Hui Chen1, Yong-Wen He, Wen-Qi Liu, Jing-Hui Zhang. 1. Department of Infectious Disease, Union Hospital, Tongji Medical college, Huazhong University of Science and Technology, 1277# Jiefang Road, Wuhan 430022, Hubei Province, China. chenhui0515@yahoo.com.cn
Abstract
AIM: To evaluate the effect of rosiglitazone in a murine model of liver fibrosis induced by Schistosoma japonicum infection. METHODS: A total of 50 mice were randomly and averagely divided into groups A, B, C, D and E. The mice in group A served as normal controls, while those in the other four groups were infected with Schistosoma japonicum to induce the model of liver fibrosis. Besides, the mice in groups C, D and E were treated with praziquantel, rosiglitazone and praziquantel plus rosiglitazone, respectively. NF-kappaB binding activity and expression of PPAR gamma-mRNA were determined by Western blot assay and real-time quantitative PCR. Radioimmunonassay technique was used to detect the serum content changes of TNF-alpha and IL-6. Histological specimens were stained with HE. Expression of TGF-beta1, a-smooth muscle actin and type I and type III collagen was detected by immunohistochemistry and multimedia color pathographic analysis system. RESULTS: Inflammation and fibrosis in the rosiglitazone plus praziquantel treatment group (group E) were lightest among the mice infected with Schistosoma (P < 0.05). To further explore the mechanism of rosiglitazone action, we found that rosiglitazone can significantly increase the expression of PPAR gamma [E: -18.212 +/- (-3.909) vs B: -27.315 +/- (-6.348) and C: -25.647 +/- (-5.694), P < 0.05], reduce the NF-kappaB binding activity (E: 88.89 +/- 19.34 vs B: 141.11 +/- 15.37, C: 112.89 +/- 20.17 and D: 108.89 +/- 20.47, P < 0.05), and lower the serum level of TNF-alpha (E: 1.613 +/- 0.420 ng/mL vs B: 2.892 +/- 0.587 ng/mL, C: 2.346 +/- 0.371 ng/mL and D: 2.160 +/- 0.395 ng/mL, P < 0.05) and IL-6 (E: 0.106 +/- 0.021 ng/mL vs B: 0.140 +/- 0.031 ng/mL and C: 0.137 +/- 0.027 ng/mL, P < 0.05) in mice with liver fibrosis. Rosiglitazone can also substantially reduce the hepatic expression of TGF-beta1, alpha-SMA type I and type III collagen in mice with liver fibrosis. CONCLUSION: The activation of PPAR gamma by its ligand can retard liver fibrosis and suggest the use of rosiglitazone for the treatment of liver fibrosis due to Schistosoma japonicum infection.
AIM: To evaluate the effect of rosiglitazone in a murine model of liver fibrosis induced by Schistosoma japonicum infection. METHODS: A total of 50 mice were randomly and averagely divided into groups A, B, C, D and E. The mice in group A served as normal controls, while those in the other four groups were infected with Schistosoma japonicum to induce the model of liver fibrosis. Besides, the mice in groups C, D and E were treated with praziquantel, rosiglitazone and praziquantel plus rosiglitazone, respectively. NF-kappaB binding activity and expression of PPAR gamma-mRNA were determined by Western blot assay and real-time quantitative PCR. Radioimmunonassay technique was used to detect the serum content changes of TNF-alpha and IL-6. Histological specimens were stained with HE. Expression of TGF-beta1, a-smooth muscle actin and type I and type III collagen was detected by immunohistochemistry and multimedia color pathographic analysis system. RESULTS: Inflammation and fibrosis in the rosiglitazone plus praziquantel treatment group (group E) were lightest among the mice infected with Schistosoma (P < 0.05). To further explore the mechanism of rosiglitazone action, we found that rosiglitazone can significantly increase the expression of PPAR gamma [E: -18.212 +/- (-3.909) vs B: -27.315 +/- (-6.348) and C: -25.647 +/- (-5.694), P < 0.05], reduce the NF-kappaB binding activity (E: 88.89 +/- 19.34 vs B: 141.11 +/- 15.37, C: 112.89 +/- 20.17 and D: 108.89 +/- 20.47, P < 0.05), and lower the serum level of TNF-alpha (E: 1.613 +/- 0.420 ng/mL vs B: 2.892 +/- 0.587 ng/mL, C: 2.346 +/- 0.371 ng/mL and D: 2.160 +/- 0.395 ng/mL, P < 0.05) and IL-6 (E: 0.106 +/- 0.021 ng/mL vs B: 0.140 +/- 0.031 ng/mL and C: 0.137 +/- 0.027 ng/mL, P < 0.05) in mice with liver fibrosis. Rosiglitazone can also substantially reduce the hepatic expression of TGF-beta1, alpha-SMA type I and type III collagen in mice with liver fibrosis. CONCLUSION: The activation of PPAR gamma by its ligand can retard liver fibrosis and suggest the use of rosiglitazone for the treatment of liver fibrosis due to Schistosoma japonicum infection.
Authors: Patricia C Cogswell; David F Kashatus; Jayne A Keifer; Denis C Guttridge; Julie Y Reuther; Cindy Bristow; Sophie Roy; Donald W Nicholson; Albert S Baldwin Journal: J Biol Chem Date: 2002-11-13 Impact factor: 5.157
Authors: P P Simeonova; R M Gallucci; T Hulderman; R Wilson; C Kommineni; M Rao; M I Luster Journal: Toxicol Appl Pharmacol Date: 2001-12-01 Impact factor: 4.219