. Antioxidant nutrients have been shown to affect both the formation of isoprostanes and prostaglandin metabolite but the therapeutic values and exact mechanisms of action remain unclear.

Topics: Animals; Antioxidants; Carbon Tetrachloride; Chemical and Drug Induced Liver Injury; Cytochrome P-450 Enzyme System; Dinoprost; Humans; Isoprostanes; Lipid Peroxidation; Lipid Peroxides; Liver Diseases; Oxidative Stress; Prostaglandin-Endoperoxide Synthases; Reactive Oxygen Species

Most of the traditional methods used to assess oxidative stress in clinical setting are non specific, unreliable or inaccurate. Recently, a novel family of prostaglandin F2 isomers, called F2-isoprostanes, produced in vivo by a free radical peroxidation of arachidonic acid, has been described. These compounds may produce physiological or pathological effects due to their ability to alter smooth muscle and platelet functions. The quantification of the two major isoforms (isoprostaglandin F2 alpha type-III and VI) in biological fluids and tissues as markers of lipid peroxidation appears to be an important advance in our ability to explore the role of free radicals in the pathogenesis of human disease.. Urinary excretion of F2-isoprostanes is correlated with age, indicating increased oxidative stress during the normal aging process. High F2-isoprostanes concentration has been described in diseases such as ischemic heart disease, diabetes, Alzheimer's disease and hepatic cirrhosis. The correlation of F2-isoprostane concentrations and human diseases severity in hepatic cirrhosis, cardiac failure and diabetes suggest that these compounds may be of interest as predictive markers.. Preliminary studies suggest the use of F2-isoprostanes as prognosis markers. In addition, F2-isoprostanes quantification offers promising potential as intermediate endpoints for clinical studies of antioxidant therapies.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antioxidants; Biomarkers; Cardiovascular Diseases; Child; Diabetes Mellitus; Dinoprost; Female; Free Radicals; Humans; Hypercholesterolemia; Infant, Newborn; Kidney Transplantation; Lipid Peroxidation; Liver Diseases; Lung Diseases; Male; Middle Aged; Nervous System Diseases; Oxidative Stress; Prognosis; Risk Factors; Smoking

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

The aim of this study was to determine the effects of enrofloxacin (ENR), flunixin meglumine (FM) and dexamethasone (DEX) on antioxidant status and organ damage markers in experimentally-induced endotoxemia. Rats were divided into three groups. To induce endotoxemia, lipopolysaccharide (LPS) was injected into all groups, including the positive control. The two other groups received the following drugs (simultaneously with LPS): ENR + FM + low-dose DEX and ENR + FM + high-dose DEX. After the treatments, blood samples were collected at 0, 1, 2, 4, 6, 8, 12, 24 and 48 h. Oxidative stress parameters were determined by ELISA, while serum organ damage markers were measured by autoanalyser. LSP increased (p < 0.05) malondialdehyde, 13,14-dihydro-15-keto-prostaglandin F(2 alpha) and nitric oxide, while LPS reduced vitamin C. These changes were especially inhibited (p < 0.05) by ENR + FM + high-dose DEX. LPS increased organ damages markers. Cardiac and hepatic damage was not completely inhibited by any treatment, whereas renal damage was inhibited by two treatments. This study suggested that ENR + FM + high-dose DEX is most effective in the LPS-caused oxidative stress and organ damages.

Topics: Animals; Ascorbic Acid; Autoanalysis; Biomarkers; Clonixin; Dexamethasone; Dinoprost; Disease Models, Animal; Drug Therapy, Combination; Enrofloxacin; Enzyme-Linked Immunosorbent Assay; Female; Fluoroquinolones; Heart Diseases; Kidney Diseases; Lipopolysaccharides; Liver Diseases; Male; Malondialdehyde; Multiple Organ Failure; Nitric Oxide; Oxidative Stress; Rats; Rats, Sprague-Dawley; Shock, Septic; Superoxide Dismutase; Time Factors

