Inhibitory Effect of Tetrachloro‐<i>p</i>‐Hydroquinone and Other Metabolites of Hexachlorobenzene on Hepatic Uroporphyrinogen Decarboxylase Activity with Reference to the Role of Glutathionea

Koss, G.; Losekam, M.; Seidel, Jutta; Steinbach, K; Koransky, W.

doi:10.1111/j.1749-6632.1987.tb48769.x

Cited by 12 publications

(3 citation statements)

References 43 publications

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“…Hepatic GSH content in rats was found to be decreased by 50% within 24 h following oral administration of HCB (200 mg/kg) (Ingebrigtsen et al, 1981). A dose-dependent depletion of GSH in HCB exposed rats was found in another study (Koss et al, 1987). Our results were in agreement with these works.…”

Section: Gsh and Gsh-related Enzymes In Brainsupporting

confidence: 91%

Effects of hexachlorobenzene on antioxidant status of liver and brain of common carp (Cyprinus carpio)

2006

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Section: Gsh and Gsh-related Enzymes In Brainsupporting

confidence: 91%

Effects of hexachlorobenzene on antioxidant status of liver and brain of common carp (Cyprinus carpio)

2006

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“…It is feasible that reactive oxygen species such as peroxides and free radicals (cf Ferioli et al 1984) are increasingly formed and that with advancing age of the animals their detoxication declines. The consequence could be glutathione depletion followed by a functional impairment of the uroporphyrinogen decarboxylase activity (Koss et al 1987). Further investigations into the reasons for the observed exceptional delayed onset of porphyria in the PCB 180 pretreated animals are therefore indispensable.…”

Section: Discussionmentioning

confidence: 99%

2,2′,3′,4,4′,5,5′-Heptachlorobiphenyl (PCB 180) — on its toxicokinetics, biotransformation and porphyrinogenic action in female rats

et al. 1993

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The toxicokinetics and biotransformation of 2,2',3',4,4',5,5'-heptachlorobiphenyl, as well as its influence on the activity of microsomal and cytosolic enzymes and on the porphyrin pathway in the liver were studied in female rats following oral treatment with 7 mg/kg every other day for 3 months. One day after cessation of treatment the concentration of the compound in liver, spleen, CNS and blood was 100-500 times and in the trachea it was only 5 times less than in the adipose tissue. The daily excretion with the feces and urine amounted to 35 and 1.5 micrograms, respectively. In both excreta, heptachlorobiphenylol was identified as a metabolite. The biotransformation rate was estimated to be about 5%. Investigations of the liver revealed increases in the relative liver weight, total cytochrome P-450 content, O-deethylation of 7-ethoxycoumarin and in the activity of glutathione S-transferases. Disturbances of the hepatic porphyrin pathway were not detected. Only at the end of a post-dosing period of 12 months did the hepatic uroporphyrinogen decarboxylase show diminished activity. Only one of these animals with diminished enzyme activity showed drastically elevated porphyrins. In these animals, the fecal and urinary porphyrins did not differ from controls. At no time did heptachlorobiphenyl influence the urinary excretion of delta-aminolevulinic acid and porphobilinogen. The results indicate 1) that this congener shows expected toxicokinetics with the exception of being accumulated in the trachea and 2) that this congener induces disturbances of the hepatic porphyrin pathway several months after cessation of treatment.

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“…The above finding represents an unusual pathway for alkoxyl/ketoxy radical and/or HNE production not involving redox-active metals and may explain, at least in part, the potential carcinogenicity of not only PCP but also other widely used halogenated aromatic carcinogens (hexachlorobenzene, Agent Orange, and brominated flame-retardants) since these chemicals can be metabolized in vivo − ,− or oxidized to tetra-, di-, or mono-XQ. Our findings showed that XQ may interact with ROOH and cause deleterious effects via facilitated generation of alkoxyl/ketoxy radicals and/or HNE and hence elevated damage to macromolecules.…”

Section: Conclusion and Future Researchmentioning

confidence: 88%

Molecular Mechanism of Metal-Independent Decomposition of Organic Hydroperoxides by Halogenated Quinoid Carcinogens and the Potential Biological Implications

Huang

Ren

Shan

et al. 2015

Chem. Res. Toxicol.

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Halogenated quinones (XQ) are a class of carcinogenic intermediates and newly identified chlorination disinfection byproducts in drinking water. Organic hydroperoxides (ROOH) can be produced both by free radical reactions and enzymatic oxidation of polyunsaturated fatty acids. ROOH have been shown to decompose to alkoxyl radicals via catalysis by transition metal ions, which may initiate lipid peroxidation or transform further to the reactive aldehydes. However, it is not clear whether XQ react with ROOH in a similar manner to generate alkoxyl radicals metal-independently. By complementary applications of ESR spin-trapping, HPLC/high resolution mass spectrometric and other analytical methods, we found that 2,5-dichloro-1,4-benzoquinone (DCBQ) could significantly enhance the decomposition of a model ROOH tert-butylhydroperoxide, resulting in the formation of t-butoxyl radicals independent of transition metals. On the basis of the above findings, we detected and identified, for the first time, an unprecedented C-centered quinone ketoxy radical. Then, we extended our study to the more physiologically relevant endogenous ROOH 13-hydroperoxy-9,11-octadecadienoic acid and found that DCBQ could also markedly enhance its decomposition to generate the reactive lipid alkyl radicals and the genotoxic 4-hydroxy-2-nonenal (HNE). Similar results were observed with other XQ. In summary, these findings demonstrated that XQ can facilitate ROOH decomposition to produce reactive alkoxyl, quinone ketoxy, lipid alkyl radicals, and genotoxic HNE via a novel metal-independent mechanism, which may explain partly their potential genotoxicity and carcinogenicity.■ CONTENTS

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Inhibitory Effect of Tetrachloro‐p‐Hydroquinone and Other Metabolites of Hexachlorobenzene on Hepatic Uroporphyrinogen Decarboxylase Activity with Reference to the Role of Glutathionea

Cited by 12 publications

References 43 publications

Effects of hexachlorobenzene on antioxidant status of liver and brain of common carp (Cyprinus carpio)

Effects of hexachlorobenzene on antioxidant status of liver and brain of common carp (Cyprinus carpio)

2,2′,3′,4,4′,5,5′-Heptachlorobiphenyl (PCB 180) — on its toxicokinetics, biotransformation and porphyrinogenic action in female rats

Molecular Mechanism of Metal-Independent Decomposition of Organic Hydroperoxides by Halogenated Quinoid Carcinogens and the Potential Biological Implications

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