title: Neuronal effects of 4-t-Butylcatechol: a model for catechol-containing antioxidants.
abstract: Many herbal medicines and dietary supplements sold as aids to improve memory or treat neurodegenerative diseases or have other favorable effects on the CNS contain a catechol or similar 1,2-dihydroxy aromatic moiety in their structure. As an approach to isolate and examine the neuroprotective properties of catechols, a simple catechol 4-t-Butylcatechol (TBC) has been used as a model. In this study, we investigated the effects of TBC on lipopolysaccharide (LPS)-activated microglial-induced neurotoxicity by using the in vitro model of coculture murine microglial-like cell line HAPI with the neuronal-like human neuroblastoma cell line SH-SY5Y. We also examined the effects of TBC on 6-hydroxydopamine (6-OHDA)-induced neurotoxicity in human dopaminergic neuroblastoma SH-SY5Y cells. TBC at concentrations from 0.1-10 microM had no toxic effect on HAPI cells and SH-SY5Y cells, and it inhibited LPS (100 ng/ml)-induced increases of superoxide, intracellular ROS, gp91(Phox), iNOS and a decrease of HO-1 in HAPI cells. Under coculture condition, TBC significantly reduced LPS-activated microglia-induced dopaminergic SH-SY5Y cells death. Moreover, TBC (0.1-10 microM) inhibited 6-OHDA-induced increases of intracellular ROS, iNOS, nNOS, and a decrease of mitochondria membrane potential, and cell death in SH-SY5Y cells. However, the neurotoxic effects of TBC (100 microM) on SH-SY5Y cells were also observed including the decrease in mitochondria membrane potential and the increase in COX-2 expression and cell death. TBC-induced SH-SY5Y cell death was attenuated by pretreatment with NS-398, a selective COX-2 inhibitor. In conclusion, this study suggests that TBC might possess protective effects on inflammation- and oxidative stress-related neurodegenerative disorders. However, the high concentration of TBC might be toxic, at least in part, for increasing COX-2 expression.
authors.affiliation: Department of Pharmacology and Graduate Institute of Pharmacology, Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan. yichlo@kmu.edu.tw
authors.forename: Yi-Ching
authors.initials: YC
authors.lastname: Lo
authors.forename: Yuxin
authors.initials: Y
authors.lastname: Liu
authors.forename: Yi-Chin
authors.initials: YC
authors.lastname: Lin
authors.forename: Yu-Tzu
authors.initials: YT
authors.lastname: Shih
authors.forename: Chi-Ming
authors.initials: CM
authors.lastname: Liu
authors.forename: Leo T
authors.initials: LT
authors.lastname: Burka
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002396:Catechols / Q000494:pharmacology*; D002460:Cell Line; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D018920:Coculture Techniques; D051546:Cyclooxygenase 2 / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D051547:Heme Oxygenase-1 / Q000378:metabolism; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D008562:Membrane Glycoproteins / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D017628:Microglia / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D052248:Nitric Oxide Synthase Type I / Q000037:antagonists & inhibitors / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors / Q000378:metabolism; D009578:Nitrobenzenes / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects; D016627:Oxidopamine / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013449:Sulfonamides / Q000494:pharmacology
chemical_list: D000975:Antioxidants; D002396:Catechols; D016861:Cyclooxygenase Inhibitors; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D009578:Nitrobenzenes; D017382:Reactive Oxygen Species; D013449:Sulfonamides; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; C038096:tert-butylcatechol; D016627:Oxidopamine; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; C496541:HMOX1 protein, human; D051547:Heme Oxygenase-1; D051546:Cyclooxygenase 2; C500593:Cybb protein, rat; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases