title: Protective effect of dieckol against chemical hypoxia-induced cytotoxicity in primary cultured mouse hepatocytes.
abstract: Hepatic ischemic injury is a major complication arising from liver surgery, transplantation, or other ischemic diseases, and both reactive oxygen species (ROS) and pro-inflammatory mediators play the role of key mediators in hepatic ischemic injury. In this study, we examined the effect of dieckol in chemical hypoxia-induced injury in mouse hepatocytes. Cell viability was significantly decreased after treatment with cobalt chloride (CoCl2), a well-known hypoxia mimetic agent in a time- and dose-dependent manner. Pretreatment with dieckol before exposure to CoCl2 significantly attenuated the CoCl2-induced decrease of cell viability. Additionally, pretreatment with dieckol potentiated the CoCl2-induced decrease of Bcl-2 expression and attenuated the CoCl2-induced increase in the expression of Bax and caspase-3. Treatment with CoCl2 resulted in an increased intracellular ROS generation, which is inhibited by dieckol or N-acetyl cysteine (NAC, a ROS scavenger), and p38 MAPK phosphorylation, which is also blocked by dieckol or NAC. In addition, dieckol and SB203580 (p38 MAPK inhibitor) increased the CoCl2-induced decrease of Bcl-2 expression and decreased the CoCl2-induced increase of Bax and caspase-3 expressions. CoCl2-induced decrease of cell viability was attenuated by pretreatment with dieckol, NAC, and SB203580. Furthermore, dieckol attenuated CoCl2-induced COX-2 expression. Similar to the effect of dieckol, NAC also blocked CoCl2-induced COX-2 expression. Additionally, CoCl2-induced decrease of cell viability was attenuated not only by dieckol and NAC but also by NS-398 (a selective COX-2 inhibitor). In conclusion, dieckol protects primary cultured mouse hepatocytes against CoCl2-induced cell injury through inhibition of ROS-activated p38 MAPK and COX-2 pathway.
authors.affiliation: Department of Molecular Physiology, College of Pharmacy, Kyungpook National University , Daegu , Korea .
authors.forename: Yu Jin
authors.initials: YJ
authors.lastname: Jeon
authors.forename: Hyoung Seok
authors.initials: HS
authors.lastname: Kim
authors.forename: Kyung-Sik
authors.initials: KS
authors.lastname: Song
authors.forename: Ho Jae
authors.initials: HJ
authors.lastname: Han
authors.forename: Soo Hyun
authors.initials: SH
authors.lastname: Park
authors.forename: Woochul
authors.initials: W
authors.lastname: Chang
authors.forename: Min Young
authors.initials: MY
authors.lastname: Lee
mesh_terms: D000818:Animals; D001572:Benzofurans / Q000494:pharmacology*; D015687:Cell Hypoxia / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects*; D002478:Cells, Cultured; D003035:Cobalt / Q000008:administration & dosage / Q000633:toxicity; D051546:Cyclooxygenase 2 / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D022781:Hepatocytes / Q000187:drug effects* / Q000473:pathology; D007093:Imidazoles / Q000494:pharmacology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009578:Nitrobenzenes / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism; D013449:Sulfonamides / Q000494:pharmacology; D013997:Time Factors; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D001572:Benzofurans; D007093:Imidazoles; D009578:Nitrobenzenes; D011725:Pyridines; D017382:Reactive Oxygen Species; D013449:Sulfonamides; C503840:dieckol; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; D003035:Cobalt; D051546:Cyclooxygenase 2; D048051:p38 Mitogen-Activated Protein Kinases; C018021:cobaltous chloride; C093642:SB 203580
keywords: Cobalt chloride; dieckol; hypoxic cell injury; mouse hepatocytes; reactive oxygen species