Long-term effects of subcutaneously injected 2,3,7,8-tetrachlorodibenzo-p-dioxin on the liver of rhesus monkeys

Autor: Toshio Fukusato, Shunichiro Kubota, Mari Ohta, Akihiro Arima, Kazuo Asaoka, Tatsumi Korenaga, Nobuo Murata
Rok vydání: 2007
Předmět:
medicine.medical_specialty
Polychlorinated Dibenzodioxins
Time Factors
Environmental Engineering
Injections
Subcutaneous
Health
Toxicology and Mutagenesis
Hemorrhage
Biology
Downregulation and upregulation
Antigens
CD
Pregnancy
Transforming Growth Factor beta
Internal medicine
Cytochrome P-450 CYP1A1
medicine
Animals
Environmental Chemistry
heterocyclic compounds
Cadherin
Liver Diseases
Public Health
Environmental and Occupational Health
Endothelial Cells
Muscle
Smooth
Thrombosis
General Medicine
General Chemistry
Transforming growth factor beta
Hyperplasia
Blotting
Northern
Cadherins
medicine.disease
Aryl hydrocarbon receptor
Macaca mulatta
Pollution
Fatty Liver
Endothelial stem cell
Microscopy
Electron
medicine.anatomical_structure
Endocrinology
Receptors
Aryl Hydrocarbon
Infarction
Hepatocyte
biology.protein
Female
Chemical and Drug Induced Liver Injury
VE-cadherin
Zdroj: Chemosphere. 67:S399-S404
ISSN: 0045-6535
Popis: 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) accumulates and remains stable in the fatty tissues and liver of rodents for a long time. Considering the pronounced difference between species, long-term, low dose hepatic effects of TCDD were investigated after subcutaneous administration of TCDD into rhesus monkeys during pregnancy. Macroscopic and histopathological examination of the liver carried out 4 y after TCDD administration demonstrated intrahepatic focal fatty changes, infarction, hemorrhage, microthrombi-formation, sinusoidal ectasia, small hepatocyte hyperplasia, and increased number of alpha-smooth muscle actin (alpha-SMA)-positive cells. An electron microscopic study disclosed sinusoidal endothelial cell degeneration and injury in the liver of TCDD-treated monkeys. Western blot analysis showed downregulation of aryl hydrocarbon receptor (AhR) protein expression and decreased level of vascular endothelial (VE) cadherin but increased expression levels of CYP1A1 and transforming growth factor beta (TGF-beta) protein in the liver tissues. These changes observed in TCDD-exposed monkeys indicated sinusoidal endothelial cell injury and impairment in intrasinusoidal microcirculation. Infarction, focal fatty change, and microthrombi-formation are considered to be closely associated with intrahepatic circulatory impairment. Increased number of alpha-SMA-positive cells and decreased level of VE cadherin expression in the liver tissues might also be associated with sinusoidal endothelial cell injury. In addition, downregulation of AhR expression and increased CYP1A1 protein levels in the liver were consistent with persistent effects of TCDD. Although it has been reported that TCDD induced endothelial cell injury, this is the first report to describe vascular disorders and protein expression in the liver after injection with TCDD in a primate model.
Databáze: OpenAIRE
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