Influence of Age on Susceptibility to Pseudomonas aeruginosa Exotoxin A-induced Hepatotoxicity in Long-Evans Rats(Pathology)
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概要
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Epidemiological investigations suggest that increased age is associated with susceptibility to infection. Pseudomonas aeruginosa (P. aeruginosa) infection and associated exotoxin A (PEA) toxicity have been reported in hospitalized elderly patients and young children with cystic fibrosis. The present study investigated age-related differences in PEA-induced hepatotoxicity in post weaning (PW, 3 weeks), young adult (YA, 12 weeks), and mature adult (MA, 60-64 weeks) rats. PEA (20μg/kg) was injected intraveneously and mortality, clinical chemistry, hepatic histopathology, TUNEL (Terminal deoxynucleotidyl transferase-mediated dUTP nick end-labelling) and PCNA (Proliferating cell nuclear antigen) staining, and serum cytokine levels were assessed at specific time points, up to 72hr post-exposure (HPE). Mortality in MA rats was 100% at less than 48 HPE. Serum ALT levels in MA rats were approximately 5-fold greater than levels in PW and YA rats at 36 HPE. MA rat liver histological sections showed diffuse hepatocellular necrosis. In contrast, hepatocellular apoptosis, demonstrable by the TUNEL method, was noted simply in the periportal and midzonal regions from 36 to 48 HPE. Increased morphological mitoses and PCNA-positive hepatocytes were seen in PW and YA rats at 72 HPE. These parameters were correlated with age-dependent significant increases in TNF-α, IL-2, IL-6, and IL-18 levels. These data suggest that inflammatory cytokines play an important role in age-related differences in PEA-induced hepatotoxicity. Moreover, these cytokines might correlate with different patterns histopathologic features at various ages.
- 社団法人日本獣医学会の論文
- 2009-02-25
著者
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Chung Tung-ching
Department Of Veterinary Medicine National Chung Hsing University
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Chiu Chien-chao
Department Of Veterinary Medicine National Chung Hsing University
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Chen Hans
Hans Chen Biotechpath Consulting Ltd.
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CHUANG Hsiao-Li
Department of Veterinary Medicine, National Chung Hsing University
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HUANG Yen-Te
National Laboratory Animal Center, National Applied Research Laboratories
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CHEN Hans
Yushu BiotechPath Consulting, Ltd.
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CHU Ying-Yueh
Department of Food, Health and Nutrition Science, Chinese Culture University
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CHEN Ter-Hsin
Institute of Veterinary Public Health, National Chung Hsing University
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Chu Ying-yueh
Department Of Food Health And Nutrition Science Chinese Culture University
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Huang Yen-te
Research & Development Division National Laboratory Animal Center National Applied Research Labo
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- Influence of Age on Susceptibility to Pseudomonas aeruginosa Exotoxin A-induced Hepatotoxicity in Long-Evans Rats(Pathology)