Induction of hepatic portal fibrosis, mitochondria damage, and extracellular vesicle formation in Sprague-Dawley rats exposed to copper, manganese, and mercury, alone and in combination
Autor: | Megan Jean Bester, Chantelle Venter, Priyanka Dhanraj, Hester Magdalena Oberholzer |
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Rok vydání: | 2020 |
Předmět: |
0301 basic medicine
Male medicine.medical_specialty Portal triad medicine.disease_cause Pathology and Forensic Medicine Rats Sprague-Dawley 03 medical and health sciences 0302 clinical medicine Microscopy Electron Transmission Structural Biology Fibrosis Internal medicine medicine Animals chemistry.chemical_classification Reactive oxygen species Manganese Environmental exposure Extracellular vesicle Mercury medicine.disease Mitochondria Rats 030104 developmental biology Endocrinology medicine.anatomical_structure chemistry 030220 oncology & carcinogenesis Hepatocyte Toxicity Hepatocytes Chemical and Drug Induced Liver Injury Oxidative stress Copper |
Zdroj: | Ultrastructural pathology. 44(2) |
ISSN: | 1521-0758 |
Popis: | Increased anthropogenic activity and subsequent environmental exposure to heavy metals induce the production of reactive oxygen species (ROS), which increases oxidative stress and the risk of associated diseases. The aim of this study, in a subacute model of toxicity, was to investigate the effects of copper (Cu), manganese (Mn), and mercury (Hg) alone and in combination on the liver tissue of male Sprague-Dawley rats, exposed orally to 100 times the World Health Organization's acceptable water limits of each metal. General histological alterations as well as ultrastructural changes were investigated using light microscopy and transmission electron microscopy (TEM) respectively. Exposure to Cu, Mn, and Hg, alone and in combinations, caused hydropic swelling of the hepatocytes, dilation of the sinusoids, formation of binucleated hepatocytes with an increased inflammatory cell accumulation at the portal triad. Increased collagen deposition with associated fibrosis was also observed. Evaluation of hepatocyte ultrastructure revealed mitochondrial membrane damage and inner membrane swelling especially for hepatocytes exposed to Mn. Extracellular vesicle (EV) formation was observed in the liver tissue of all exposed rats. Furthermore, increased damage observed for metal combinations was possibly due to synergism. In conclusion, Cu, Mn, and Hg alone and as part of a mixture cause cellular damage, inflammation, and fibrosis increasing the risk of associated diseases. |
Databáze: | OpenAIRE |
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