HEPATOPROTECTIVE EFFECT OF GAMAVUTON-0 AGAINST D˗GALACTOSAMINE/LIPOPOLYSACCHARIDE-INDUCED FULMINANT HEPATIC FAILURE

Arief Nurrochmad, Ika Puspita Sari, Retno Murwanti, Sardjiman ., Triana Candraningrum, Dyah Afritasari, Devina Martina, Iren Wati Siahaan

Abstract


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

 


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References


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 Biol36:573577.

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 39:18691875.

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.




DOI: http://dx.doi.org/10.14499/indonesianjpharm23iss1pp18-26

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