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Ecotoxicology and Environmental Safety 2018-Oct

Differential susceptibility of kidneys and livers to proliferative processes and transcriptional level of the genes encoding desmin, vimentin, connexin 43, and nestin in rats exposed to furan.

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Ashraf Awad
Samah R Khalil
Mayada Ragab Farag
Mohamed Abdo Nassan

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概要

In this study, we aimed to assess the differential toxic impact, induced by furan exposure, on the liver and kidney tissues by estimating reactive oxygen species (ROS) level, total antioxidant capacity (TAC), oxidative damage, and the tissue injury markers in a male rat model. To explain such impacts, 20 rats were assigned into two groups: a control group, where rats were administered corn oil as a vehicle, and a furan-administered group, where furan was orally administered to rats at a dose of 16 mg/kg b wt/day (five days per week over eight weeks). The transcriptional levels of intermediate filament proteins (desmin, vimentin, nestin, and connexin 43) were assessed by using quantitative real-time polymerase chain reaction (PCR), and the cell proliferation markers (proliferating cell nuclear antigen [PCNA] and proliferation-associated nuclear antigen [Ki-67]) were recognized by immunohistochemical analysis. Furthermore, the ultrastructural changes of liver and kidney were monitored using electron microscopy. Our findings showed that furan exposure could induce hepatic and renal damage to different extents. Furan can increase the ROS content, oxidative damage indices, and liver tissue injury indices but not kidney injury indices. Furthermore, it decreases the TAC in the serum of exposed rats. In addition, furan exposure was associated with changes in the mRNA expression pattern of intermediate filament proteins in both kidney and liver tissues. Moreover, furan enhances the expression of PCNA and Ki-67 in the liver tissues but not in the kidney tissues. The ultrastructure evaluation revealed the incidence of glomerular podocyte degeneration and hepatocyte injury. These results conclusively demonstrate that the deleterious effects of furan are caused by promoting fibrosis and hepatocyte proliferation in liver tissues and triggering podocyte injury in the kidney tissues.

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