title: Non-specific inhibition of ischemia- and acidosis-induced intracellular calcium elevations and membrane currents by α-phenyl-N-tert-butylnitrone, butylated hydroxytoluene and trolox.
abstract: Ischemia, and subsequent acidosis, induces neuronal death following brain injury. Oxidative stress is believed to be a key component of this neuronal degeneration. Acute chemical ischemia (azide in the absence of external glucose) and acidosis (external media buffered to pH 6.0) produce increases in intracellular calcium concentration ([Ca2+]i) and inward membrane currents in cultured rat cortical neurons. Two α-tocopherol analogues, trolox and butylated hydroxytoluene (BHT), and the spin trapping molecule α-Phenyl-N-tert-butylnitrone (PBN) were used to determine the role of free radicals in these responses. PBN and BHT inhibited the initial transient increases in [Ca2+]i, produced by ischemia, acidosis and acidic ischemia and increased steady state levels in response to acidosis and the acidic ischemia. BHT and PBN also potentiated the rate at which [Ca2+]i increased after the initial transients during acidic ischemia. Trolox inhibited peak and sustained increases in [Ca2+]i during ischemia. BHT inhibited ischemia induced initial inward currents and trolox inhibited initial inward currents activated by acidosis and acidic ischemia. Given the inconsistent results obtained using these antioxidants, it is unlikely their effects were due to elimination of free radicals. Instead, it appears these compounds have non-specific effects on the ion channels and exchangers responsible for these responses.
authors.affiliation: Department of Molecular Pharmacology and Physiology, University of South Florida, College of Medicine, 12901 Bruce B. Downs Blvd., MDC-9, Tampa, FL 33612, USA. ckatnik@health.usf.edu.
authors.forename: Christopher
authors.initials: C
authors.lastname: Katnik
authors.affiliation: Department of Molecular Pharmacology and Physiology, University of South Florida, College of Medicine, 12901 Bruce B. Downs Blvd., MDC-9, Tampa, FL 33612, USA. jcuevas@health.usf.edu.
authors.forename: Javier
authors.initials: J
authors.lastname: Cuevas
mesh_terms: D000143:Acids / Q000494:pharmacology*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001386:Azides / Q000494:pharmacology*; D002084:Butylated Hydroxytoluene / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000196:embryology; D002839:Chromans / Q000494:pharmacology*; D003497:Cyclic N-Oxides / Q000494:pharmacology*; D005470:Fluorometry; D016257:Fura-2 / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D051381:Rats
chemical_list: D000143:Acids; D000975:Antioxidants; D001386:Azides; D002839:Chromans; D003497:Cyclic N-Oxides; D002084:Butylated Hydroxytoluene; C029217:phenyl-N-tert-butylnitrone; C010643:6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid; D002118:Calcium; D016257:Fura-2