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

The present study was undertaken to relate wound healing of an internal organ to prostaglandins of the E and F series. A small liver wound was induced by a galvanic cauter via the abdominal route under general anesthesia and prostaglandin E1, E2 and F2alpha were injected twice daily at a dose of 250 microg/kg. Proliferation of the connective tissue in the liver wound was estimated morphometrically 6 days after liver wound infliction. Levels of prostaglandins E2 and F2alpha were measured in the liver wound as well as in normal liver tissue from adjacent lobes using radioimmunoassay. The results show that exogenous prostaglandins of the E-series suppress connective tissue proliferation. Three minutes after the last prostaglandin E2 injection, high prostaglandin concentrations were measured both in the liver wound and in the liver tissue of the adjacent lobe. Prostaglandin F2alpha injections had no effect on wound healing. We believe that the rat thermic liver wound model can be used for different studies on wound healing mechanisms and that prostaglandins of the E-series are involved in wound healing in the specific time period studied.

Topics: Alprostadil; Animals; Cell Division; Connective Tissue; Dinoprost; Dinoprostone; Liver Diseases; Prostaglandins E; Rats; Wounds and Injuries

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

To assess the role of altered renal and systemic production of thromboxane A2 and prostacyclin in the hepatorenal syndrome, urinary excretion of their major renal and extrarenal metabolites was measured in patients with compensated and decompensated liver disease, chronic renal failure, and hepatorenal syndrome. Urinary excretion rates of all prostanoids (renal and extrarenal) were increased in subjects with liver disease compared with normal controls. Moreover, they were considerably higher in subjects with severe hepatic decompensation but good renal function compared with those with hepatorenal syndrome. In contrast, the excretion rate of all metabolites was reduced in patients with chronic renal failure. The excretion rate of all metabolites was markedly elevated during the early stages of hepatorenal syndrome and decreased in parallel with creatinine clearance. When corrected for creatinine clearance, there was a strong correlation between prostanoid excretion and serum bilirubin in subjects with liver disease; there was no difference, however, in the excretion of renal and extrarenal prostanoids between hepatorenal syndrome and severe hepatic decompensation. It is concluded that hepatic decompensation is associated with a progressive increase in prostanoid excretion but that changes in production of prostacyclin or thromboxane A2 are unlikely to be major factors in the pathogenesis of the hepatorenal syndrome.

Topics: Adult; Aged; Ascites; Bilirubin; Creatinine; Dinoprost; Epoprostenol; Female; Hepatorenal Syndrome; Humans; Kidney; Kidney Failure, Chronic; Liver Cirrhosis; Liver Diseases; Male; Middle Aged; Thromboxane A2; Thromboxane B2

Changes in urinary PGE2 and PGF2 alpha excretion in chronic liver diseases were observed in relation to renal hemodynamics and sodium balance. After equilibration on a 110-170-meq sodium diet, daily urine collections were analyzed for PGE2 and PGF2 alpha by a new extraction and radioimmunoassay method. PGE2 was significantly greater in cirrhotics than in healthy subjects and in chronic hepatitis. The value was greater in cirrhotics with ascites than in those without ascites (p less than 0.05). PGF2 alpha did not differ among the groups. In cirrhotics PGE2 was correlated negatively with creatinine clearance (Ccr)(r = -0.76, p less than 0.001). After administration of 200 mg indomethacin, a significant fall in Ccr was seen only in cirrhotics with ascites. The percentage fall in PGE2 after indomethacin correlated with that in Ccr (r = 0.89, p less than 0.05) and with that in urinary sodium excretion (r = 0.68, p less than 0.02). These results suggest that PGE2 is essential in the maintenance of renal function in liver cirrhosis with ascites.

Topics: Adult; Dinoprost; Dinoprostone; Female; Hemodynamics; Hepatitis; Hepatitis, Chronic; Humans; Indomethacin; Kidney; Liver Cirrhosis; Liver Diseases; Male; Middle Aged; Prostaglandins E; Prostaglandins F; Renal Circulation; Renin-Angiotensin System