ubiquinone and Cholestasis

The aim of these investigations was to establish the secretion of ubiquinone Q10 (UQ10) in bile of sheep under glucose-induced cholestasis. Experiments were performed on 9 cannulated sheep divided into three groups: I-infused with sodium taurocholate, II-with Na-taurocholate plus glucose, III-with Na-taurocholate and glucose plus propranolol, phentolamine and atropine. Infusion of glucose increased plasma glucose concentration from 3.89 +/- 0.593 mM/l to 12.69 +/- 0.852 mM/l in 90 min and produced elevation of plasma insulin from 124.68 +/- 1.984 to 839.54 +/- 29.212 pM/l. Employment of blocking agents reduced insulin release to maximum 685.71 +/- 50.087 pM/l in 90 min. Under infusion of Na-taurocholate, bile flow averaged 14.016 +/- 0.706 microl/min/kg b wt. In the second group, bile flow decreased to 7.08 +/- 0.59 microl/min/kg b wt. in 90 min, and reached 11.25 +/- 0.25 microl/min/kg b wt in 240 min. Addition of the blocking agents in the third group, resulted in a significant (p < 0.05) decrease in bile flow to 3.733 +/- 0.680 microl/min/kg b wt in 105 min. This reduction of bile flow occurred with significant (p < 0.05) reduction of bile acids secretion that averaged 0.032 +/- 0.087 mM/min/kg in the first hour after glucose infusion and was maintained to the end of the experiment. Marked (p < 0.05) increase in UQ10 secretion was observed in both experimental groups. Maximum values of UQ10 secretion were obtained during the second hour of the experiment and averaged 0.449 +/- 0.196ng/min/kg b wt in the second, and 0.338 +/- 0.184ng/min/kg b wt in the third group of animals. Because at the end of the experiment UQ10 secretion gradually decreased we have concluded that free radicals generated during cholestasis lead to reduction of endogenous antioxidant capacity.

Topics: Animals; Bile; Bile Acids and Salts; Blood Glucose; Cholestasis; Coenzymes; Glucose; Hyperglycemia; Insulin; Liver; Sheep; Sheep Diseases; Taurocholic Acid; Ubiquinone

The purpose of the present study was to elucidate the effect of hepatic reflow following ischemia on the remnant liver after hepatectomy with occluded hepatic blood inflow in dogs with obstructive jaundice. When 40% hepatectomy was performed with 10-min occlusion of hepatic blood inflow in dogs with obstructive jaundice, the lipid peroxide content in the remnant liver increased significantly, together with a reduction in superoxide dismutase (SOD)-like activity. The levels of endotoxin and beta-N-acetyl hexosaminase (NAH) in peripheral blood also increased. The phagocytic index increased transiently after 30 min, followed by a marked decrease after 3h. Histologically, degeneration and necrosis of the hepatic parenchymal cells were demonstrated, and survival rate at 7 days was only 23.1%. With the administration of coenzyme Q10 (CoQ10) or styrene-co-maleic acid SOD (SM-SOD), these phenomena were significantly inhibited, and the survival rate improved. After hepatectomy, Kupffer cells in the remnant liver were activated by increased endotoxin levels in the portal vein, inducing the production of free radicals, which, in turn, damaged the Kupffer cells by reducing endotoxin clearance. Finally, the impaired functional reserve in the remnant liver provoked liver failure. The administration of CoQ10 or SM-SOD prevented the occurrence of these phenomena triggered by the free radicals generated by Kupffer cells, stimulated by endotoxin in the portal vein.

