Comparative study on chronic multiple organ injury in normal rats caused by high dose of Tripterygium Glycosides Tablets from 6 different manufacturers / 中国中药杂志

The aim of this paper was to compare different effects of Tripterygium Glycosides Tablets from 6 different manufacturers on multiple organ injuries in rats and to explore mechanism of hepatotoxicity preliminarily from the perspective of apoptosis and oxidative stress. Rats were randomly divided into the groups normal, Zhejiang, Hunan, Hubei, Shanghai, Jiangsu and Fujian(7 groups with 16 rats in each group, sex in half). Rats were given Tripterygium Glycosides Tablets at 144 mg·kg~(-1)·d~(-1)(16 times the clinical equivalent dose) once a day according to its corresponding group like rats in Zhejiang group was given Tripterygium Glycosides Tablets from Zhejiang manufactures continuously for 20 days with the life and death situation of mice to be observed, then rats were executed to detect various indicators. RESULTS:: showed that 8 female rats in Zhejiang group died after 15 days of administration, the serum NEUT of rats in Hubei, Fujian and Shanghai groups was significantly lower than that of normal rats. The serum AST, ALT and/or TBiL levels were increased in all rats, and serum BUN and/or CRE levels of rats were also increased in Hunan, Hubei, Fujian and Shanghai groups. In dosage groups, testicular and ovarian coefficients of rats were reduced, the number of sperm were significant decreased while the rate of sperm malformation increased and sperm dynamics parameters of normal, especially in Jiangsu and Zhejiang groups. Liver histopathology and apoptosis of liver cells were observed in dosage groups, especially in Jiangsu and Hubei groups. In liver, Nrf2, HO-1 and Bcl-2 were inhibited and the protein expression level of Bax were increased simultaneously in dosage groups. These results showed that all Tripterygium Glycosides Tablets from 6 manufacturers could lead to chronic multiple organ injuries with disparate specialties in rats, and Jiangsu and Zhejiang groups were more toxic. It could be the mechanism promoting mitochondrial mediated Bax/Bcl-2 cell apoptosis signaling pathway and negatively regulating Nrf2/HO-1 oxidative stress signaling pathway that Tripterygium Glycosides Tablets from 6 different manufacturers resulted in chronic liver injury, the results above were for reference only in subsequent study.

Effects of Tripterygium Glycosides Tablets from 6 different manufacturers on acute liver injury of normal mice / 中国中药杂志

The aim of this paper was to compare the performance of acute liver injury in mice induced by Tripterygium Glycosides Tablets from 6 different manufacturers,and to explore the toxicity mechanism from the perspective of oxidative stress and apoptosis preliminarily. Male or female mice were randomly divided into normal group,Zhejiang group,Hunan group,Hubei group,Shanghai group,Jiangsu group and Fujian group. Mice in Tripgerygium Glycosides Tablets groups were given 16 times the clinical equivalent dose( 300 mg·kg-1) Tripgerygium Glycosides Tablets by oral administration for one time,mice were executed in 24 h after lavaged.Then the visceral brain coefficient of the organ was calculated. Histopathological changes of liver were observed by hematoxylin-eosin staining. Td T-mediated d UTP nick-end labeling was used to detect the apoptosis of the liver cells and the protein content of oxidative stress related factors in liver homogenate. Nuclear transcription factor E2-related factor( Nrf2) and heme oxygenase-1( HO-1) as well as mitochondrial mediated apoptosis-related protein expression levels of Bax and Bcl-2 in hepatic tissue were measured by Western blot.Within 24 hours of administration,6 male mice in Jiangsu group and 2 female mice in Zhejiang group were dying; compared with normal ones,liver coefficients of mice in Zhejiang,Shanghai,Jiangsu and Hunan groups were significantly increased,thymus coefficients in the first two groups were significantly reduced,as well as the lung coefficients of Fujian group mice,the rest was normal. In addition to Hubei group,serum AST,ALT or ALP levels of mice were increased,while TBi L were not being affected. Histopathological changes and apoptosis of liver cells were observed in all mice,and the degree of severity was ranked as Jiangsu,Zhejiang,Shanghai,Hunan,Hubei and Fujian group. All Tripterygium Glycosides Tablets increased the MDA and reduced the content of T-SOD,CAT or GSH in liver tissue while inhibited Nrf2,HO-1 and Bcl-2,increased the protein expression level of Bax( except Hunan group). Tripgerygium Glycosides Tablets from 6 manufacturers all resulted in liver function damage and liver histopathological changes,especially in Jiangsu,Hubei and Fujian,and the mechanism may related to inhibit Nrf2/HO-1 oxidative stress pathway and activate Bax/Bcl-2 apoptosis pathway to mediate lipid peroxidation and induce liver cell apoptosis. Triptolide A may be one of the main toxic components of Tripgerygium Glycosides Tablets that causing drug-induced liver injury. This study was conducted on normal mice with super dose medication,so the relevant results are for reference only.