Melatonin inhibits nuclear factor kappa B activation and oxidative stress and protects against thioacetamide induced liver damage in rats.
OBJECTIVE
Free radical-mediated oxidative stress has been implicated in the pathogenesis of acute liver injury. The aim of our study was to investigate whether melatonin, a potent free radical scavenger could prevent fulminant hepatic failure in rats.


METHODS
Liver damage was induced by two consecutive injections of thioacetamide (TAA, 300 mg/kg/i.p.) at 24 h intervals. Treatment with melatonin (3 mg/kg/daily, i.p) was initiated 24 h prior to TAA.


RESULTS
Twenty-four h after the second TAA injection, serum liver enzymes and blood ammonia were lower in rats treated with TAA+melatonin compared to TAA (P<0.001). Liver histology was significantly improved and the mortality in the melatonin-treated rats was decreased (P<0.001). The increased nuclear binding of nuclear factor kappa B in the livers of the TAA-treated rats, was inhibited by melatonin. The hepatic levels of thiobarbituric acid reactive substances, protein carbonyls and inducible nitric oxide synthase were lower in the TAA+melatonin-treated group (P<0.01), indicating decreased oxidative stress and inflammation.


CONCLUSIONS
In a rat model of TAA-induced fulminant hepatic failure, melatonin improves survival and reduces liver damage and oxidative stress. The results suggest a causative role of oxidative stress in TAA-induced hepatic damage and suggest that melatonin may be utilized to reduce liver injury associated with oxidative stress.
Bruck
Rafael
R
Department of Gastroenterology, The E. Wolfson Medical Center, Holon 58100, Israel. rbruck@wolfson.health.gov.il
Aeed
Hussein
H
Avni
Yona
Y
Shirin
Haim
H
Matas
Zipora
Z
Shahmurov
Mark
M
Avinoach
Ilana
I
Zozulya
Galina
G
Weizman
Nir
N
Hochman
Ayala
A
D000641:Ammonia / Q000097:blood; D000818:Animals; D056486:Chemical and Drug Induced Liver Injury; D016166:Free Radical Scavengers / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D008107:Liver Diseases / Q000378:metabolism / Q000517:prevention & control*; D008297:Male; D008550:Melatonin / Q000494:pharmacology*; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D015996:Survival Rate; D013853:Thioacetamide / Q000494:pharmacology; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
D016166:Free Radical Scavengers; D016328:NF-kappa B; D017392:Thiobarbituric Acid Reactive Substances; D013853:Thioacetamide; D000641:Ammonia; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D008550:Melatonin