Pyrrolidine dithiocarbamate protects against thioacetamide-induced fulminant hepatic failure in rats.
OBJECTIVE
Reactive oxygen species and nuclear factor kappa B (NF-kappaB) activation have been implicated in the pathogenesis of cell injury in experimental models of liver damage. The aim of the present study was to examine whether pyrrolidine dithiocarbamate (PDTC), an anti oxidant and inhibitor of NF-kappaB activation, would prevent hepatic damage induced in a rat model of thioacetamide (TAA)-induced liver failure.


METHODS
Fulminant hepatic failure was induced in the control and treatment groups by two intraperitoneal injections of TAA (either 300 or 400 mg/kg) at 24-h intervals. In the treatment groups, rats were treated also with PDTC (60 mg/kg/24 h, i.p.), initiated 24 h prior to TAA.


RESULTS
Liver enzymes, blood ammonia, and hepatic levels of thiobarbituric acid reactive substances (P<0.001) and protein carbonyls (P<0.05) were significantly lower in rats treated with PDTC compared to TAA only. Liver histology and the survival rate in the PDTC-treated rats were also improved (P<0.01 compared to TAA only). NF-kappaB activation, 2 and 6 h after TAA administration, was inhibited by PDTC.


CONCLUSIONS
In a rat model of fulminant hepatic failure, the administration of PDTC attenuated liver damage and improved survival. This effect may be due to decreased oxidative stress and inhibition of NF-kappaB activation.
Bruck
Rafael
R
Department of Gastroenterology, E. Wolfson Medical Center, 58100, Holon, Israel. rbuck@wolfson.health.gov.il
Aeed
Hussein
H
Schey
Ron
R
Matas
Zipora
Z
Reifen
Ram
R
Zaiger
Gidi
G
Hochman
Ayala
A
Avni
Yona
Y
D000641:Ammonia / Q000097:blood; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000737:chemistry / Q000201:enzymology / Q000473:pathology; D017093:Liver Failure / Q000139:chemically induced / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D011506:Proteins / Q000032:analysis; D011759:Pyrrolidines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D015996:Survival Rate; D013853:Thioacetamide; D017392:Thiobarbituric Acid Reactive Substances / Q000032:analysis; D013859:Thiocarbamates / Q000494:pharmacology*; D000637:Transaminases / Q000097:blood
D000975:Antioxidants; D016328:NF-kappa B; D011506:Proteins; D011759:Pyrrolidines; D017382:Reactive Oxygen Species; D017392:Thiobarbituric Acid Reactive Substances; D013859:Thiocarbamates; D013853:Thioacetamide; C020972:pyrrolidine dithiocarbamic acid; D000641:Ammonia; D000637:Transaminases