Analysis of vascular endothelial growth factor (VEGF) and a receptor subtype (KDR/flk-1) in the liver of rats exposed to riddelliine: a potential role in the development of hemangiosarcoma

Experimental and Toxicologic Pathology : Official Journal of the Gesellschaft Für Toxikologische Pathologie
C MoyerA Nyska

Abstract

Riddelliine alters hepatocellular and endothelial cell kinetics and function including stimulating an increase in hepatocytic vascular endothelial growth factor (VEGF) in the absence of increased serological levels of VEGF (NYSKA et al. 2002). The objective of this study was to further assess hepatic VEGF and KDR/flk-1 synthesis and expression by hepatic cells under riddelliine treatment conditions. Forty-two male F344/N rats were dosed by gavage with riddelliine (0, 1.0, and 2.5 mg/kg/day) for 6 weeks. Seven animals/group were sacrificed after 8 consecutive daily doses; remaining rats were terminated after 30 daily doses, excluding weekends. Hepatic tissues were evaluated by immunohistochemistry and in situ hybridization. The results showed that VEGF mRNA expression was observed in control and treated animals; however, qualitative differences were noted. Treated animals exhibited VEGF mRNA in clustered, focal hepatocytes and bile duct epithelium, whereas VEGF mRNA in hepatocytes from vehicle control rats was distributed evenly across all hepatocytes. Results evaluating the distribution of the VEGF cognate receptor, KDR/flk-1 showed that randomly distributed, rare sinusoidal endothelium, including those demonstrating karyomegal...Continue Reading

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Jun 16, 2009·Toxicological Sciences : an Official Journal of the Society of Toxicology·Samuel M CohenJon C Cook
May 18, 2010·International Journal of Cancer. Journal International Du Cancer·Shuang WangKai-Tai Yao
Nov 9, 2010·Critical Reviews in Oncology/hematology·Nicolas PenelPeter Hohenberger
Jul 31, 2007·Experimental Gerontology·Rajkumar CheluvappaDavid G Le Couteur
Feb 6, 2008·Experimental and Toxicologic Pathology : Official Journal of the Gesellschaft Für Toxikologische Pathologie·Li-Li JiZheng-Tao Wang
Jun 2, 2007·Hepatology Research : the Official Journal of the Japan Society of Hepatology·Ze-Sheng WangHui Li
Sep 26, 2013·Journal of Personality Assessment·Lena C QuiltyR Michael Bagby

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