RESUMO
Objective:To investigate the pharmaceutical idiosyncratic hepatotoxicity effect of Xanthii Fructus on the immune-sensitive rat model induced by endotoxin lipopolysaccharide （LPS）. Method:The SD rats were randomly divided into five groups： control group， model group， and three Xanthii Fructucs groups. The immune-sensitive rat model was established by LPS （iv. 0.7 mg·kg-1， twice every 7 days）. Then， the rats in control and model groups received the equal volume of distilled water， while the rats in Xanthii Fructus groups were administrated with water extract of Xanthii Fructus intragastrically （1.67， 5.01， 16.7 g·kg-1， respectively） for 14 days. The serum and liver of the rats were collected on the 7th and 14th day to examine the levels of hepatotoxic biomarkers， including alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， total bilirubin （TBil）， alkaline phosphatase （ALP）， and total bile acids （TBA）， and liver histopathology. In addition， inflammatory factors， including interleukin-1β（IL-1β）， interleukin-2（IL-2）， interleukin-6（IL-6）， interleukin-10（IL-10）and tumor necrosis factor-α（TNF-α）of the idiosyncratic hepatotoxicity rats， were determined by enzyme-linked immunosorbent assay（ELISA）. Result:The immune-sensitive model rats showed elevated levels of IL-1β， IL-6（P<0.05，P<0.01）， and mild inflammatory cells infiltrated in portal area of liver significantly （P<0.05）， with no significant changes in hepatotoxic biomarkers. Meanwhile， there was no significant change between Xanthii Fructus groups and model rats in the levels of hepatotoxic biomarkers， inflammatory factors and hepatic lesions. Conclusion:Water extract of Xanthii Fructus intragastrically does not affect the levels of hepatotoxic biomarkers， inflammatory factors and hepatic lesions in rats induced by LPS intravenously. That is to say， Xanthii Fructus does not induce pharmaceutical idiosyncratic hepatotoxicity.
RESUMO
This study was designed to investigate the correlation between idiosyncratic liver injury and content of cis-2,3,5,4'-tetrahydroxystilbene-2-O-β-D-glucoside(cis-SG)in radix Polygoni multiflori Preparata(RPMP). In order to compare the effect of hepatotoxicity of different cis-SG contents in RPMP, rats were administered with 50% alcohol extracts of RPMP(7.56 g·kg-1, via intragastric administration)alone or co-treated with lipopolysaccharide(LPS, 2.8 mg·kg-1, via tail vein injection). The results showed that no significant alterations of plasma ALT and AST activities were observed in the normal rats. In the LPS treated rats, the group without light treatment and the group with 0.10% cis-SG after light treatment did not exhibit obvious injury in liver. The group with 0.35% cis-SG after light treatment and the group with 0.70% cis-SG after light treatment showed significant increases in ALT, AST, TNF-α, IL-6, NF-κB p65 and apoptosis rate(P < 0.05), causing pathological changes in the liver tissue. Through the content analysis of drug in patients with liver injury, we found that the content of cis-SG(> 0.40%)was generally higher than that of pieces collected from different origins(< 0.10%). The comparative analysis of experiments and clinical data showed that there was a relationship between the content of cis-SG and idiosyncratic liver injury. In order to reduce the risk of clinical medication, the content of cis-SG of 0.10% should be a limit of quality control in the production processing of Polygonum multiflorum.