JPP 2006, 58: 143–152 © 2006 The Authors Received August 9, 2005 Accepted September 28, 2005 DOI 10.1211/jpp.58.1.0018 ISSN 0022-3573 143 Protective effect of glycoprotein isolated from Ulmus davidiana Nakai on carbon tetrachloride-induced mouse liver injury Sei-Jung Lee, Phil-Sun Oh, Jeong-Hyeon Ko, Kwang Lim and Kye-Taek Lim Abstract This study was carried out to evaluate the hepatoprotective activity of glycoprotein isolated from the stems of Ulmus davidiana Nakai (UDN), which has been used as an anti-inflammatory agent in folk medicine. We evaluated lipid peroxidation in glucose/glucose oxidase (G/GO)-induced BNL CL.2 cells and measured thiobarbituric acid reactive substances (TBARS), lactate dehydrogenase (LDH), nitric oxide (NO), antioxidant enzyme (superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx)), activity of cytotoxic-related signals (hepatic cytochrome c, nuclear factor-kappa B (NF-B) and activator protein-1 (AP-1)) and levels of plasma lipids (triglyceride (TG) and total choles- terol (TC)) in carbon tetrachloride (CCl 4, 1.0 mL kg -1 )-induced A/J mouse. The results in G/GO- induced BNL CL.2 cells showed that UDN glycoprotein had a dose-dependent inhibitory effect on lipid peroxidation. The results in carbon tetrachloride (CCl 4, 1.0 mL kg -1 )-induced A/J mouse indi- cated that treatment with UDN glycoprotein (40 mg kg -1 ) lowered LDH activity and TBARS forma- tion, and increased NO production and antioxidant enzymes activity, compared with control. Also, our finding from CCl 4 -treated mice after pretreatment with UDN glycoprotein demonstrated that the activity of cytotoxic-related signals decreased but the levels of plasma lipids increased, com- pared with CCl 4 treatment alone. Here, we speculate that UDN glycoprotein has a protective charac- ter to CCl 4 -induced mouse liver injury. Reactive oxygen species (ROS) cause extensive damage to DNA, proteins and lipids and have been implicated in the initiation of various liver pathological processes, such as fibro- genesis, cirrhosis and steatosis (Cesaratto et al 2004). The main sources of ROS generation in the liver are represented by mitochondria and cytochrome P450 system in hepatocytes, Kupffer cells and neutrophils. Although ROS production cannot be avoided in the meta- bolic pathway, there is an antioxidant defence system for detoxifying oxygen radicals. This antioxidant defence system, consisting of enzymatic (superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx)) and non-enzymatic (ascorbic acid, glutathione and -tocopherol) compounds, can maintain the balance between ROS generation and pro- tection from damage by ROS (Jaeschke et al 2002; Cesaratto et al 2004). Carbon tetrachloride (CCl 4 ) is widely used as a hepatotoxic compound for screening the anti-hepatotoxic/hepatoprotective activity of drugs in experimental model systems, because CCl 4 -induced hepatotoxicity is regarded as an analogue of liver injury caused by a variety of hepatotoxins in man. It has been generally reported and accepted that CCl 4 -induced hepa- totoxicity results from its hepatotoxic metabolites and trichloromethyl free radical (•CCl 3 ) (Recknagel & Glende 1973). This free radical can react with sulfhydryl groups, such as glu- tathione (GSH) and thiol-groups in the protein side chain. Also it covalently binds with cell proteins, and then initiates the lipid peroxidation process in the cellular membrane, which eventually leads to various liver pathological processes (Connor et al 1990; Williams & Burk 1990). Therefore, one of the therapeutic strategies against liver injury and disease is to find antioxidant compounds that are able to block liver injury through scavenging of trichlo- romethyl free radical generated by CCl 4 . CCl 4 is one of the well-known promoters of nuclear factor-kappa B (NF-B) and activator protein-1 (AP-1) in the apoptotic response of hepatocytes, inflammatory response of Kupffer Introduction Molecular Biochemistry Laboratory, Institute of Biotechnology, Chonnam National University, Kwangju, 300 Yongbong-Dong, 500-757, South Korea. Sei-Jung Lee, Phil-Sun Oh, Jeong-Hyeon Ko, Kye-Taek Lim Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, British Columbia, Canada V6T 1Z3 Kwang Lim Correspondence: K. T. Lim, Molecular Biochemistry Laboratory, Institute of Biotechnology, Chonnam National University, Kwangju, 300 Yongbong-Dong, 500-757, South Korea. E-mail: ktlim@chonnam.ac.kr; kyetaeklim@hotmail.com