Pseudomonas aeruginosa Exotoxin in Mice: Histopathology and Serum Enzyme Changes

Abstract

The histopathology and serum levels of mice inoculated intravenously with Pseudomonas aeruginosa exotoxin were studied. The toxin exerted a marked effect on the liver but elicited no demonstrable microscopic changes in other organs. The microscopic lesions caused in the liver by a single injection of two 50% lethal doses (LD50) of toxin (2.3 mug) were characterized by necrosis, cellular swelling, and fatty change within 4--8 hr and near total hepatocellular necrosis at 48 hr. Hepatic necrosis was accompanied by a parallel rise in serum levels of aspartate and alanine aminotransferases and alkaline phosphatase. A single injection of 10 LD50 elicited similar but somewhat more rapid degeneration. No progressive lesions were seen after injection of toxoid or of 0.5 LD50 of toxin.

Pseudomonas aeruginosa Exotoxin A-Induced Hepatotoxicity: An Animal Model in Rats

“…These findings are similar to the previous observation of PEA-induced hepatotoxicity in mice [16]. Secondly, TUNEL staining appeared to be the earliest feasible indicator detecting hepatotocyte apoptosis.…”

“…In the 30 µg/kg group, mortality was 37% at 48HPE but 25% at 60 HPE, suggesting that the critical hepatotoxicity effect might have saturated by 48 HPE. In comparison with various doses for inducing death in mouse study (85 [20], 300 [4,5], and 500 [15] µg/kg PEA in C57BL/6; 85 [18)] and 300 [26] µg/kg in BALB/c; 115 µg/kg [16] in Swiss; and 600 µg/kg [1] in Mttp ∆/∆ (background: 50% 129/SvJae and 50% C57BL/6)). These were 8-fold differences among the same species animals that appeared to be confusing to researchers.…”

“…This microorganism elaborates varieties of toxic components, such as exotoxin A (PEA), lipopolysaccharide (LPS), phospholipase C, etc. PEA, a 66-kDa protein, is one of the major factors that cause liver damage in experimental animals [10,16,18]. PEA causes inhibition of protein synthesis in mammalian cells via ADP ribosylation of elongation factor 2, a factor that is related to a cellar surface PEA binding protein alpha 2-macroglobulin receptor or low density lipoprotein receptor-related protein 1 (α2MR-LRP1) [11].…”

“…injection have not been convinced. These are wide ranges running from 85 [20,26], 115 [16], 300 [4,5], 500 [15], and 600 µg/kg [1]. As rats are the most common rodent laboratory animals used in hepatotoxicologic assessment, we initiated the study for: 1) Establish a new model using rats for the purpose of liver toxicity investigation, 2) Compare doses in PEA-treated rats with the PEA-treated mice dose for hepatotoxicity study, 3) Detect liver alterations at different doses and time points, and 4) Investigate the possible playing roles of cytokines and immuno-regulators in the PEA-induced hepatotoxicity.…”

Natural history of liver disease in cystic fibrosis

“…Similar to other studies, we found no correlation among liver disease and lung function or bacterial colonization, implying that bacterial toxin production had no great impact on liver damage. 45,46 The prevalence of BLD was surprisingly constant despite changes of treatment modalities during the long study period. The development of more efficient pancreatic enzymes, fat emulsion therapy given more or less regularly, and new intravenous antibiotics directed against P. aeruginosa have improved nutrition and lung function and this might be 1 possible factor behind the low number of patients with severe liver disease despite the increasing median age of our population.…”