Research On "Dose-Time-Toxicity" Relationship Of Hepatotoxicity Caused By Volatile Oil From Bupleurum Chinense

Objective:To research and evaluate the"dose-time-toxicity"relationship of hepartotoxicity caused by volatile oil from Bupleurum Chinense in order to provide basis for the elucidation of the hepatotoxical mechanism of volatile oil from Bupleurum Chinense and revelation of scientific connotation of"Bupleurum Chinense robbing hepatic yin"as well as establish foundation for the quality control of Bupleurum Chinense and its preparation,optimization of manufacture technology and the safe application of preparation containing of volatile oil from Bupleurum Chinense.Methods:The extract technology of volatile oil from Bupleurum Chinense was screened with the guidance of toxicity and its acute toxicity of intragastric administration in rats and mice was researched by the classical acute toxicity test method; the research on"dose-time-toxicity"relationship of acute and chronic hepatotoxicity caused by single or multiple intragastric administration to mice or rats were carried on,and then the level of ALT, AST in serum were tested, and macropathological and pathohistological changes were observed with optical microscope or electron microscope.The hepatotoxical mechanism of volatile oil from Bupleurum Chinense was studied preliminary.Results: The volatile oil from Bupleurum Chinense extracted by the method from Pharmacopeia is optimal to the systematic research of its toxicity.Obvious acute toxicity can be caused to rats and mice by single intragastric administration of volatile oil from Bupleurum Chinense,the LD₅₀ and its 95% confident limit are 2.081(1.760～2.461)mL·kg^-1 and 3.118 ( 2.872～3.391 ) mL·kg^-1 differently.1h after the intragastric administration of 0.624 mL·kg^-1 volatile oil to mice, both the level of ALT and AST in serum reached to the peak and 12h after ig. pathological changes were obvious.The hepatotoxicty increased with the increase of dosage in the range of (0.383～0.624) mL·kg^-1.Multiple intragastric administration of essential oil from Bupleurum Chinense with dosage from 0.19mL·kg^-1 to 0.42mL·kg^-1 for 30days may induce chronic hepatotoxical injury in rats the level of ALT, AST in serum and hepar index increased significantly after 7d and the toxical expression reach to extreme from 15d to 21d after administration.The oxidation resistance reduced and the free radicals accumulated after the intragastric administration of essential oil from Bupleurum Chinense for 15 days.Conclusion: The intragastric administration of volatile oil from Bupleurum Chinense can cause fairly strong acute toxicity to rats and mice.Chronic or acute hepatotoxical injury can be induced by multiple or single intragastric administration of volatile oil from Bupleurum Chinense with certain dosage and the level of ALT,AST in serum have a most obvious change.The change showed significant"dose-time-toxicity"relationship in a certain range.Peroxidation injury is one of the main hepatotoxical mechanism.The research can provide experimental basis for the elucidation of target and mechanism of hepatotoxicty and establish foundation for the quality control of Bupleurum Chinense,optimization of manufacture technology and the safe application of preparation containing of volatile oil from Bupleurum Chinense.