Effect of glucose administration on bilirubin excretion in the rabbit

Summary The effect of i.v. infusion of glucose on the hepatic handling of bilirubin was examined in rabbits. A significant increase in the excretion of conjugated bilirubin into the bile was observed, accompanied by a decrease in bilirubinemia. Hepatic bilirubin concentrations were lowered and the UDP-glucose concentrations and liver UDP-glucuronosyl and UDP-glucosyl transferase activities increased.     

The serum levels of unbound bilirubin that induce changes in some brain mitochondrial reactions in newborn guinea-pigs

Bilirubin in different concentrations was injected in newborn guinea-pigs and the following parameters were determined: serum total and unbound bilirubin, whole brain bilirubin content and oxygen consumption, NADH-cytochrome c reductase and ATPase activities in brain mitochondria. The results showed a significant correlation between decreased rates of brain metabolism and the elevation of serum total and unbound bilirubin.     

Proton-induced dismutation of superoxide in aprotic media by bile pigments

Cyclic voltammetry of molecular oxygen in aprotic media (dimethylformamide) and in the presence of bilirubin and other bile pigments shows that superoxide anion (O2-.) undergoes proton-induced dismutation. Lactam hydrogens of bile pigments are sufficiently acid to induce (O2-.) disproportionation to O2 and H2O2. Because of its characteristic lipophilic behavior, a biological role for natural bilirubin similar to that of other non-enzymatic lipophilic scavengers of (O2-.) is suggested.     

Role of genetic variability in neonatal jaundice. A prospective study on full-term, blood group-compatible infants.

A series of genetic, developmental and environmental variables have been analyzed in a prospective sample of full-term newborn babies, compatible with their mothers in the major blood group systems, in order to attempt an evaluation of the effect of these variables on serum bilirubin level during the first few days of life. Three genetic factors (PGM1, ACP1 and ADA) and three non-genetic variables (rise of bilirubin level during the first day of life, a mother with a history of previous abortion, and use of alcoholic beverages by the mother) have a significant predictive value for the separation of newborns with clinically relevant jaundice from other infants.     

Role of genetic variability in neonatal jaundice. A prospective study on full-term,blood group-compatible infants

A series of genetic, developmental and environmental variables have been analyzed in a prospective sample of full-term newborn babies, compatible with their mothers in the major blood group systems, in order to attempt an evaluation of the effect of these variables on serum bilirubin level during the first few days of life. Three genetic factors (PGM₁, ACP₁ and ADA) and three non-genetic variables (rise of bilirubin level during the first day of life, a mother with a history of previous abortion, and use of alcoholic beverages by the mother) have a significant predictive value for the separation of newborns with clinically relevant jaundice from other infants.     

ABO system incompatibility: evaluation of risk of hyperbilirubinaemia at birth by multivariate discriminant analysis

Summary A discriminant analysis was performed on a set of maternal and neonatal variables to predict at birth the serum bilirubin levels during the neonatal period in infants incompatible with their mothers in the ABO system. The results suggest that the rational and simultaneous utilization of clinical and laboratory parameters allows, a few hours after delivery, a useful classification of these infants in low or high risk for hyperbilirubinemia.This work was supported by grants of NATO, Italian CNR and M.P.I.     

Oxidation of bilirubin with chloranil. A simple method for preparing isomerically pure biliverdin

Summary Isomerically pure biliverdin IXa can be prepared in high yield through dehydrogenation of bilirubin IXa with chloranil-picric acid in chloroform containing t-butanol.     

Influence of dithiocarb on the biliary excretion of paracetamol and bilirubin in rats.

In bile-fistula rats, the biliary elimination of conjugated paracetamol and conjugated bilirubin is diminished by simultaneous administration of dithiocarb. This dithiocarb effect could be the result of the interference with the glucuronidation of the compounds.     

Influence of dithiocarb on the biliary excretion of paracetamol and bilirubin in rats

Summary In bile-fistula rats, the biliary elimination of conjugated paracetamol and conjugated bilirubin is diminished by simultaneous administration of dithiocarb. This dithiocarb effect could be the result of the interference with the glucuronidation of the compounds.     

Inhibition of potassium (86Rb) influx in Ehrlich ascites cells by bilirubin and ouabain

Summary Bilirubin inhibited influx of potassium into Ehrlich ascites cells without altering efflux. The data showed that compared with ouabain, net potassium influx components were impaired in a higher degree by bilirubin. The reversal of this effect was shown, in our experimental conditions, only for ouabain.Acknowledgments. This work was supported by a grant from the Consejo Nacional de Investigaciones Cientificas y Técnicas, República Argentina. The authors wish to thank Miss Marta S. Göthje for techical assistance.     

Solubilization of unconjugated bilirubin by bile salts.

Freshly precipitated unconjugated bilirubin (UCB) is solubilized rapidly and to a large extent by the sodium salts of di- and trihydroxy bile acids. The solubilization effect depending on bile salt concentration, pH and ionic strength is based on micellar mechanisms.     

Solubilization of unconjugated bilirubin by bile salts

Summary Freshly precipitated uncojugated bilirubin (UCB) is solubilized rapidly and to a large extent by the sodium salts of di- and trihydroxy bile acids. The solubilization effect depending on bile salt concentration, pH and ionic strength is based on micellar mechanisms.     

