Constitutive and aroclor 1254-induced hepatic glutathione S-transferase, peroxidase and reductase activities in genetically inbred mice

Makary, Moheb H.; Kim, H.L.; Safe, Stephen; Womack, James E.; Ivie, G. Wayne

doi:10.1016/0742-8413(88)90054-0

Cited by 8 publications

(3 citation statements)

References 34 publications

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“…The slight increase of GSSG and decrease of GSH or total glutathione in PCBexposed liver, if any, were minor compared to the enormous amount of intrahepatic glutathione. Similar findings showing no change in hepatic GSH/GSSG level were reported after intraperitoneal injection of Aroclor 1254 or individual congeners 16,38 except PCB 126 at a high dose of 326 μg/ kg. 17 observed in general, blood GSSG-to-GSH ratio provides an index of intracellular redox status.…”

Section: ■ Discussionsupporting

confidence: 83%

Subchronic Inhalation Exposure Study of an Airborne Polychlorinated Biphenyl Mixture Resembling the Chicago Ambient Air Congener Profile

Adamcakova‐Dodd

Lehmler

et al. 2012

Environ. Sci. Technol.

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Although inhalation of atmospheric PCBs is the most universal exposure route and has become a substantial concern in urban areas, research is lacking to determine the body burden of inhaled PCBs and consequent health effects. To reflect the Chicago airshed environment and mimic the PCB profile in Chicago air, we generated vapors from a Chicago Air Mixture (CAM). Sprague-Dawley rats were exposed to the CAM vapor for 1.6 hr/day via nose-only inhalation for 4 wks, 520±10 μg/m3. Congener-specific quantification in tissue and air samples was performed by GC/MS/MS. In contrast to the lower-chlorinated congener enriched vapor, body tissues mainly contained tri- to hexachlorobiphenyls. Congener profiles varied between vapor and tissues, and among different organs. The toxic equivalence (TEQ) and neurotoxic equivalence (NEQ) were also investigated for tissue distribution. We evaluated a variety of endpoints to catalog the effects of long-term inhalation exposure, including immune responses, enzyme induction, cellular toxicity and histopathologic abnormalities. GSSG/GSH ratio was increased in blood of exposed animals, accompanied by elevation of hematocrit. This study demonstrated that inhalation contributed to the body burden of mostly tri- to hexachlorobiphenyls and produced a distinct profile of congeners in tissue, yet minimal toxicity was found at this exposure dose estimated at 134 μg/rat.

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Section: ■ Discussionsupporting

confidence: 83%

Subchronic Inhalation Exposure Study of an Airborne Polychlorinated Biphenyl Mixture Resembling the Chicago Ambient Air Congener Profile

Adamcakova‐Dodd

Lehmler

et al. 2012

Environ. Sci. Technol.

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“…The slight increase of GSSG and decrease of GSH or total glutathione in PCB-exposed liver, if any, were minor compared to the enormous amount of intrahepatic glutathione. Similar findings showing no change in hepatic GSH/GSSG level were reported after intraperitoneal injection of Aroclor 1254 or individual congeners (Makary et al 1988;Twaroski et al 2001) except PCB126 at a high dose of 326 μg/kg (Lai et al 2010). Although there were minimal toxicity-related effects observed in general, blood GSSG-to-GSH ratio provides an index of intracellular redox status.…”

Section: Discussionsupporting

confidence: 76%

Distribution, elimination and toxicity assessment of semi-volatile polychlorobiphenyls after inhalation exposure

