Differences in Genetic Background Contribute to Pseudomonas Exotoxin A-Induced Hepatotoxicity in Rats
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 s...
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MDPI AG
2017-07-01
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| Series: | Toxins |
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| Online Access: | https://www.mdpi.com/2072-6651/9/7/224 |
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| author | Chien-Chao Chiu Yu-Chih Wang Wen-Ching Huang Yi-Hsun Chen Shao-Wen Hung Yen-Te Huang Hsiao-Li Chuang Yi-Chih Chang |
| author_facet | Chien-Chao Chiu Yu-Chih Wang Wen-Ching Huang Yi-Hsun Chen Shao-Wen Hung Yen-Te Huang Hsiao-Li Chuang Yi-Chih Chang |
| author_sort | Chien-Chao Chiu |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-11T18:43:41Z |
| format | Article |
| id | doaj.art-005041af23f44bfb8d20d03c7e4e579b |
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| issn | 2072-6651 |
| language | English |
| last_indexed | 2024-04-11T18:43:41Z |
| publishDate | 2017-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Toxins |
| spelling | doaj.art-005041af23f44bfb8d20d03c7e4e579b2022-12-22T04:08:53ZengMDPI AGToxins2072-66512017-07-019722410.3390/toxins9070224toxins9070224Differences in Genetic Background Contribute to Pseudomonas Exotoxin A-Induced Hepatotoxicity in RatsChien-Chao Chiu0Yu-Chih Wang1Wen-Ching Huang2Yi-Hsun Chen3Shao-Wen Hung4Yen-Te Huang5Hsiao-Li Chuang6Yi-Chih Chang7Animal Technology Laboratories, Agricultural Technology Research Institute, Miaoli 350, TaiwanGraduate Institute of Veterinary Pathobiology, College of Veterinary Medicine, National Chung Hsing University, Taichung 402, TaiwanDepartment of Exercise and Health Science, National Taipei University of Nursing and Health Sciences, Taipei 112, TaiwanGraduate Institute of Veterinary Pathobiology, College of Veterinary Medicine, National Chung Hsing University, Taichung 402, TaiwanAnimal Technology Laboratories, Agricultural Technology Research Institute, Miaoli 350, TaiwanNational Laboratory Animal Center, National Applied Research Laboratories, Taipei 115, TaiwanNational Laboratory Animal Center, National Applied Research Laboratories, Taipei 115, TaiwanDepartment of Medical Laboratory Science and Biotechnology, China Medical University, Taichung 404, TaiwanPseudomonas 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.https://www.mdpi.com/2072-6651/9/7/224Pseudomonas exotoxin Agenetic backgroundhepatotoxicitymassive necrosis |
| spellingShingle | Chien-Chao Chiu Yu-Chih Wang Wen-Ching Huang Yi-Hsun Chen Shao-Wen Hung Yen-Te Huang Hsiao-Li Chuang Yi-Chih Chang Differences in Genetic Background Contribute to Pseudomonas Exotoxin A-Induced Hepatotoxicity in Rats Toxins Pseudomonas exotoxin A genetic background hepatotoxicity massive necrosis |
| title | Differences in Genetic Background Contribute to Pseudomonas Exotoxin A-Induced Hepatotoxicity in Rats |
| title_full | Differences in Genetic Background Contribute to Pseudomonas Exotoxin A-Induced Hepatotoxicity in Rats |
| title_fullStr | Differences in Genetic Background Contribute to Pseudomonas Exotoxin A-Induced Hepatotoxicity in Rats |
| title_full_unstemmed | Differences in Genetic Background Contribute to Pseudomonas Exotoxin A-Induced Hepatotoxicity in Rats |
| title_short | Differences in Genetic Background Contribute to Pseudomonas Exotoxin A-Induced Hepatotoxicity in Rats |
| title_sort | differences in genetic background contribute to pseudomonas exotoxin a induced hepatotoxicity in rats |
| topic | Pseudomonas exotoxin A genetic background hepatotoxicity massive necrosis |
| url | https://www.mdpi.com/2072-6651/9/7/224 |
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