Annals of Occupational and Environmental Medicine

The Korean Society of Occupational & Environmental Medicine (대한직업환경의학회)
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Acute Toxicity of Arsenic in Rats and Mice

랏트와 마우스에서 비소의 급성독성에 대한 연구

Choi, Byung-Sun;Kang, Dae-Woong;Lee, Jin-Young;Park, Eon-Sub;Hong, Yeon-Pyo;Yang, Ji-Sun;Lee, Hyo-Min;Park, Jung-Duck
최병선;강대웅;이진영;박언섭;홍연표;양지선;이효민;박정덕

  • Published : 20031200
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Abstract

Objectives: Arsenic (As) is ubiquitously distributed in the environment and is known as a human carcinogen. In this study, acute As toxicity at lethal dosage in rats and mice was evaluated, and As-induced hepatotoxicity was characterized. Methods: Male Sprague-Dawley rats, male ICR mice and trivalent inorganic As, sodium arsenite, were used in this experiment. $LD_{50}$ and $LD_{100}$ were calculated from 24-hour lethality after the single subcutaneous administration of As into rats and mice. Serum and liver were collected from the surviving animals. The activities of ALT, AST and $\gamma$-GT in serum were determined, and the concentrations of MDA, GSH and CYP450 in liver were analyzed. Results: The $LD_{50}$ and $LD_{100}$ of sodium arsenite were calculated as 12 mg/kg and 13 mg/kg for rats, and 16.5 mg/kg and 19 mg/kg for mice, respectively. Thus, the rat was more susceptible than the mouse to the acute lethal toxicity of As. The histopathological changes induced by As were similar between rats and mice. AST was increased in high-dose As-treated rats and mice, whereas ALT was increased in high-dose As-treated mice but not in rats. $\gamma$-GT was not significantly changed between the two animal groups. As increased lipid peroxidation, but decreased GSH and CYP450 in the liver of both rats and mice, in dose-dependent patterns. These results indicate that oxidative stress might be one of the mechanisms in As-induced hepatotoxicity. Conclusion: Rats were more susceptive than mice to acute As toxicity, and oxidative stress might play a part in liver injury induced by As.

목적: 비소(Arsenic)는 환경중에 널리 분포하는 금속물질로서 인간발암물질이다. 이번 연구에서는 2종의 실험동물을 대상으로 비소 투여량에 따른 치사율을 이용한 급성독성을 평가하였고, 간조직의 형태학적 소견과 혈청지표 및 간지표를 이용하여 간독성을 평가하였다. 방법: 실험동물은 male Sprague-Dawley 랏트와 male ICR 마우스를 사용하였고, 비소는 sodium arsenite 형태의 3가 무기비소를 이용하였다. 랏트와 마우스에 여러 단계별 용량의 비소를 1회 피하주사한 후 24시간에서의 치사율을 이용하여 $LD_{50}$과 $LD_{100}$을 산출하였다. 생존한 실험동물은 즉시 희생시켜 혈청과 간조직을 채취.분리하여 혈청에서는 ALT, AST 및 $\gamma$-GT 활성도를 측정하였고, 간조직에서는 지질과산화반응, GSH 및 CYP450 농도를 분석하였다. 결과: 랏트에 대한 3가 무기비소의 $LD_{50}$과 $LD_{100}$은 12 mg/kg와 13 mg/kg 이었고, 마우스에서는 $LD_{50}$ 16.5 mg/kg, $LD_{100}$ 19 mg/kg 로서 랏트가 마우스에 비해 비소의 급성독성에 민감하였다. 비소에 의한 간조직의 형태학적 이상소견은 랏트와 마우스에서 비슷한 양상으로 관찰되었으나, 랏트가 마우스보다 민감한 것으로 나타났다. 혈청 AST 활성도는 비소 고농도군에서는 대조군에 비해 증가되었으나, ALT는 마우스의 고농도군에서만 증가되었고 $\gamma$-GT는 뚜렷한 변화가 관찰되지 않았다. 랏트와 마우스 모두에서 비소 투여량이 증가함에 따라 간조직에서 지질과산화반응이 증가되었고, GSH와 CYP450 농도는 감소되었다. 이러한 결과는 비소에 의한 산소 산화성 손상이 간독성의 한 기전으로 작용함을 시사한다. 결론: 비소의 급성독성은 랏트가 마우스에 비해 민감하였고, 비소에 의한 간독성 기전의 하나로서 산소 산화성 손상이 관여하는 것으로 사료된다.

Keywords

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