TY - JOUR
T1 - Melatonin inhibits nuclear factor kappa B activation and oxidative stress and protects against thioacetamide induced liver damage in rats
AU - Bruck, Rafael
AU - Aeed, Hussein
AU - Avni, Yona
AU - Shirin, Haim
AU - Matas, Zipora
AU - Shahmurov, Mark
AU - Avinoach, Ilana
AU - Zozulya, Galina
AU - Weizman, Nir
AU - Hochman, Ayala
PY - 2004/1
Y1 - 2004/1
N2 - Background/Aims: 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 κB 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.
AB - Background/Aims: 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 κB 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.
KW - Fulminant hepatitis
KW - Melatonin
KW - Oxidative stress
KW - Thioacetamide
UR - http://www.scopus.com/inward/record.url?scp=0346059342&partnerID=8YFLogxK
U2 - 10.1016/S0168-8278(03)00504-X
DO - 10.1016/S0168-8278(03)00504-X
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AN - SCOPUS:0346059342
SN - 0168-8278
VL - 40
SP - 86
EP - 93
JO - Journal of Hepatology
JF - Journal of Hepatology
IS - 1
ER -