Effects of Vitamin E on the Metallothionein Synthesis in Streptozotocin-induced Diabetic Rats

Streptozotocin유발 당뇨쥐에 있어서 Metallothionein 합성에 미치는 비타민 E의 영향

  • 이순재 (대구효성카톨릭대학교 식품영양학과) ;
  • 최원경 (대구효성카톨릭대학교 식품영양학과)
  • Published : 1995.04.01

Abstract

The purpose of this study was to investigate the effect of vitamin E on the synthesis of the metallothionein in the liver of streptozotocin (STZ)-induced diabetic rats. Sprague-Dawley male rats($220{\pm}10mg$) were randomly assigned to one control and three STZ-diabetic groups. Diabetic groups were classified to STZ-0E(vitamine E free diet), STZ-40E(40mg vitamin E/kg of diet) and STZ-400E(400mg vitamin E/kg of diet) according to the level of vitamin E supplementation. Blood glucose levels of STZ-diabetic rats were three times higher than that of control. The contents of vitamin E in liver were lower signifciantly STZ-0E, STZ-40E groups by 50%, 36% compared with that of control. Lipid peroxide values(LPO) in liver were higher 5.6 and 2.5 times in STZ-0E and STZ-40E groups than that of control. Plasma cortisol levels were higher STZ-0E and STZ-40E groups compared with those of control, but cortisol levels were lower significantly in STZ-400E group compared with those of the STZ-0E and the STZ-40E groups. The plasma insulin levels were lower in all three STZ-diabetic group compared with that of control, but were not affected by the level of dietary vitamin E. The metallothionein (MT) contents in liver, kidney and small intestine were five times higher in STZ-0E, STZ-40E and STZ-400E compared with that of control, but STZ-400E group was lower in the MT contents in tissues compared with that of STZ-40E group. Zn-MT peak in STZ-diabetic rats liver increased than that of control by Sephadex G-75, and Zn-MT peak divided into MTI and MTII peaks by DEAE Sephadex A-25 column chromatography. The present results indicate that STZ-induced diabetic rats are more sensitive to oxidative stress, leading to the acceleration of lipid peroxidation process, which can be more promoted low level of dietary vitamin E. And the result may that increase synthesis of MT induced in the liver of diabetic rats increased so it can be sure that the diabetes is one of the MT induce factor by free radical generation. And high vitamin E supplementation reduced total MT contents of liver, kidney and small intestine and the peak of purified Zn-MT. Through the results of these experiments, we can conclude that MT might be the free radical scavenger.

식이내 비타민 E 함량을 0mg vit. E/kg diet(STZ-OE군), 40mg vit. E/kg diet(STZ-40E군) 그리고 40mg vit. E/kg diet(STZ-400E군)로 달리하여 4주간 사육한 후 streptozotocin으로 당뇨병을 유발한 후 4일째에 희생시켜, 당뇨병 쥐에 있어서 MT합성에 미치는 비타민 E의 영향을 관찰한 결과는 다음과 같다. 체중증가는 STZ을 투여하기 전까지는 대조군에 비해 STZ-0E군만 낮았으나 STZ투여한 후에는 STZ투여군들 모두가 현저하게 감소하였다. 실험군간을 비교해 보면 STZ-400E군이 STZ-0E, STZ-40E군에 비해 STZ을 투여한 후 감소율이 낮았다. 혈당량은 당뇨군들이 대조군에 비해 약 3배 정도 높았으나, 당뇨군들 중에서 비타민 E의 영향은 없었다. 간조직 중의 비타민 E 함량은 STZ-0E 및 STZ-40E군에서는 대조군 보다 각각 50, 36%씩 크게 감소되었으나 STZ-400E군은 차이가 없었다. Glutathione(GSH) 함량은 비타민 E의 다량 첨가군(STZ-400E)에서 GSH 함량과 GSH/GSSG비가 증가되었다. 간조직 중의 지질과산화가는 STZ-0E군과 STZ-40E군이 대조군 보다 5.6, 2.5배씩 높았으나 STZ-400E군은 유의적인 차이가 없었다. Piasma insulin level은 대조군에 비해 당뇨유발군 모두가 현저하게 감소하였고, 비타민 E의 효과는 관찰되지 않았다. Piasma cortisol level은 대조군에 비해 STZ-0E, STZ-40E군이 증가하였으나 STZ-400E군은 이들 두군에 비해 유의적으로 감소하여 대조군 수준이었다. 간장, 신장, 소장조직의 MT 함량은 대조군에 비해 당뇨유발군이 각각 5.3, 2.8, 16배 정도 현저히 증가되었는데 STZ-400E군은 STZ-0E, STZ-40E 이들 두군에 비해 현저하게 감소되었다. Sephadex G-75를 사용하여 간조직 중의 Zn-MT를 분리한 결과 당뇨 유발군에서 대조군 보다 Zn-MT peak가 증가되었으나 Cu-MT는 변화가 없었다. Zn-MT는 DEAE A-25를 사용하여 MTI, MTII peak를 확인할 수 있었다. 이상의 결과에서 STZ유발 당뇨쥐는 산화적 stress에 더욱 감수성이 높으므로 지질과 산화 반응이 정상군에 비해 촉진되었으며, 식이 중 공급되는 비타민 E 함량이 부족시는 더욱 가속화되었다. 더불어 간조직 중의 MT합성도 같은 양상으로 증가되어 당뇨병이 free radical 생성으로 인해 MT를 유도하는 하나의 새로운 인자인 것으로 확인하였다. 그러나 식이 중 비타민 E의 다량 급여시는 생체내 항산화계 효소들이 정상군에 가깝게 활성화되고, 생리적 항산화물질이 증가되었다. 따라서 식이비타민 E가 당뇨병으로 인한 지질과산화에 대한 항산화적 방어기구를 강화시키므로써 조직의 과산화적 손상을 환화시키는데 크게 기여함을 알 수 있었다. 또한 비타민 E 다량 투여로 간조직과 신장, 소장조직내의 total MT 함량이 감소되고 분리정제한 Zn-MT의 peak가 감소하는 것으로 보아 MT가 free radical scavenger로서 작용한 것이라고 생각된다.

Keywords

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