Topics: Animals; beta-N-Acetylhexosaminidases; Cholestasis; Coenzymes; Dogs; Endotoxins; Female; Free Radicals; Hepatectomy; Kupffer Cells; Lipid Peroxides; Liver; Male; Phagocytosis; Polystyrenes; Reperfusion Injury; Superoxide Dismutase; Survival Rate; Ubiquinone

Lipid peroxidation and antioxidative mechanisms were investigated in liver mitochondria from bile duct ligated rats (BDL rats) and correlated with the activity of enzyme complexes of the electron transport chain. In comparison to pair-fed control rats, BDL rats had increased concentrations of thiobarbituric acid reacting substances (TBARS) per gram of liver and per milligram of mitochondrial protein 3, 7, 14, and 28 days after surgery. The hepatic glutathione (GSH) content was decreased in BDL rats 28 days after surgery when expressed per gram of liver but equal between BDL and control rats when expressed per liver. The mitochondrial GSH content was decreased in BDL rats by 20% to 33% from day 7 after surgery. The concentrations of ubiquinone-9 and ubiquinone-10, substances involved in electron transport and efficient antioxidants, were both decreased in BDL rats 14 and 28 days after surgery per gram of liver and per milligram of mitochondrial protein. When expressed per liver, ubiquinone-9 was decreased in BDL rats from day 7 after surgery. In comparison with controls, the decrease in total mitochondrial ubiquinone content in BDL rats averaged 52% 14 days and 38% 28 days after surgery. The activity of the succinate:ferricytochrome c oxidoreductase (complexes II and III of the electron transport chain) was decreased in BDL rats at days 7, 14, and 28 after surgery, and the activity of the ferrocytochrome c:oxygen oxidoreductase (complex IV) was reduced at 14 and 28 days after surgery. The mitochondrial concentration of TBARS showed a negative and the concentrations of GSH and ubiquinone a positive correlation with the activity of the succinate:ferricytochrome c oxidoreductase.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Antioxidants; Bile Ducts; Cholestasis; Electron Transport; Electron Transport Complex II; Electron Transport Complex III; Electron Transport Complex IV; Glutathione; Ligation; Lipid Peroxidation; Male; Mitochondria, Liver; Multienzyme Complexes; Oxidoreductases; Rats; Rats, Sprague-Dawley; Succinate Dehydrogenase; Thiobarbituric Acid Reactive Substances; Ubiquinone

To elucidate the mechanism of liver mitochondrial dysfunction induced by obstructive jaundice, the following experiments were performed. In vivo study: Using Wistar male rats, bile ducts were ligated, and serum levels of total bilirubin (T-Bil), GOT, GPT, mitochondrial GOT (mGOT) and total bile acids (TBA) were measured at 3 and 7 days after the ligation. Then, the liver was isolated to determine mitochondrial functions and to measure the content of fatty acids in mitochondrial phospholipids by high performance liquid chromatography. The levels of T-Bil, GOT, GPT, mGOT and TBA were elevated by the bile duct ligation. Mitochondrial functions were deteriorated, and contents of arachidonic acid, palmitic acid and stearic acid in mitochondrial phospholipids decreased. Pretreatment with coenzyme Q10 (E-0216, CoQ10), an antidetergent agent, prevented not only the development of mitochondrial dysfunction and the decrease in mitochondrial phospholipids but also the elevation of GOT, GPT, and mGOT although CoQ10 did not prevent the elevation of T-Bil and TBA levels. In vitro study: Using intact rat liver mitochondria, the effect of taurocholic acid (TCA), one of the physiological bile salts, on the mitochondrial function and on mitochondrial phospholipids was examined. Incubation of mitochondria with TCA induced a dose-dependent deterioration of mitochondrial function and the increase in the content of solubilized phospholipids. The protective effect of CoQ10 was also observed in the in vitro study. These results indicate that degradation of mitochondrial phospholipids by bile acids is responsible for the early phase of liver dysfunction induced by obstructive jaundice.

Topics: Alanine Transaminase; Animals; Aspartate Aminotransferases; Bile Acids and Salts; Bilirubin; Cholestasis; Male; Mitochondria, Liver; Phospholipids; Rats; Rats, Inbred Strains; Taurocholic Acid; Ubiquinone