Induction of Oxidative Stress in the Tissues of Rats After Chronic Exposure to Tcdd, 2,3,4,7,8-Pentachlorodibenzofuran, and 3,3',4,4',5-Pentachlorobiphenyl

Abstract

The abilities of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), 2,3,4,7,8-pentachlorodibenzofuran (PeCDF), 3,3',4,4',5-pentachlorobiphenyl (PCB126), and mixtures of these xenobiotics (toxic equivalents, TEQs) to induce oxidative stress in hepatic and brain tissues of rats have been investigated after chronic (30 wk) exposure to these congeners. TCDD, PeCDF, PCB126, and TEQs were administered daily to groups of rats at doses that corresponded to their toxic equivalency factors (TEFs), and the biomarkers of oxidative stress, including the production of superoxide anion, lipid peroxidation, and DNA single-strand breaks (SSBs), were determined in hepatic and brain tissues at the end of the exposure period. The three chemicals caused similar dose-dependent increases in the production of superoxide anion, lipid peroxidation, and DNA SSBs, which plateaued at certain dose ranges, followed by secondary increases at the higher dose levels. Similar effects were also produced by the TEQs; however, the dose-dependent increases in the biomarkers of oxidative stress were continuous and never achieved plateau levels. Except for PCB126, where statistical analyses revealed greater productions of superoxide anion and lipid peroxidation in brain tissues as compared with hepatic tissues, no significant differences were revealed between the two tissues in response to the other xenobiotics or the TEQs. Nonsignificant differences were also revealed when comparing the effects induced by the TEQs with those induced by the individual chemicals.

Oral administration of PCBs induces proinflammatory and prometastatic responses

“…It was demonstrated that PCB77 can uncouple the catalytic cycle of CYP1A1, allowing heme iron within the active site of this enzyme complex to act as a Fenton catalyst and generating hydroxyl radicals from hydrogen peroxide (Schlezinger et al, 1999;Schlezinger et al, 2006). Other coplanar PCBs, such as PCB126 and PCB169 also markedly increased cellular oxidative stress in vascular endothelial cells, brain, and hepatic tissues (Twaroski et al, 2001;Hassoun et al, 2002;Ramadass et al, 2003) with superoxide anions being a major reactive oxygen species. Thus, induction of CYP1A1 or CYP1A2 may lead to generation of excess levels of reactive oxygen species, resulting in cell injury.…”

For Dioxin-induced Birth Defects, Mouse or Human CYP1A2 in Maternal Liver Protects whereas Mouse CYP1A1 and CYP1B1 Are Inconsequential

“…Several reports have shown that TCDD produces oxidative stress (55)(56)(57)(58). Low dose TCDD causes a sustained oxidative stress in liver that is dependent on the AHR but independent of the presence of CYP1A1 or CYP1A2 (49, 59, 60).…”

Dioxin-mediated tumor progression through activation of mitochondria-to-nucleus stress signaling

“…Wasting (cachexia), thymic involution, tumor promotion, hepatotoxicity, developmental toxicity, and immunosuppression are a few of the pathological effects of TCDD (14,15). TCDD is also known to induce oxidative stress, production of superoxide and peroxide radicals, and DNA singlestrand breaks (16)(17)(18). However, the cellular and molecular mechanisms of TCDD-mediated pathologies are poorly understood.…”

“…TCDD and related dioxins are well established ligands for aryl hydrocarbon receptor (AhR), which modulates transcriptional activation of many genes, including those involved in fatty acid metabolism (18), cell cycle regulation, immune response, and xenobiotic metabolism. Binding of TCDD to AhR triggers AhR nuclear translocation and its heterodimerization with AhR nuclear translocator (Arnt).…”