Hu¹

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Inhalation exposure to semi-volatile polychlorobiphenyls (PCBs) that ubiquitously exist in the environment has the potential to cause adverse health effects. Recently identified sources of airborne PCBs, especially non-legacy sources, stress the importance of risk assessment for inhalation exposure. However, the fate of inhaled airborne PCBs in biological systems and the resultant toxicity remain unexplored. The objective of this thesis research was to investigate the distribution and elimination of semi-volatile PCBs in biological systems after inhalation exposure and evaluate the biologic and toxicologic consequences. This objective was achieved by conducting the following inhalation studies in rats: a short-term exposure study of the body burden and elimination; a subchronic exposure toxicity study; an acute exposure study of PCB11 metabolism; and a mass balance study of [ 14 C]PCB11 following lung exposure. PCBs found in technical Aroclor mixtures and PCB11 were readily absorbed and distributed following nose-only inhalation exposure. PCBs accumulated in adipose tissue, but decayed in other tissues with biological half-lives of several hours. Their elimination was dependent on the structure of the PCB congeners and the metabolic nature of the organ. Lower-chlorinated PCBs exhibited more rapid clearance than higher-chlorinated congeners yet differential rates of elimination were also seen within the homologue. A distinct congener pattern was found in tissues, ranging from tri-to pentachorobiphenyls after subacute and subchronic exposure. Rapid elimination of PCB11 and its metabolite, 4-OH-CB11, were detected in liver following nose-only inhalation exposure by our established methodology. Further investigation revealed that [ 14 C]PCB11 was 99.8% absorbed in lung. Elimination of the [ 14 C]PCB11 and products consisted of an initial fast phase followed by a slow clearance phase.

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“…Our results also indicate small differences with CDNB (Table 3.17) after sporidesmin dosing, with the dosed resistant animals apparently showing a small increase in activity 1.14 times greater than the dosed susceptible animals. A similar result was obtained by Makary et al (1988) after Aroclor 1254 administration to geneticalfy inbred mice. They found that Aroclor 12i4-treatment caused a 4.2 told induction of GST in NFS/NCR mice, but only a 1.4 fold increase in AKR/NCR mice.…”

Section: Electrophoresis and Western Blottinq Of Microsomal Proteinssupporting

confidence: 83%

Molecular Markers For Selection of Resistance to Facial Eczema

Kuhait¹

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<p>The disease facial eczema is caused by the fungal metabolite sporidesmin which produces photosensitisation of animals whose liver and biliary tract have been damaged by the toxin. Sporidesmin is produced by the pasture fungus Pithomyces chartarum and affects ruminant animals that graze on contaminated pasture. Previous studies have shown that sporidesmin is metabolised in the liver and have suggested that the toxin is metabolically inactivated by enzymes in the glutathione S-transferase and cytochrome P-450 families. The activities of these enzymes were therefore measured in liver extracts from Romneys that had been selected for resistance or susceptibility to sporidesmin - induced liver damage. Although there were no differences in cytochrome P-450 CO binding spectra or cytochrome c reductase between the selection lines, resistant Romneys had greater nitroanisole O-demethylase activity and this difference was apparently enhanced two days after dosing with sporidesmin. Dose-dependent differences occurred in the absence of major hepatocellular injury suggesting that they reflected changes in enzyme activity rather than changes in tissue mass. Aminopyrine N-demethylase did not vary significantly between the selection lines. Some differences in GSH-dependent metabolism were also observed. Undosed resistant Romneys showed greater GSH-dependent metabolism of sporidesmin in a spectrophotometric assay. It is possible that glutathione S-transferase Mu or Theta isoforms had greater activity in the resistant lines as differences were observed using p-nitrobenzyl chloride and 1,2 epoxy-3-p-nitrophenoxypropanol but not with 1-chloro-2,4-dinitrobenzene or 1,2-dichloro-4-nitrobenzene that are good substrates for these isoforms. 2-D PAGE was applied to the separation of whole homogenate and soluble proteins. Variations in expression of some proteins including GST Mu isoforms were found between the selection lines. Roles of cytochrome P-450 and glutathione S-transferase in the hepatic detoxication of sporidesmin have previously been demonstrated. Results obtained in this study suggest that resistant Romneys may have greater cytochrome P-450 O-demethylase and glutathione S-transferase activities that could be responsible for increased metabolic inactivation of sporidesmin. These differences may in the future be of use in design of DNA probes to enhance detection and selection of facial eczema resistant livestock.</p>

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Constitutive and aroclor 1254-induced hepatic glutathione S-transferase, peroxidase and reductase activities in genetically inbred mice

Cited by 8 publications

References 34 publications

Subchronic Inhalation Exposure Study of an Airborne Polychlorinated Biphenyl Mixture Resembling the Chicago Ambient Air Congener Profile

Subchronic Inhalation Exposure Study of an Airborne Polychlorinated Biphenyl Mixture Resembling the Chicago Ambient Air Congener Profile

Distribution, elimination and toxicity assessment of semi-volatile polychlorobiphenyls after inhalation exposure

Molecular Markers For Selection of Resistance to Facial Eczema

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