Rosiglitazone prevents murine hepatic fibrosis induced by Schistosoma japonicum.
OBJECTIVE
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.


CONCLUSIONS
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.
Chen
Hui
H
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
He
Yong-Wen
YW
Liu
Wen-Qi
WQ
Zhang
Jing-Hui
JH
D000199:Actins / Q000378:metabolism; D000818:Animals; D000871:Anthelmintics / Q000494:pharmacology; D024042:Collagen Type I / Q000378:metabolism; D024061:Collagen Type III / Q000378:metabolism; D004195:Disease Models, Animal; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D015850:Interleukin-6 / Q000097:blood; D008099:Liver / Q000469:parasitology / Q000473:pathology; D008103:Liver Cirrhosis / Q000469:parasitology* / Q000473:pathology / Q000517:prevention & control*; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism; D011223:Praziquantel / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D000077154:Rosiglitazone; D012549:Schistosoma japonicum; D012554:Schistosomiasis japonica / Q000150:complications* / Q000188:drug therapy; D045162:Thiazolidinediones / Q000494:pharmacology*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D000199:Actins; D000871:Anthelmintics; D024042:Collagen Type I; D024061:Collagen Type III; D007004:Hypoglycemic Agents; D015850:Interleukin-6; D016328:NF-kappa B; D047495:PPAR gamma; D012333:RNA, Messenger; D045162:Thiazolidinediones; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha; D000077154:Rosiglitazone; D011223:Praziquantel