title: Therapeutic concentration of morphine reduces oxidative stress in glioma cell line.
abstract: Morphine is a potent analgesic opioid used extensively for pain treatment. During the last decade, global consumption grew more than 4-fold. However, molecular mechanisms elicited by morphine are not totally understood. Thus, a growing literature indicates that there are additional actions to the analgesic effect. Previous studies about morphine and oxidative stress are controversial and used concentrations outside the range of clinical practice. Therefore, in this study, we hypothesized that a therapeutic concentration of morphine (1 μM) would show a protective effect in a traditional model of oxidative stress. We exposed the C6 glioma cell line to hydrogen peroxide (H2O2) and/or morphine for 24 h and evaluated cell viability, lipid peroxidation, and levels of sulfhydryl groups (an indicator of the redox state of the cell). Morphine did not prevent the decrease in cell viability provoked by H2O2 but partially prevented lipid peroxidation caused by 0.0025% H2O2 (a concentration allowing more than 90% cell viability). Interestingly, this opioid did not alter the increased levels of sulfhydryl groups produced by exposure to 0.0025% H2O2, opening the possibility that alternative molecular mechanisms (a direct scavenging activity or the inhibition of NAPDH oxidase) may explain the protective effect registered in the lipid peroxidation assay. Our results demonstrate, for the first time, that morphine in usual analgesic doses may contribute to minimizing oxidative stress in cells of glial origin. This study supports the importance of employing concentrations similar to those used in clinical practice for a better approximation between experimental models and the clinical setting.
authors.affiliation: Laboratório de Farmacologia Molecular, Instituto de Ciências Biológicas, Universidade Federal do Pará, Belém, PA, Brasil.
authors.forename: M B
authors.initials: MB
authors.lastname: Almeida
authors.affiliation: Laboratório de Farmacologia Molecular, Instituto de Ciências Biológicas, Universidade Federal do Pará, Belém, PA, Brasil.
authors.forename: A
authors.initials: A
authors.lastname: Costa-Malaquias
authors.affiliation: Laboratório de Neuroquímica Molecular e Celular, Instituto de Ciências Biológicas, Universidade Federal do Pará, Belém, PA, Brasil.
authors.forename: J L M
authors.initials: JL
authors.lastname: Nascimento
authors.affiliation: Laboratório de Neuroendocrinologia, Instituto de Ciências Biológicas, Universidade Federal do Pará, Belém, PA, Brasil.
authors.forename: K R
authors.initials: KR
authors.lastname: Oliveira
authors.affiliation: Laboratório de Neuroendocrinologia, Instituto de Ciências Biológicas, Universidade Federal do Pará, Belém, PA, Brasil.
authors.forename: A M
authors.initials: AM
authors.lastname: Herculano
authors.affiliation: Laboratório de Farmacologia Molecular, Instituto de Ciências Biológicas, Universidade Federal do Pará, Belém, PA, Brasil.
authors.forename: M E
authors.initials: ME
authors.lastname: Crespo-López
mesh_terms: D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D045744:Cell Line, Tumor; D002470:Cell Survival; D016166:Free Radical Scavengers / Q000494:pharmacology; D005910:Glioma / Q000188:drug therapy* / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000008:administration & dosage*; D015227:Lipid Peroxidation / Q000187:drug effects; D008954:Models, Biological; D009020:Morphine / Q000008:administration & dosage / Q000494:pharmacology*; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects*; D065840:Protective Factors; D051381:Rats; D013438:Sulfhydryl Compounds / Q000032:analysis
chemical_list: D000701:Analgesics, Opioid; D016166:Free Radical Scavengers; D013438:Sulfhydryl Compounds; D009020:Morphine; D006861:Hydrogen Peroxide
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