Curcumin ameliorates acute thioacetamide-induced hepatotoxicity.
OBJECTIVE
Increased production of reactive oxygen species and nitric oxide and activation of nuclear factor kappa B are implicated in the pathogenesis of various liver diseases, including fulminant hepatic failure. Curcumin is a naturally occurring anti-oxidant that reduces oxidative stress and inhibits nuclear factor kappa B and nitric oxide formation. The aim of the present study is to assess curcumin's therapeutic potential in acute thioacetamide hepatotoxicity, a rat model of fulminant hepatic failure.


METHODS
Fulminant hepatic failure was induced by two intraperitoneal (i.p.) injections of 300 mg/kg thioacetamide (TAA) at 24-h intervals. The experimental groups received a low-dose (200 mg/kg per day, i.p.) or a high-dose (400 mg/kg per day) of curcumin, initiated 48 h prior to the first TAA injection. A fourth group was administered neither TAA nor curcumin and served as a control.


RESULTS
The survival rate was higher in both curcumin-treated groups compared to the TAA only treated group. Biochemical parameters of liver injury, blood ammonia and hepatic necroinflammation were lower in the low-dose curcumin group compared to TAA controls, and were further reduced in the high-dose group (P < 0.05 and P < 0.01, respectively). Curcumin treatment also reduced the TAA-induced elevated hepatic levels of thiobarbituric acid-reactive substances (TBARS), and inhibited the nuclear binding of nuclear factor kappa B (NFkappaB) and inducible nitric oxide (iNOS) protein expression.


CONCLUSIONS
Curcumin improved survival and minimized oxidative stress, hepatocellular injury and hepatic necroinflammation, NFkappaB binding and iNOS expression in a rat model of FHF. These findings support the role of ROS, NFkappaB and iNOS in mediating liver insult due to TAA, and that of curcumin as a hepato-protectant.
Shapiro
Haim
H
The Unit of Clinical Hypnosis, The E. Wolfson Medical Center, Holon and Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
Ashkenazi
Michal
M
Weizman
Nir
N
Shahmurov
Mark
M
Aeed
Hussein
H
Bruck
Rafael
R
D000818:Animals; D003474:Curcumin / Q000008:administration & dosage / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D017114:Liver Failure, Acute / Q000139:chemically induced / Q000188:drug therapy* / Q000201:enzymology; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D013853:Thioacetamide / Q000633:toxicity; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D016896:Treatment Outcome
D004791:Enzyme Inhibitors; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D017392:Thiobarbituric Acid Reactive Substances; D013853:Thioacetamide; D052247:Nitric Oxide Synthase Type II; D003474:Curcumin