Research On The "dose-time-toxicity" Relationship Of Hepatotoxicity And Approach Of The Toxicity Influential Factor Of Pinellia

OBJECTIVE:To research and evaluate the relationshipof dosage-time-toxicity about hepatotoxicity of Pinellia and explore the effect of the inherent characteristics of Traditional Chinese Medicine such as origin, habit, processing, extraction and compatibility on the toxicity of Pinellia in order to provide basement for the caging of toxical meterial and the establishment of relative safety and quality standards in the future.METHODS:Acid-base titration, acid dye colorimetry and HPLC were established to determine the contents of toxicity-related substances in Pinellia. The effects of origin, habit, processing, extraction and compatibility on the toxicity of Pinellia were researched by the classical acute toxicity test method;the same time the "dosage-time-toxicity" relationship about hepatotoxicity of water extraction and toxical enrichment was researched by single administration to mice. Then the level of ALT, AST in serum were tested, and morphous of hepar tissue and ultramicrostructure of hepatic cell were observed with optical microscope or electron microscope.RESULTS:The inherent characteristics of Traditional Chinese Medicine such as origin, habit, processing, extraction and compatibility have an effect on the toxicity and content of related substances and toxicity are related to the contents of total alkaloids and total organic acids. Obvious hepatic injury can be caused to mice by ig water extract of the dosage from 53.1 g·kg-1 to 62.5g·kg-1,or alkaloid enrichment of the dosage from 0.67 g·kg-1 to 1.63g·kg-1;and both the level of ALT, AST in serum reached to the peak at 4h and 2h after administration respectively. The level of ALT, AST in serum increased significantly with the increasing of the dosage.CONCLUSION:Total alkaloids were locked to be the toxical material basement through the genealogical of the effect of the inherent characteristics of Traditional Chinese Medicine such as origin, habit, processing, extraction and compatibility on the toxicity of Pinellia. Single oral administration of water extract and toxical enrichment of certain dosage could cause acute hepatic injury to mice and showed significant "dosage-time-toxicity" relationship. The level of ALT, AST in serum can be regarded as specific and sensitive indicators to test the hepatotoxicity of Pinellia early. The basis for identifying the toxical components of Pinellia and clarifying toxicity targets and mechanism of action were provided,while the foundation was laid for reducing clinical adverse reactions, optimizing production artwork, controlling production quality and guiding safe and rational use of Pinellia in clinical.