Effect of in vivo administered hexachlorobenzene on epidermal growth factor receptor levels, protein tyrosine kinase activity, and phosphotyrosine content in rat liver

Randi, Andrea; Sancovich, H. A.; Sancovich, A M Ferramola de; Loaiza, Andrea; Frers, Rodolfo A. Kölliker; Spinelli, Fernanda; Pisarev, Diana L. Kleiman de

doi:10.1016/s0006-2952(03)00107-2

Cited by 10 publications

(3 citation statements)

References 40 publications

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“…In utero exposure to HCB did not consistently affect the body weights of rats across their 100 days of life 64. Similarly, adult female rats exposed to HCB did not experience a change in body mass after 1 month 65,66. Mice prenatally exposed to 100 mg DDT/kg maternal body weight/day had higher body weights in the week after birth when the study ended 67.…”

Section: Candidate Obesogensmentioning

confidence: 86%

Childhood Obesity and Environmental Chemicals

Merrill

Birnbaum

2011

Mount Sinai J Medicine

152

113

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Childhood and adolescent rates of obesity and overweight are continuing to increase in much of the world. Risk factors such as diet composition, excess caloric intake, decreased exercise, genetics, and the built environment are active areas of etiologic research. The obesogen hypothesis, which postulates that prenatal and perinatal chemical exposure can contribute to risk of childhood and adolescent obesity, remains relatively underexamined. This review surveys numerous classes of chemicals for which this hypothesis has been explored. We focus on human data where they exist and also discuss the findings of rodent and cell culture studies. Organochlorine chemicals as well as several

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Section: Candidate Obesogensmentioning

confidence: 86%

Childhood Obesity and Environmental Chemicals

Merrill

Birnbaum

2011

Mount Sinai J Medicine

152

113

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“…When active, EGFR stimulates proproliferative signaling (Seshacharyulu et al, 2013). In HCB feeding studies, this herbicide has already demonstrated to increase microsomal EGFR content and activation in rat liver (Randi et al, 2003(Randi et al, , 2008. Here, all HCB-promoted groups showed strong cytoplasmic TGF-a immunostaining.…”

Section: Discussionmentioning

confidence: 66%

Vitamin D3 supplementation attenuates the early stage of mouse hepatocarcinogenesis promoted by hexachlorobenzene fungicide

Romualdo

Goto

Fernandes

et al. 2017

Food and Chemical Toxicology

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Hexachlorobezene (HCB), a fungicide widely distributed in the environment, promotes the development of hepatocellular preneoplastic lesions (PNL) and tumors in rodents. In contrast, vitamin D (VD) supplementation presents a potential role for the prevention/treatment of chronic liver diseases. Thus, we investigated whether VD supplementation attenuates the early stage of HCB-promoted hepatocarcinogenesis. Female Balb/C mice were injected a single dose of diethylnitrosamine (DEN, 50 mg/kg) at postnatal day 15. From day 40 onwards, mice were fed with a standard diet containing 0.02% HCB alone or supplemented with VD (10,000 or 20,000 IU/Kg diet) for 20 weeks. Untreated mice were fed just standard diet. After this period, mice were euthanized and liver and serum samples were collected. Compared to the untreated group, DEN/HCB treatment decreased total hepatic glutathione levels and glutathione peroxidase (GSH-Px) activity while increased lipid peroxidation, p65 protein expression, cell proliferation/apoptosis and the PNL development. In contrast, dietary VD supplementation enhanced vitamin D receptor (VDR) protein expression, total glutathione levels and GSH-Px activity while diminished lipid hydroperoxide levels. Also, VD supplementation decreased p65 protein expression, hepatocyte proliferation, the size and the liver area occupied by PNL. Therefore, our findings indicate that VD supplementation attenuates the early stage of HCB-promoted hepatocarcinogenesis.

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“…Control (N) animals received equal volumes of the appropiate solvent by the same route. The dose of HCB employed was chosen based on previous studies from our laboratory and those of other researchers (Kleiman de Pisarev, Ferramola de Sancovich, and Sancovich 1995;van Raaij et al 1993;Fernández Tomé et al 2000;Randi et al 1998Randi et al , 2003Loaiza Pérez et al 1999), demonstrating that this dose elicited clear manifestations of hepatic porphyria and thyroid hormone metabolism alterations. The general health of the animals was not affected by the dose of HCB employed, as it was evaluated by the behavior and appearance of the rats, including examination of their coats, mucous membranes, and body weights, and their food and water consumption.…”

Section: Animalsmentioning

confidence: 99%

Hexachlorobenzene Treatment on Hepatic Mitochondrial Function Parameters and Intracellular Coproporphyrinogen Oxidase Location

Sopena

Sancovich

2008

Int J Toxicol

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These studies try to elucidate why isocoproporphyrin appears in hexachlorobenzene-poisoned rats' feces. Chronic exposure of hexachlorobenzene to rats produces an experimental model for human porphyria cutanea tarda. After 8 weeks of treatment, rats showed high porphyrin excreta and 50% inhibition of liver uroporphyrinogen decarboxylase activity. Uroporphyrin plus heptacarboxylic porphyrin exceeded coproporphyrin in urine, whereas in feces, isocoproporphyrin, from abnormal pentacarboxylic porphyrinogen III oxidative decarboxylation by liver coproporphyrinogen oxidase, became the main porphyrin. Trypsin-treated mitochondria showed that the outer and inner membrane permeability barrier was highly conserved after hexachlorobenzene intoxication. In digitonin-treated hexachlorobenzene mitochondria, coproporphyrinogen oxidase was free in the mitochondrial intermembrane space, whereas in normal mitochondria, 30% to 50% remained anchored to the inner membrane. Hexachlorobenzene led to a decrease in respiratory control and ADP/O ratios (uncoupled mitochondria). Albumin restored oxidative phosphorylation, indicating no irreversible inner membrane damage. Normal and hexachlorobenzene mitochondria oscillatory studies exhibited similar damping factor values, showing that hexachlorobenzene had no significant effect on membrane fluidity and elasticity. Mitochondrial uncoupling could explain the free state of the enzyme within the intermembrane space. The free state of the enzyme makes it more flexible and would allow pentacarboxylic porphyrinogen III, whose levels are increased, to compete with coproporphyrinogen III and being transformed into dehydroisocoproporphyrinogen, the liver forerunner of fecal isocoproporphyrin.

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Effect of in vivo administered hexachlorobenzene on epidermal growth factor receptor levels, protein tyrosine kinase activity, and phosphotyrosine content in rat liver

Cited by 10 publications

References 40 publications

Childhood Obesity and Environmental Chemicals

Childhood Obesity and Environmental Chemicals

Vitamin D3 supplementation attenuates the early stage of mouse hepatocarcinogenesis promoted by hexachlorobenzene fungicide

Hexachlorobenzene Treatment on Hepatic Mitochondrial Function Parameters and Intracellular Coproporphyrinogen Oxidase Location

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