Diminished Phosphorylation of CREB Is a Key Event in the Dysregulation of Gluconeogenesis and Glycogenolysis in PCB126 Hepatotoxicity

The dioxin-like PCB126 elicits toxicity in various target organs. In rat liver, an alteration in the transcript levels of several genes involved in glucose and fatty acid metabolism provides insights into the origin of its hepatotoxicity. To explore the mechanisms, male Sprague–Dawley rats, fed an AIN-93G diet, were injected with PCB126 (1 or 5 μmol/kg) or corn oil and euthanized after 2 weeks. PCB126 significantly decreased serum glucose levels and the transcript levels of genes of many gluconeogenic and glycogenolytic enzymes under the transcriptional control of a nuclear transcription factor, cAMP response element-binding protein (CREB). As a novel finding, we show that PCB126 significantly decreases CREB phosphorylation, which is important for regulating both gluconeogenesis and fatty acid oxidation in the liver and explains CREB’s integrative effects on both carbohydrate and lipid metabolism in PCB126 toxicity

Sulfate Conjugates Are Urinary Markers of Inhalation Exposure to 4‑Chlorobiphenyl (PCB3)

PCBs are contaminants in the air of older buildings and cities, which raises the concern of inhalation exposure. No reliable biomarker of such exposure is available. We exposed rats to air containing 2 mg/m³ PCB3 via nose-only inhalation for 2 h, collected urine, and analyzed it by LC/MS. Each rat inhaled an estimated dose of 35 μg PCB3, and excreted 27 ± 2% of it as sulfates within 24 h. Peak excretion occurred within 6 h. PCB sulfates were stable in urine for at least three days at room temperature without chemical preservatives. These data support the use of PCB sulfate conjugates as suitable urinary biomarkers of PCB3 and other airborne PCBs

Inhibition of Human Hepatic and cDNA-Expressed Sulfotransferase Activity with 3-Hydroxybenzopyrene by Polychlorobiphenylols-6

<p><b>Copyright information:</b></p><p>Taken from " Inhibition of Human Hepatic and cDNA-Expressed Sulfotransferase Activity with 3-Hydroxybenzo[]pyrene by Polychlorobiphenylols"</p><p>Environmental Health Perspectives 2005;113(6):680-687.</p><p>Published online 24 Feb 2005</p><p>PMCID:PMC1257591.</p><p>This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original DOI.</p

Inhibition of Human Hepatic and cDNA-Expressed Sulfotransferase Activity with 3-Hydroxybenzopyrene by Polychlorobiphenylols-4

<p><b>Copyright information:</b></p><p>Taken from " Inhibition of Human Hepatic and cDNA-Expressed Sulfotransferase Activity with 3-Hydroxybenzo[]pyrene by Polychlorobiphenylols"</p><p>Environmental Health Perspectives 2005;113(6):680-687.</p><p>Published online 24 Feb 2005</p><p>PMCID:PMC1257591.</p><p>This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original DOI.</p

Inhibition of Human Hepatic and cDNA-Expressed Sulfotransferase Activity with 3-Hydroxybenzopyrene by Polychlorobiphenylols-1

<p><b>Copyright information:</b></p><p>Taken from " Inhibition of Human Hepatic and cDNA-Expressed Sulfotransferase Activity with 3-Hydroxybenzo[]pyrene by Polychlorobiphenylols"</p><p>Environmental Health Perspectives 2005;113(6):680-687.</p><p>Published online 24 Feb 2005</p><p>PMCID:PMC1257591.</p><p>This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original DOI.</p

Inhibition of Human Hepatic and cDNA-Expressed Sulfotransferase Activity with 3-Hydroxybenzopyrene by Polychlorobiphenylols-3

<p><b>Copyright information:</b></p><p>Taken from " Inhibition of Human Hepatic and cDNA-Expressed Sulfotransferase Activity with 3-Hydroxybenzo[]pyrene by Polychlorobiphenylols"</p><p>Environmental Health Perspectives 2005;113(6):680-687.</p><p>Published online 24 Feb 2005</p><p>PMCID:PMC1257591.</p><p>This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original DOI.</p

Inhibition of Human Hepatic and cDNA-Expressed Sulfotransferase Activity with 3-Hydroxybenzopyrene by Polychlorobiphenylols-7

<p><b>Copyright information:</b></p><p>Taken from " Inhibition of Human Hepatic and cDNA-Expressed Sulfotransferase Activity with 3-Hydroxybenzo[]pyrene by Polychlorobiphenylols"</p><p>Environmental Health Perspectives 2005;113(6):680-687.</p><p>Published online 24 Feb 2005</p><p>PMCID:PMC1257591.</p><p>This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original DOI.</p

Tissue Distribution, Metabolism, and Excretion of 3,3′-Dichloro-4′-sulfooxy-biphenyl in the Rat

Polychlorinated biphenyls (PCBs) with less chlorine atoms exhibit a greater susceptibility to metabolism than their more-chlorinated counterparts. Following initial hydroxylation of these less-chlorinated PCBs, metabolic sulfation to form PCB sulfates is increasingly recognized as an important component of their toxicology. Because procedures for the quantitative analysis of PCB sulfates in tissue samples have not been previously available, we have now developed an efficient, LC-ESI-MS/MS-based protocol for the quantitative analysis of 4-PCB 11 sulfate in biological samples. This procedure was used to determine the distribution of 4-PCB 11 sulfate in liver, kidney, lung, and brain as well as its excretion profile following its intravenous administration to male Sprague–Dawley rats. Following initial uptake of 4-PCB 11 sulfate, its concentration in these tissues and serum declined within the first hour following injection. Although biliary secretion was detected, analysis of 24 h collections of urine and feces revealed recovery of less than 4% of the administered 4-PCB 11 sulfate. High-resolution LC-MS analysis of bile, urine, and feces showed metabolic products derived from 4-PCB 11 sulfate. Thus, 4-PCB 11 sulfate at this dose was not directly excreted in the urine but was instead redistributed to tissues and/or subjected to further metabolism

Inhibition of Human Hepatic and cDNA-Expressed Sulfotransferase Activity with 3-Hydroxybenzopyrene by Polychlorobiphenylols-5

<p><b>Copyright information:</b></p><p>Taken from " Inhibition of Human Hepatic and cDNA-Expressed Sulfotransferase Activity with 3-Hydroxybenzo[]pyrene by Polychlorobiphenylols"</p><p>Environmental Health Perspectives 2005;113(6):680-687.</p><p>Published online 24 Feb 2005</p><p>PMCID:PMC1257591.</p><p>This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original DOI.</p

Inhibition of Human Hepatic and cDNA-Expressed Sulfotransferase Activity with 3-Hydroxybenzopyrene by Polychlorobiphenylols-8

<p><b>Copyright information:</b></p><p>Taken from " Inhibition of Human Hepatic and cDNA-Expressed Sulfotransferase Activity with 3-Hydroxybenzo[]pyrene by Polychlorobiphenylols"</p><p>Environmental Health Perspectives 2005;113(6):680-687.</p><p>Published online 24 Feb 2005</p><p>PMCID:PMC1257591.</p><p>This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original DOI.</p