Role of bilirubin as a natural antioxidant in regulation of the intensity of lipid peroxidation in acute virus hepatitis

Blyuger, A. F.; Dudnik, L. B.; Maiore, A. Ya.; Mieze, I. É.

doi:10.1007/bf00798666

Cited by 18 publications

(16 citation statements)

References 4 publications

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“…Some earlier and neglected work has also suggested that bilirubin might play a role as an antioxidant (9)(10)(11). Indeed, reactions of bilirubin involving free radicals (12,13) or toxic oxygen reduction products are well documented in the literature: unconjugated bilirubin scavenges singlet oxygen with high efficiency (14), reacts with superoxide anion (15) and peroxyl radicals (7), and serves as a reducing substrate for peroxidases in the presence of hydrogen peroxide or organic hydroperoxides (16,17).…”

mentioning

confidence: 99%

Potential role of conjugated bilirubin and copper in the metabolism of lipid peroxides in bile.

Stocker

Ames

1987

Proc. Natl. Acad. Sci. U.S.A.

126

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Conjugated bilirubin and copper ions at their physiological concentrations in bile may play an important role in hydroperoxide and other detoxification. Conjugated bilirubin may also be an important chain-breaking antioxidant preventing lipid peroxidation. Bilirubin ditaurine (BR-DT), a water-soluble model compound of conjugated bilirubin, completely prevents the peroxyl radical-induced oxidation of phosphatidylcholine in either multilamellar liposomes or micelles. This antioxidant activity is associated with the bilirubin moiety of BR-DT, since taurine alone is inefficient in scavenging peroxyl radicals. The number of peroxyl radicals trapped per molecule of BR-DT is 1.9, compared to 4.7 trapped per molecule of biliverdin, the water-soluble physiological precursor of bilirubin. Peroxyl radical-induced oxidation of BR-DT results in a spectral shift in maximal absorbance toward shorter wavelengths; biliverdin is not formed as a major oxidation product. BR-DT, but neither taurine nor biliverdin, greatly accelerates the cupric ion-catalyzed decomposition of linoleic acid hydroperoxide. In the presence of ferric ion, BR-DT shows no lipid hydroperoxide-degrading activity. Addition of cupric ion to BR-DT results in formation of a complex with spectral features similar to that of a biliverdin-cupric ion complex, indicating that BR-DT and cupric ion undergo redox reactions.

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mentioning

confidence: 99%

Potential role of conjugated bilirubin and copper in the metabolism of lipid peroxides in bile.

Stocker

Ames

1987

Proc. Natl. Acad. Sci. U.S.A.

126

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“…Moreover, DOC metabolites produced by cytochrome P450 act as detergents and destruct substrate-binding site in the enzyme, which considerably impairs its interaction with substrates and reduces its catalytic activity. Impaired hydroxylation of cholesterol backbone results in accumulation of cytotoxic mono-and dihydroxy bile acid derivatives in hepatocytes [2,4,10]. Their high concentrations or prolonged exposure produces a detergent effect on hepatocyte endoplasmic reticulum membranes resulting in uncoupling of membrane enzyme complexes, conversion of cytochrome P450 into inactive cytochrome P420 and destruction of substratebinding centers in the enzyme molecule.…”

Section: Resultsmentioning

confidence: 99%

“…Binding of DOC to cytochrome P450 (type I bond) and oxidation by this enzyme determine its competition with other substrates for binding sites on this hemoprotein, oooo oo decreased metabolism of many xenobiotics [2]. Moreover, DOC metabolites produced by cytochrome P450 act as detergents and destruct substrate-binding site in the enzyme, which considerably impairs its interaction with substrates and reduces its catalytic activity.…”

Section: Resultsmentioning

confidence: 99%

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Dysfunction and correction of microsomal enzyme oxidation, glucuronidation and glutathione conjugation of xenobiotics in the liver of deoxycholate-intoxicated rats

Bushma¹,

Legon'kova²,

Zverinskii³

et al. 2000

Bull Exp Biol Med

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Intoxication with deoxycholic acid is accompanied by destruction of hepatocyte plasma membrane (increased serum alanine aminotransferase activity) and inhibition of monooxygenase, glucuronidase and glutathione systems of rat liver. Heptral and cordiamine (mitethamide) had no effect on membrane integrity, while a-tocopherol and ursofalk (ursodeoxycholic acid) protected membranes. Ursofalk and cordiamine are superior a ~-tocopherol and heptral by their ability to activity of monooxygenase, glucuronidase, and glutathione conjugating systems in the liver.

