Pseudomonas aeruginosa exotoxin A (PEA) causes severe hepatotoxicity in experimental\nanimals and is useful in investigations of immune-mediated liver injury. However, strain differences\nin the sensitivity to PEA-induced hepatotoxicity in rats remains be elucidated. In this study, we\ndetermined the severity of PEA-induced hepatotoxicity in six genetically different rat strains. Male LE\n(Long Evans), Wistar, F344, WKY, BN/SsN and LEW rats were administered a single intravenous\ninjection of PEA (20 �¼g/kg). Significantly elevated serum ALT and AST levels, massive necrosis and\nhemorrhage, and numerous TUNEL-positive hepatocytes were observed in BN/SsN rats. In contrast,\nlow levels of ALT and AST as well as mild changes in liver histopathology were observed in\nWistar and F344 rats. Moderate levels of hepatic injuries were observed in LE, WKY, and LEW rats.\nPro-inflammatory cytokines including TNF-�±, IL-2 and IL-6 serum levels were markedly increased in\nBN/SsN rats compared toWistar and F344 rats. However, the hepatic levels of low density lipoprotein\nreceptor-related protein (LRP), which functions as the PEA receptor, were not significantly different in\neach strain. Taken together, we suggest that BN/SsN is the most sensitive rat strain, whereas Wistar\nand F344 were the most resistant rat strains to PEA-induced liver damage. The different genetic\nbackground of rat strains plays an important role in the susceptibility to PEA-induced epatotoxicity\nthat may depend on immune-regulation but not LRP receptor levels.
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