Effects of Jiedu hugan granule on the inflammatory factor and tight junction protein of small intestine in rats with immunological liver injury / 中国临床药理学与治疗学

AIM:To investigate the influence of Jiedu hugan granule on the inflammatory factor and tight junction protein of small intestine in rats with immunological liver injury.METHODS:Fifty SD rats were randomly divided into control group,model group,low,middle and high experimental group of Jiedu hugan granule (2.7,5.4,and 10.8 g/kg).All the groups excepted the control group received intraperitoneal injections of 0.5 mL pig serum for each to establish immunological liver injury model.The experimental group was irrigated ltime/d,continuous dosing for 14 d.The liver tissue and small intestinal tissue pathological changes were observed by HE staining,the serum alanine aminotransferase (ALT),aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) were detected,and the expression of liver tissue TNF-α and small intestine tissue occludin-5 were detected by immunohistochemical method.RESULTS:The model group liver tissue showed accumulation of fat cells,liver cells enlargement,disorganized liver and associated with inflammatory cells infiltration;the experimental group liver cell morphological ruled,hepatic cords in alignment and inflammatory cells infiltration significantly decrease.The model group small intestinal mucosa villi showed atrophy,fall off of epithelial cell,edema,large number of inflammatory cells infiltration;the experimental group showed closelyknitted small intestinal mucosa villi,relieve edema,and no obvious infiltration of inflammatory cells.The levels of ALT,AST,LDH and TNF-α in experimental group were statistically lower than the model group,and the levels were statistically reduce with the dose of jiedu hugan granule increased.The levels of occludin-5 in experimental group were statistically highter than those of the model group,and the levels of occludin-5 were statistically increase with the dose of Jiedu hugan granule increased,the differences were statistically significant (P ＜ 0.05).CONCLUSION:Jiedu hugan granule can improve the organizational structure of liver and small intestine,protect the damage of liver,reduce inflammation,and maintain small intestine mucosal barrier function.

Reduction of Total Antioxidant Capacity in Artemether-treated Female Schistosoma japonicum / 中国寄生虫学与寄生虫病杂志

Objective To study the effect of artemether (Art) on total antioxidant capacity (T-AOC) in adult Schistosoma japonicum. Methods In vitro, the T-AOC was determined in five-week old worms incubated without or with Art and/or hemin for 24 h, and the worms were continuously incubated for 96 h, then worm survival was assessed. In vivo, T-AOC was determined in worms freshly recovered from mice 6 - 24 h after treatment with Art 300 mg/kg. Results Throughout 96 h incubation no worms were killed by 50 μmol/L Art or 50 μmol/L hemin alone, but approximatdy 80% of them were killed by Art plus hemin. Addition of reduced glutathione and vitamin E could significantly block the cidal action of the combined treatment. No effect on T-AOC was seen in the worms exposed to Art or heroin alone for 24 h, but the combined treatment led to a pronounced T-AOC reduction in female worms in vitro. Such a drug effect on female worms was demonstrated in vivo. After female worms were exposed to Art for 6 - 24 h in vivo, their T-AOC was significantly reduced by 40% - 64%. However, no drug effect on male worms' T-AOC was observed in vivo and in vitro exposed to Art plus hemin. Conclusion Art-induced T-AOC reduction in female worms may sensitize them to lethal damages of endogenous and exogenous oxygen radicals.

EFFECT OF PRAZIQUANTEL DERIVATIVE S83143 AND ITS SALTS ON INFECTION OF SCHISTOSOMA JAPONICUM IN MICE / 中国药理学通报

Effect of S83143, a praziquantel derivative, and its phosphate salt S85009, sulfate salt S85010 and hydrochloride salt S85021 on different developmental stages of Schistosoma japonicum in mice were ob- served. When infected mice were treated with S83143 suspension at a single oral dose of 400 mg/kg or with 3 different salts of S83143 at a single intramuscular dose of 100 mg' ( S83143 base )/kg, the worm reduction rate was 69~87% in 2 h old schistosomula and 47~96% in 32~33 d old adult worms, respectively, but had no effect on 3 ~14 d schistosomula. The results showed that the susceptibility of different developmental stages of schistosome to S83143 was similar to that of praziquantel.The acute LD50 of ig S83143 suspension was more than 10g/kg, while ED50 was 352?65 mg/kg. With im S85010 solution, the LD50 and ED50 were 176?14 and 66?10 mg/kg respectively. Therefore, the therapeutic index of S83143 was over 28, which was higher than 2.67 of S8S010.

OBSERVATION ON SUSCEPTIBILITY OF DIFFERENT GEOGRAPHIC SCHISTOSOMA JAPONICUM TO PRAZIQUANTEL IN MICE / 中国药理学通报

Mice, were each infected with 48-52 different geographic Schisto-soma japonicum cercariae of Zhejiang Hangzhou, Jiangsu Wuxi,Anhui Guchi,Jiangxi Nanchang,Hubei Hanyang , Hunan Yueyang & Yunnan Dali. 32-35 d after infection, the mice were treated orally with praziquantel at a single dose of 400 mg/kg. The worm reduction rates of each geographic S. japonicum were compared with that of Anhui Guchi schistosomes which was known to be more sensitive to praziquantel. The results showed that the worm reduction rate of Yunnan Dali schistosomes was 35.1%, which was much less than 75.4% of Anhui Guchi schistosomes. No apparent difference in susceptibility of other 5 geographic schistosomes to praziquantel was observed as comparing with Anhui Guchi schistosomes.When mice infected with Yunnan or Anhui schistosomes for 5 weeks were treated orally with praziquantel at a single dose of 300 mg/kg. the drug-induced hepatic shift rate of the worms and morphological changes of the worms were more or less similar in both geographic schistosomes within 28 d after medication. It was considered that less effect of praziquanfel on Yunnan Dali schistosomes may be ascribed to less susceptibility of the worms to the drug.