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Protective Effect of DWP-04 Against Hepatotoxicity Induced by D-galactosamine

흰쥐에서 DWP-04가 D-galactosamine에 의해 유도된 간독성의 보호효과

  • Published : 2005.06.01

Abstract

This study was conducted to investigate the biological activity and hepatoprotective effect of DWP-04 [DDB : selenium yeast: glutathione (31.1 : 6.8 : 62.1(w/w/w)] in D-galactosamine (GaIN) intoxicated rats. The DWP-04 (50, 100 or 200 mg/kg) or its vehicle was orally administered everyday before the start of GaIN injection (400 mg/kg, ip) for two weeks and animal decapitated for 24 hrs after GaIN­injected. The activities of serum enzymes, markers of liver function, were increased in the GaIN group compared to normal group and significantly lowered in the DWP-04 pretreated group than in the GaIN group. Hepatic lipid peroxide level and activities of phase 1 enzymes were significantly higher than those of GaIN group compared to normal group and lower in the DWP-04 pretreated group than in the GaIN group, and phase II enzyme activities in liver were lower in the GaIN group than in the normal group and were increased in the DWP-04 pretreated group than in the GaIN group. Total hepatic glutathione content and glutathione biosynthesis enzymes were lower in the GaIN group than in the normal group and were increased in the DWP-04 pretreated group than in the GaIN group. Therefore, the current results indicated that DWP-04 administration alleviated the GaIN-induced adverse effect through enhancing the antioxidant enzyme activities.

간기능 보호 작용이 있는 것으로 알려진 DDB, selenium과 glutathione의 혼합제제인 DWP-04의 간보호 작용을 검토할 목적으로 DWP-04를 실험동물에 경구로 투여하고서 D-galactosamine으로 간독성을 유발하여 혈액의 변동 및 간 조직에서의 활성산소 생성계 및 해독계의 활성에 미치는 영향을 관찰한 결과 GaIN의 단독투여는 대조군에 비하여 혈중 간 기능 지표효소 및 간 조직에서의 지질과산화의 함량이 현저히 증가하였으나, DWP-04의 전처리로 현저히 감소되었다. CaIN의 단독 투여로 활성산소의 생성계인 phase 1계의 효소가 현저히 증가하던 것이 DWP-04의 처리로 억제되었으며 해독계인 phase II계의 효소는 GaIN의 투여로 대조군에 비하여 억제되던 것이 DWP-04의 전처리로 정상군에는 미치지 않으나 유의성 있게 증가되었다. 간 조직중 glutathine의 함량은 CaIN의 투여로 현저히 억제되었으며 DWP-04의 투여로 증가하였는데 이러한 결과는 DWP-04의 투여로 glutathione peroxidase의 활성보다는 $\gamma-glutamylcysteine$ synthetase의 활성을 조절한 결과로 생각된다. 이상의 결과를 종합하여 볼 때 DWP-04의 투여는 활성산소의 생성 및 해독계를 조절하므로서 GaIN으로 인한 간손상을 보호하는 효과가 있는 것으로 사료된다.

Keywords

References

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