Protective effects of EDTA and EGTA against CCl<sub>4</sub>-induced acute hepatotoxicity in mice

Park, Seung-Guk; Cho, Yong-Do; Shin, Taekyun; Wie, Myung-Bok

Korean Journal of Veterinary Research 2007;47(3):265-271.

Protective effects of EDTA and EGTA against CCl₄-induced acute hepatotoxicity in mice

Seung-Guk Park¹, Yong-Do Cho¹, Taekyun Shin², Myung-Bok Wie¹

¹School of Veterinary Medicine, Kangwon National University (Institute of Veterinary Science)
²Department of Veterinary Medicine, Chueju National University

마우스에서 사염화탄소로 유발된 급성 간독성에 대한 EDTA 및 EGTA의 보호효과

박승국¹, 조용도¹, 신태균², 위명복¹

¹강원대학교 수의학부대학 (동물의학종합연구소)
²제주대학교 수의학과

Abstract

This study investigated the protective effects of ethylene glycol-bis(${eta}$-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA), an extracellular calcium chelator, and ethylenediaminetetraacetic acid (EDTA), which chelates calcium and most metal ions, against carbon tetrachloride ($CCl_4$)-induced acute hepatotoxicity in mice. Mice were treated with EGTA or EDTA at a dose of 20 (low) or 100 mg/kg (high) subcutaneously 1h before $CCl_4$ administration. The mice were fasted and sacrificed 18h after $CCl_4$ treatment. Blood samples were collected from the carotid artery by decapitation under light ether anesthesia. Serum alkaline phosphatase (ALP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), triglyceride (TG), and cholesterol levels were measured. Malondialdehyde (MDA) production was determined as an index of lipid peroxidation in the liver. The liver, kidneys, and spleen were weighed. We also evaluated the histopathological changes in the liver in each group. The relative weights of the liver were significantly higher in the $CCl_4$-treatment group than in the normal group, except in the high-EDTA treatment group. EGTA and EDTA treatment caused a significant decrease in serum ALP, ALT, and AST levels. Of all of the doses of EGTA and EDTA tested, the high-EDTA dose resulted in the most remarkable inhibitory action. The protective effect in the high-EDTA-treatment group was confirmed histopathologically. The low-EGTA-treatment group showed a significant decrease in serum TG and cholesterol levels. Liver MDA levels were significantly decreased in the EGTA (20 mg/kg) and EDTA (20, 100 mg/kg) groups. These results suggest that EDTA, which chelates both calcium and metal ions, confers better protection in $CCl_4$-induced acute liver damage than does EGTA, a calcium chelator.

Key Words: carbon tetrachloride, chelator, EDTA, EGTA, MDA