Gliotoxin ameliorates development of fibrosis and cirrhosis in a thioacetamide rat model.
Activation of hepatic stellate cells causes most of the pathological changes in cirrhosis. The fungal metabolite gliotoxin was shown to induce apoptosis of hepatic stellate cells in vitro. We examined whether gliotoxin may prevent or reverse liver fibrosis in a rat model of thioacetamide-induced cirrhosis, and whether gliotoxin administration in vivo causes apoptosis of activated stellate cells. Gliotoxin treatment resulted in a significant decrease in liver fibrosis in rats, but did not improve liver functions. We observed a significant reduction in the numbers of activated hepatic stellate cells in the gliotoxin-treated rats. Gliotoxin administration also resulted in parenchymal apoptosis of hepatocytes and hepatic stellate cells. In conclusion, gliotoxin reduces hepatic fibrosis, an effect accompanied by reduction of the numbers of activated hepatic stellate cells in the liver.
Dekel
Roy
R
Internal Medicine H, Tel Aviv Sourasky Medical Center, Weizmann 6, Tel Aviv, Israel 64239.
Zvibel
Isabel
I
Brill
Shlomo
S
Brazovsky
Eli
E
Halpern
Zamir
Z
Oren
Ran
R
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002452:Cell Count; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005912:Gliotoxin / Q000494:pharmacology*; D022781:Hepatocytes / Q000187:drug effects / Q000473:pathology; D020287:In Situ Nick-End Labeling; D008106:Liver Cirrhosis, Experimental / Q000139:chemically induced / Q000473:pathology*; D051381:Rats; D011916:Rats, Inbred F344; D013853:Thioacetamide
D013853:Thioacetamide; D005912:Gliotoxin