Oxygenation of a dipyrromethene model for bilirubin: formation of a singlet oxygen-like product.

An oxodipyrromethene model compound for bilirubin is found to undergo oxidation to a blue tetrapyrrole and a water-propentdyopent on a silica gel thin layer chromatography plate. The reaction involves ground state oxygen and requires silica gel, although the propentdyopent is an expected product from reaction with singlet oxygen.     

Renal handling of bilirubin photoderivatives

The renal handling of unconjugated bilirubin in the dark and during light exposure was analyzed using an isolated rat kidney preparation. The parameters tested were pigment disappearance from the perfusion medium, pigment uptake by tissue, and its renal clearance. The results indicated that despite the fact that pigment disappearance from the medium was similar for both forms of pigment, the extraction ratio was higher for irradiated pigment than for pigment in the dark. When renal clearance of pigment was plotted vs pigment uptake of tissue, the results indicated that irradiated pigment may be more efficiently removed by the kidney. In addition, data on the rate of secretion of p-aminohippurate suggested that both pigment forms shared a common site for secretion.     

Potential toxins of acute liver failure and their effects on blood-brain barrier permeability

The effects of potentials toxins of hepatic coma on the blood-brain barrier (BBB) permeability of the rat have been examined using the Oldendorf technique. Classical toxins of hepatic failure such as ammonia, methyl octanoate, mercaptans, and phenol caused significant increases in BBB permeability. A slight increase in permeability occurred following infusion of peroxidized linoleic acid and unconjugated bilirubin but no increase after infusion of bile acids. E. coli endotoxin infused into rats following partial hepatectomy also increased the BBB permeability.     

Effect of volatile anesthetics on the circular dichroism of bilirubin bound to human serum albumin.

The characteristic circular dichroism of bilirubin bound to human serum albumin undergoes a remarkable sign inversion on addition of halothane, chloroform and other volatile anesthetics. This sign inversion, which is completely reversed by removal of the anesthetic, reflects a pronounced conformational change of the bound ligand; probably a complete inversion of chirality. The observation suggests that association of volatile anesthetics with proteins can markedly alter the internal topography of receptor sites and potentially influence the stereoselectivity of ligand binding.     

Effect of volatile anesthetics on the circular dichroism of bilirubin bound to human serum albumin

The characteristic circular dichroism of bilirubin bound to human serum albumin undergoes a remarkable sign inversion on addition of halothane, chloroform and other volatile anesthetics. This sign inversion, which is completely reversed by removal of the anesthetic, reflects a pronounced conformational change of the bound ligand; probably a complete inversion of chirality. The observation suggests that association of volatile anesthetics with proteins can markedly alter the internal topography of receptor sites and potentially influence the stereoselectivity of ligand binding.     

Proton-induced dismutation of superoxide in aprotic media by bile pigments

Summary Cyclic voltammetry of molecular oxygen in aprotic media (dimethylformamide) and in the presence of bilirubin and other bile pigments shows that superoxide anion ( ) undergoes proton-induced dismutation. Lactam hydrogens of bile pigments are sufficiently acid to induce disproportionation to O₂ and H₂O₂. Because of its characteristic lipophilic behavior, a biological role for natural bilirubin similar to that of other non-enzymatic lipophilic scavengers of is suggested.     

Oxygenation of a dipyrromethene model for bilirubin: Formation of a singlet oxygen-like product

Summary An oxodipyrromethene model compound for bilirubin is found to undergo oxidation to a blue tetrapyrrole and a water-propentdyopent on a silica gel thin layer chromatography plate. The reaction involves ground state oxygen and requires silica gel, although the propentdyopent is an expected product from reaction with singlet oxygen.The authors wish to thank the National Science Foundation for generous support of this work. We also thank Mr.Richard Gillespie and Ms.Elizabeth Irwin for running the high resolution mass spectra.     

Kinetik der hepatischen Farbstoffaufnahme von Indocyaningrün. Einfluss von Bilirubin und Natriumglykocholat

Summary Kinetics of hepatic uptake of indocyanine green, a dye which is used for evaluation of liver function, were studied in the rat. The results indicate that the relationship between ICG-dose and initial hepatic dye uptake obeys Michaelis-Menten kinetics suggesting an interaction of the dye with a carrier or fixed site in the liver cell. Thus it was possible to calculate maximum ICG-uptake (v _max ) and the Michaelis constant (K _m ) of this transport system from several submaximal values.v _max was 7.65 (6-06-9.65)²² mg per 100 g liver/min and K _m 0.56 (0.31–0.81)²². Under the influence of substances which inhibit the elimination of dyes by the liver the parametersv _max and K _m showed changes which allowed characterization of the type of inhibition. While sodium glycocholate had no influence on maximum hepatic ICG-uptake and the Michaelis constant bilirubin caused a significant increase of K _m to 1.29 (0.68–1.90)²² without significantly changingv _max . These data suggest that bilirubin interferes with hepatic uptake of indocyanine green by competitive inhibition and that uptake of bile acids is dependent on a different mechanism.