title: Preventive effects of ZPDC glycoprotein (24 kDa) on hepatotoxicity induced by mercury chloride in vitro and in vivo.
abstract: Mercury is a potent environmental contaminant that exerts toxic effect on various vital organs in the human body. Recently, we isolated glycoprotein from Zanthoxylum piperitum DC (ZPDC), which has antioxidant and anticancer effects. In the present study, we determined the preventive effects of ZPDC glycoprotein on hepatic damage induced by mercury chloride (HgCl2 ). We evaluated the activities of lactate dehydrogenase (LDH), alanine aminotransferase (ALT), antioxidant enzymes [superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx)], extracellular signal-regulated kinase (ERK)1/2, p38 mitogen-activated protein kinase (MAPK), cyclo-oxygenase (COX-2), inducible nitric oxide synthetase (iNOS), and activator protein (AP-1) and the quantitative expressions of nuclear factor E2-related factor (Nrf2), heme oxygenase (HO-1), metallothionein (MT) and reduced glutathione (GSH) in mercury-chloride-exposed (50 μM and 10 mg/kg body weight) primary cultured hepatocytes and ICR mice, using biochemical assays, radioactivity and immunoblot analysis. The results demonstrated that ZPDC glycoprotein decreased the levels of LDH, ALT, HO-1 and MT, whereas it increased the activities of hepatic antioxidant enzymes (SOD, CAT and GPx) and reduced GSH in mercury-chloride-exposed primary cultured hepatocytes. Also, it suppressed arachidonic acid release and expression of ERK, p38 MAPK, COX-2, iNOS, AP-1 and Nrf-2 in primary cultured hepatocytes and ICR mice exposed to mercury chloride. Collectively, ZPDC glycoprotein may have potential applications to prevent hepatotoxicity induced by mercury chloride.
authors.affiliation: Molecular Biochemistry Laboratory, Biotechnology Research Institute & Center for the Control of Animal Hazards Using Biotechnology (BK21), Chonnam National University, Gwang-ju, Korea.
authors.forename: Jin
authors.initials: J
authors.lastname: Lee
authors.forename: Sei-Jung
authors.initials: SJ
authors.lastname: Lee
authors.forename: Kye-Taek
authors.initials: KT
authors.lastname: Lim
mesh_terms: D000410:Alanine Transaminase / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D016718:Arachidonic Acid / Q000096:biosynthesis; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D056486:Chemical and Drug Induced Liver Injury / Q000188:drug therapy* / Q000209:etiology / Q000517:prevention & control; D051546:Cyclooxygenase 2 / Q000378:metabolism; D004785:Environmental Pollutants / Q000633:toxicity*; D005260:Female; D005638:Fruit / Q000737:chemistry*; D022781:Hepatocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D008627:Mercuric Chloride / Q000633:toxicity*; D008813:Mice, Inbred ICR; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D010936:Plant Extracts / Q000737:chemistry / Q000627:therapeutic use; D010940:Plant Proteins / Q000494:pharmacology / Q000627:therapeutic use*; D061251:Primary Cell Culture; D018808:Transcription Factor AP-1 / Q000378:metabolism; D032106:Zanthoxylum / Q000737:chemistry*
chemical_list: D000975:Antioxidants; D004785:Environmental Pollutants; D010936:Plant Extracts; D010940:Plant Proteins; D018808:Transcription Factor AP-1; C000590033:ZPDC glycoprotein (24 kDa), Zanthoxylum; D016718:Arachidonic Acid; D008627:Mercuric Chloride; D007770:L-Lactate Dehydrogenase; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; D000410:Alanine Transaminase; D020928:Mitogen-Activated Protein Kinases
keywords: COX-2; ZPDC glycoprotein (24 kDa); arachidonic acid; mercury chloride (HgCl2)