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논문 기본 정보

자료유형
학술저널
저자정보
저널정보
한국실험동물학회 Laboratory Animal Research Laboratory Animal Research Vol.23 No.2
발행연도
2007.6
수록면
155 - 161 (7page)

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Aim of this study was to elucidate whether metabolic enzymes will cause a time-dependent liver injury and identify the relationship between hepatotoxicity and biochemical change in Sprague-Dawley (SD) rat treated with carbon tetrachloride (CCI₄), a well known hepatotoxicant. Acute hepatotoxicity was induced in male rats by a single oral administration of CCI₄ (1 ㎖/㎏), and then time coursed changes of biochemical markers were investigated through 72 hour (H). For determining the severity of hepatotoxicity, biochemical values such as serum alanine aminotransferase (ALT) and serum aspartate aminotransferase (AST) activities were analyzed, as well as liver morphology. In addition, cytochrome P450 (CYP) 2E1 and reduced glutathione (GSH) were measured to seek any relationships. The hepatic injuries induced by CCI₄ were pronounced up to 48H with the predominant sign of hepatocyte vacuolation including hepatocyte necrosis with inflammatory cell infiltration, which was recovered at 72H. These results were consistent with ALT, AST levels, which showed most severe elevation at 48H. In contrast to severe sign of hepatotoxicity at 48H in biochemical and histological observation, CYP2E1 protein expression was decreased to lowest level at 24H and showed a slight recovery at 48H, followed by a marked recovery at 72H. Assays for GSH had showed more variable changes of GSH with up-down-up pattern but the significant elevation was observed at 72H compared to untreated rats (P ＜ 0.05). This result showed that serum biochemical value was in a complete agreement with corresponding microscopic observations, and the expression of CYP2E1 protein levels had a large similarity with hepatic injury. Also, the results that CYP2E1 protein expression has a large similarity with hepatic injury provide a clear evidence that specific CYP enzyme activity measurement involved in the toxic activation of chemical, if it was performed at adequate time-point, will be a useful tool for toxico-dynamic assessment.
#Carbon tetrachloride(CCI₄) #acute hepatotoxicity #CYP2E1 #metabolism #reduced glutathione(GSH) #rats

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Material and Methods
Results
Discussion
References

참고문헌 (25)

참고문헌 신청
Abraham, P , 1999 , Oxidative damage to the lipids and proteins of the lungs, testis and kidney of rats during carbon tetrachloride intoxication 289 : 177 ~ 179 google schola Anzenbacher, P , 2001 , Cytochromes P450 and metabolism of xenobiotics 58 : 737 ~ 747 google schola Bertrand, M , 2000 , Rapid assessment of drug metabolism in the drug discovery process 11 : S61 ~ S72 google schola Constan, A.A , 1999 , Metabolism of chloroform by cytochrome P4502E1 is required for induction of toxicity in the liver, kidney, and nose of male mice 169 : 120 ~ 126 google schola Daniels, W.M , 1995 , Melatonin counteracts lipid peroxidation induced by carbon tetrachloride but does not restore glucose-6 phosphatase activity 19 : 1 ~ 6 google schola

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