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פותח על ידי קלירמאש פתרונות בע"מ -
A protective effect of pyrrolidine dithiocarbamate in a rat model of liver cirrhosis
Year:
2004
Source of publication :
Liver International
Authors :
גנין, אולגה
;
.
פינס, מרק
;
.
Volume :
24
Co-Authors:
Bruck, R., Department of Gastroenterology, The E. Wolfson Medical Center, Holon 58100, Israel, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel
Schey, R., Department of Gastroenterology, The E. Wolfson Medical Center, Holon 58100, Israel, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel
Aeed, H., Department of Gastroenterology, The E. Wolfson Medical Center, Holon 58100, Israel, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel
Hochman, A., Department of Biochemistry, Faculty of Life Sciences, Tel-Aviv University, Tel-Aviv, Israel
Genina, O., Institute of Animal Science, Agriculture Research Organization, The Volcani Center, Bet Dagan, Israel
Pines, M., Institute of Animal Science, Agriculture Research Organization, The Volcani Center, Bet Dagan, Israel
Facilitators :
From page:
169
To page:
176
(
Total pages:
8
)
Abstract:
Background and Aims: Nuclear factor kappa B (NF-κB) activation, proinflammatory cytokines, and reactive oxygen species have been implicated as mediators of liver injury and fibrogenesis. We have shown recently that pyrrolidine dithiocarbamate (PDTC), an antioxidant and inhibitor of NF-κB activation, was protective in a rat model of acute liver failure. The aim of the present study was to examine the efficacy of PDTC in a chronic rat model of thioacetamide (TAA)-induced hepatic fibrosis. Methods: Liver cirrhosis was induced by intraperitoneal injections of TAA (200mg/kg) twice weekly for 12 weeks. Two groups of rats also received PDTC (either 20 or 60 mg/kg, i.p. for 12 weeks). Results: TAA administration induced liver cirrhosis, which was inhibited by PDTC in a dose-dependent manner. The histopathologic score of fibrosis, the spleen weight, and hepatic hydroxyproline were significantly lower in the rats treated with TAA+PDTC compared with TAA only (P<0.001). The hepatic levels of thiobarbituric acid reactive substances and protein carbonyls after 12 weeks of treatment were also lower in the rats treated with TAA+PDTC (P = 0.02 and 0.01, respectively), indicating reduced oxidative stress. Immunohistochemical studies and in situ hybridization demonstrated inhibition of stellate cell (α smooth muscle actin positive) activation, tissue inhibitor of metalloproteinase-2, and collagen α1(I) gene expression in the livers of the PDTC-treated rats. As determined by Northern blot analysis, PDTC had no inhibitory effect on collagen α1(I) gene expression in the rat hepatic stellate cells-T6 cells in vitro. Conclusions: PDTC inhibits the development of liver cirrhosis in TAA-treated rats. The mechanism of action is associated with decreased oxidative stress and hepatic necroinflammation. © Blackwell Munksgaard 2004.
Note:
Related Files :
animal experiment
Animals
antioxidants
Cell Line, Transformed
gene expression
hydroxyproline
Injections, Intraperitoneal
Male
עוד תגיות
תוכן קשור
More details
DOI :
Article number:
Affiliations:
Database:
סקופוס
Publication Type:
מאמר
;
.
Language:
אנגלית
Editors' remarks:
ID:
24721
Last updated date:
02/03/2022 17:27
Creation date:
17/04/2018 00:09
Scientific Publication
A protective effect of pyrrolidine dithiocarbamate in a rat model of liver cirrhosis
24
Bruck, R., Department of Gastroenterology, The E. Wolfson Medical Center, Holon 58100, Israel, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel
Schey, R., Department of Gastroenterology, The E. Wolfson Medical Center, Holon 58100, Israel, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel
Aeed, H., Department of Gastroenterology, The E. Wolfson Medical Center, Holon 58100, Israel, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel
Hochman, A., Department of Biochemistry, Faculty of Life Sciences, Tel-Aviv University, Tel-Aviv, Israel
Genina, O., Institute of Animal Science, Agriculture Research Organization, The Volcani Center, Bet Dagan, Israel
Pines, M., Institute of Animal Science, Agriculture Research Organization, The Volcani Center, Bet Dagan, Israel
A protective effect of pyrrolidine dithiocarbamate in a rat model of liver cirrhosis
Background and Aims: Nuclear factor kappa B (NF-κB) activation, proinflammatory cytokines, and reactive oxygen species have been implicated as mediators of liver injury and fibrogenesis. We have shown recently that pyrrolidine dithiocarbamate (PDTC), an antioxidant and inhibitor of NF-κB activation, was protective in a rat model of acute liver failure. The aim of the present study was to examine the efficacy of PDTC in a chronic rat model of thioacetamide (TAA)-induced hepatic fibrosis. Methods: Liver cirrhosis was induced by intraperitoneal injections of TAA (200mg/kg) twice weekly for 12 weeks. Two groups of rats also received PDTC (either 20 or 60 mg/kg, i.p. for 12 weeks). Results: TAA administration induced liver cirrhosis, which was inhibited by PDTC in a dose-dependent manner. The histopathologic score of fibrosis, the spleen weight, and hepatic hydroxyproline were significantly lower in the rats treated with TAA+PDTC compared with TAA only (P<0.001). The hepatic levels of thiobarbituric acid reactive substances and protein carbonyls after 12 weeks of treatment were also lower in the rats treated with TAA+PDTC (P = 0.02 and 0.01, respectively), indicating reduced oxidative stress. Immunohistochemical studies and in situ hybridization demonstrated inhibition of stellate cell (α smooth muscle actin positive) activation, tissue inhibitor of metalloproteinase-2, and collagen α1(I) gene expression in the livers of the PDTC-treated rats. As determined by Northern blot analysis, PDTC had no inhibitory effect on collagen α1(I) gene expression in the rat hepatic stellate cells-T6 cells in vitro. Conclusions: PDTC inhibits the development of liver cirrhosis in TAA-treated rats. The mechanism of action is associated with decreased oxidative stress and hepatic necroinflammation. © Blackwell Munksgaard 2004.
Scientific Publication
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