Aim: This study was designed to study the toxicity of LHRH-PE40, a recombinant DNA-derived protein composed of the decapeptide known as luteinizing hormone-releasing hormone and the translocation and catalytic domains of pseudomonas exotoxin A.
Method: Single-dose and repeat-dose toxicity of intravenous injection of LHRH-PE40 was studied by clinical signs, hematology, blood chemistry and histopathology, and lung permeability to Evans blue dye. Additional study was performed to find the relationship between dexamethasone pretreatment and vascular leak syndromes.
Results: Dyspnea, increased hemocrit, low serum total protein, lung edema, and high lung permeability were found on rats treated with single or repeated doses of LHRH-PE40. Dexamethasone pretreatment before LHRH-PE40 administration partly lowered morbidity of rats.
Conclusion: LHRH-PE40-induced vascular leak syndrome was the chief cause of rats' death. Dexamethasone pretreatment partly reduced the frequency of vascular leak syndrome. Hypotheses about vascular leak syndromes were also formed by reviewing recent literature.