HEPATOPROTECTIVE EFFECT OF GAMAVUTON-0 AGAINST D˗GALACTOSAMINE/LIPOPOLYSACCHARIDE-INDUCED FULMINANT HEPATIC FAILURE
The objective of this study is to determine the hepatoprotective effect of GVT-0 (one of curcumin analogues) against liver damage in rat-induced D-galactosamine (D-GalN)/lipopolysaccharide (LPS) as a model of fulminant hepatitis. In the study D˗GalN/LPS elevated serum GPT activity that indicate a particular occurrence of liver damage due to depletion of UTP and UDP-glucuronic acid. Administration of GVT-0 (10 mg/kg) showed decreased enzyme activity of SGPT/SGOT but had no effect on serum ALP and total bilirubin levels, whereas at doses of 20 and 40 mg/kg, the protective effect of GVT-0 was decrease. The glutathione content in the D-GalN/LPS (0.76 ± 0.07) mol/g liver content was found lower than controls (0.90 ± 0.03) mol/g liver. Administration of GVT-0 dose of 10, 20 and 40 mg/kg restored glutathione content returned to normal levels. The results showed that treatment of GVT-0 showed no effect on TBARS and catalase activity. Treatment of D-GalN/LPS, indicating the trend of increased TNF-α, although statistically not significant, while the administration of GVT-0 showed a tendency to decrease the concentration of TNF-α. All findings of the results indicated that the GVT-0 mainly lower dose (10 mg/kg) showed hepatoprotective action in rat model of fulminant hepatitis induced by D-GalN/LPS. The results indicated that the mechanism of hepatoprotective effect of GVT-0 is not via antioxidant properties of GVT-0. However, further studies are necessary to explain the molecular mechanism of hepatoprotective effect of GVT-0.
Key words: Gamavuton-0, hepatoprotective, fulminan hepatitis, D˗galactosamine/LPS
Aebi H., 1974, Catalase. In: Bergmeyer HV, editor. Methods in Enzymatic Analysis. Vol 2, New York: Acad. Press, p.674–684.
Chosay JG, Essani NA, Dunn CJ, and Jaeschke H., 1997, Neutrophil margination and extravasation in sinusoids and venules of liver during endotoxin-induced injury. Am J Physiol272: G1195–G1200.
Decker K., 1990, Biologically active products of stimulated liver macrophages (Kupffer cells). Eur J Biochem192:245–261.
Decker K, and Keppler D., 1974, Galactosamine hepatitis. Key role of the nucleotide deficiency period in the pathogenesis of cell injury and cell death. Rev Physiol Biochem Pharmacol 71:77–106.
Deshpande UR, Gadre SG, Raste AS, Pillai D, Bhide SV, and Samuel AM., 1998, Protective effect of turmeric (Curcuma longa L.) extract on carbon tetrachlorideinduced liver damage in rats. Indian J Exp Biol36:573577.
Donatus IA, Sardjoko, and Vermeulen NP., 1990, Cytotoxic and cytoprotective activities of curcumin. Effects on paracetamol-induced cytotoxicity, lipid peroxidation and glutathione depletion in rat hepatocytes. Biochem Pharmacol 39:18691875.
Ellman GL. 1959, Tissue sulphydryl groups. Arch Biochem Biophys 82:70 77.
Galanos C, Freudenberg MA, and Reutter W., 1979, Galactosamine-induced sensitization to the lethal effects of endotoxin. Proc Natl Acad Sci USA76:5939-5943.
Gregus Z, Madhu C, Goon D, and Klaassen CD., 1988, Effect of galactosamineinduced hepatic UDP-glucuronic acid depletion on acetaminophen elimination in rats. Dispositional differences between hepatically and extrahepatically formed glucuronides of acetaminophen and other chemicals. Drug Metab Dispos 16:527–533.
Jollow DJ., 1980, Glutathione thresholds in reactive metabolite toxicity, Arch Toxicol Suppl, 122:507-508.
Jonker AM, Dijkhuis FW, Kroese FG, Hardonk MJ, and Grond J., 1990, Immunopathology of acute galactosamine hepatitis in rats. Hepatology 11:622–627.
Kasravi FB, Wang L, Wang X, Molin G, Bengmark S, and Jeppsson B., 1996, Bacterial translocation in acute liver injury induced by D-galactosamine. Hepatology 23:97–103.
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