Short-term toxicity of aristolochic acids Ⅰ in C57BL/6 and C3H/He mice
Objective To compared the tolerance and toxicity of different strains of mice to aristolochic acid Ⅰ(AAⅠ)to provide a reference and guidance for the study of AAⅠ.Methods C57BL/6 and C3H/He mice were treated with AAⅠ by oral gavage.Each strain of mice was assigned one vehicle control and seven AAⅠ dose(5.0,9.3,17.1,31.7,58.6,108.4,and 200.5 mg·kg-1)groups,and clinical symptom observation and weight measurement were performed after dosing.At the end of the experiment,necropsy,organ weighing,serum biochemical index detection,and pathological examination were performed.Results A single administration of a certain dose of AAⅠ caused weight loss,emaciated,arched back,reduced activity,and even death in both strains of mice,and the dosage of AAⅠ in C57BL/6 mice with the above changes was lower than that in C3H/He mice.The AAⅠ median lethal dose(LD50)of C57BL/6 mice was 38.07 mg·kg-1,and that of C3H/He mice was 59.92 mg·kg-1.The maximum tolerated dose(MTD)of AAⅠ in C57BL/6 mice was 17.1 mg·kg-1,and that in C3H/He mice was 31.7 mg·kg-1.AAⅠ did not induce serum biochemical changes in C57BL/6 mice,while increased levels of ALT,AST,and CRE were found in C3H/He mice.AAⅠ can cause acute injury to multiple organs in C57BL/6 and C3H/He mice,such as the thymus,spleen,kidneys,liver,and forestomach.And the dose of AAⅠ causing histopathological changes in the the above-mentioned tissues and organs of C3H/He mice was lower than that of C57BL/6 mice.Conclusion By analyzing the overall toxicity,serum biochemical indicators,causes of animal death,and histopathological changes caused by different doses of AAⅠ in C57BL/6 and C3H/He mice,it was concluded that C3H/He mice were more sensitive to acute toxicity of AAⅠ than C57BL/6 mice.This study not only verified the acute toxicity characteristics and target organs of AAⅠ on C57BL/6 and C3H/He mice,but also provided rich data support for comparing the sensitivity and tolerance of different strains of mice to AAⅠ acute toxicity,and provided detailed reference data for more scientific and reasonable research on AAⅠ in the future.
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