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“…DCA binds to type I cytochrome P450 binding sites and is oxidized by the enzyme, thus competing with other substrates, which decreases metabolism of many xenobiotics [2]. Furthermore, cytochrome P450 induces the formation of DCA hydroxyderivatives, which possess detergent properties and destroy substratebinding sites in the enzyme molecule.…”

Section: Resultsmentioning

confidence: 99%

Correction of dysfunction of enzyme systems of microsomal oxidation, glucuronidation, and glutathione conjugation of xenobiotics in the liver of rats with deoxycholate intoxication

et al. 2000

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Intoxication with deoxycholic acid disturbed the integrity of hepatocyte plasma membranes (elevation of alanine transaminase activity in the plasma) and inhibited the monooxygenase, glucuronosyltransferase, and glutathione S-transferase systems in rat liver. Heptral and cordiaminum did not affect the integrity of plasma membranes, while ~-tocopherol and, especially, ursofalk produced membrane-protective effects. Ursofalk and, especially, cordiaminum are far superior to (~-tocopherol and heptral in their ability to normalize functions of the monooxygenase, glucuronosyltransferase, and glutathione S-transferase systems in rat liver. Key Words: deoxycholic acid-induced liver damage; biotransformation of xenobiotics: heptral; cordiaminum; ursofalk: o~-tocopherolThe blood of animals and humans with cholestasis contains considerable amounts of cholates, other bile components, and intermediate products of impaired metabolism and. therefore, is toxic to the body. Endotoxemia m cholestasis leads to liver dysfunction and impairs biotransformation of drugs and other xenobiotics. This promotes their accumulation in the body and aggravates intoxication. Experiments on animals showed that hydrophobic fatty acids play the major role in the pathogenesis of hepatotoxicity during cholestasis [ 12].Here we studied disturbances in xenobiotic transformation in the liver during deoxycholic acid (DCA) intoxication. Heptral. (~-tocopherol, ursofalk, and cordiaminum were used to correct metabolic dysfunction. MATERIALS AND METHODSExperiments were performed on 62 male rats weighing 200-240 g. DCA was administered through a gastric tube (i.g., 250 mg/kg/day in starch slurry) for 8 days. Heptral (100 mg/kg), cordiaminum (50 mg/kg), and vitamin E (50 mg/kg) were injected intraperitoneally (i.p.); ursofalk was administered i.g. (100 mg/kg/day in the starch slurry). Control rats received equivalent amounts of DCA or starch slurry (i.g.) and 0.85% NaC1 (i.p.). Twenty-four hours after the last injection. the animals were decapitated and liver microsomal fractions were isolated. The concentration of proteins and the content of cytochromes b s and P450 were measured. The rates of NADPH and NADH oxidation, aminopyrine demethylation, and aniline p-hydroxylation and activities of NADPH-cytochrome P450 and NADH-cytochrome b 5 oxidoreductases, uridine 5'-diphosphoglucuronyl transferase (UDP-glucuronosyltransferase), glutathione S-transferase, and uridine-5'-diphosphoglucose dehydrogenase (UDP-glucose dehydrogenase) were estimated by the method described elsewhere [3]. The urinary excretion of glucuronic acid [14] and activity of alanine transaminase (ALT) in the serum [5] were estimated. RESULTS

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Role of bilirubin as a natural antioxidant in regulation of the intensity of lipid peroxidation in acute virus hepatitis

Cited by 18 publications

References 4 publications

Potential role of conjugated bilirubin and copper in the metabolism of lipid peroxides in bile.

Potential role of conjugated bilirubin and copper in the metabolism of lipid peroxides in bile.

Dysfunction and correction of microsomal enzyme oxidation, glucuronidation and glutathione conjugation of xenobiotics in the liver of deoxycholate-intoxicated rats

Correction of dysfunction of enzyme systems of microsomal oxidation, glucuronidation, and glutathione conjugation of xenobiotics in the liver of rats with deoxycholate intoxication

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