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Toxins 2017, 9(7), 224;

Differences in Genetic Background Contribute to Pseudomonas Exotoxin A-Induced Hepatotoxicity in Rats

Animal Technology Laboratories, Agricultural Technology Research Institute, Miaoli 350, Taiwan
Graduate Institute of Veterinary Pathobiology, College of Veterinary Medicine, National Chung Hsing University, Taichung 402, Taiwan
Department of Exercise and Health Science, National Taipei University of Nursing and Health Sciences, Taipei 112, Taiwan
National Laboratory Animal Center, National Applied Research Laboratories, Taipei 115, Taiwan
Department of Medical Laboratory Science and Biotechnology, China Medical University, Taichung 404, Taiwan
These authors contributed same to this work.
Author to whom correspondence should be addressed.
Academic Editor: Vernon L. Tesh
Received: 17 May 2017 / Revised: 13 July 2017 / Accepted: 13 July 2017 / Published: 15 July 2017
(This article belongs to the Section Bacterial Toxins)
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Pseudomonas aeruginosa exotoxin A (PEA) causes severe hepatotoxicity in experimental animals and is useful in investigations of immune-mediated liver injury. However, strain differences in the sensitivity to PEA-induced hepatotoxicity in rats remains be elucidated. In this study, we determined the severity of PEA-induced hepatotoxicity in six genetically different rat strains. Male LE (Long Evans), Wistar, F344, WKY, BN/SsN and LEW rats were administered a single intravenous injection of PEA (20 μg/kg). Significantly elevated serum ALT and AST levels, massive necrosis and hemorrhage, and numerous TUNEL-positive hepatocytes were observed in BN/SsN rats. In contrast, low levels of ALT and AST as well as mild changes in liver histopathology were observed in Wistar and F344 rats. Moderate levels of hepatic injuries were observed in LE, WKY, and LEW rats. Pro-inflammatory cytokines including TNF-α, IL-2 and IL-6 serum levels were markedly increased in BN/SsN rats compared to Wistar and F344 rats. However, the hepatic levels of low density lipoprotein receptor-related protein (LRP), which functions as the PEA receptor, were not significantly different in each strain. Taken together, we suggest that BN/SsN is the most sensitive rat strain, whereas Wistar and F344 were the most resistant rat strains to PEA-induced liver damage. The different genetic background of rat strains plays an important role in the susceptibility to PEA-induced epatotoxicity that may depend on immune-regulation but not LRP receptor levels. View Full-Text
Keywords: Pseudomonas exotoxin A; genetic background; hepatotoxicity; massive necrosis Pseudomonas exotoxin A; genetic background; hepatotoxicity; massive necrosis

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Chiu, C.-C.; Wang, Y.-C.; Huang, W.-C.; Chen, Y.-H.; Hung, S.-W.; Huang, Y.-T.; Chuang, H.-L.; Chang, Y.-C. Differences in Genetic Background Contribute to Pseudomonas Exotoxin A-Induced Hepatotoxicity in Rats. Toxins 2017, 9, 224.

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