title: Active oxygen species generation and cellular damage by additives of parenteral preparations: selenium and sulfhydryl compounds.
abstract: We investigated the relationship between active oxygen species (AOS) generation and cultured vascular endothelial cellular damage caused by simultaneous exposure to selenium compounds and sulfhydryl compounds such as cysteine (Cys) or reduced glutathione (GSH). Selenium compounds, selenite, selenate or selenomethionine (SeMet), are added to total parenteral nutrition (TPN) and intravenously administered. We confirmed by luminol dependent chemiluminescence, an indicator of AOS generation, that selenite generates AOS in the presence of clinical concentrations of sulfhydryl compounds, 0.5 mM Cys or 0.5 mM GSH, and that the amount of AOS generated reaches the maximum when their mole ratio is 1:50. However, AOS generation was not observed after simultaneous administration of various concentrations of selenate or SeMet with sulfhydryl compounds. Moreover, simultaneous exposure to 10 microM selenite and sulfhydryl compounds was found to result in significant increases in the [3H]-adenine and lactate dehydrogenase (LDH) release rates from cells, a significant decrease in the amount of cellular protein, and enhancement of cellular damage as compared with after exposure to selenite alone. However, simultaneous exposure to 10 microM selenate or 10 microM SeMet together with sulfhydryl compounds did not induce cellular damage. These findings revealed that selenite generates AOS and causes cellular damage in the presence of sulfhydryl compounds. Accordingly, it seems better to choose selenate or SeMet instead of selenite when a selenium compound is to be added to TPN.
authors.affiliation: Department of Pharmacy, St. Marianna University School of Medicine, Kawasaki, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Terada
authors.forename: M
authors.initials: M
authors.lastname: Yoshida
authors.forename: Y
authors.initials: Y
authors.lastname: Seko
authors.forename: T
authors.initials: T
authors.lastname: Kobayashi
authors.forename: K
authors.initials: K
authors.lastname: Yoshida
authors.forename: M
authors.initials: M
authors.lastname: Nakada
authors.forename: K
authors.initials: K
authors.lastname: Nakada
authors.forename: H
authors.initials: H
authors.lastname: Echizen
authors.forename: H
authors.initials: H
authors.lastname: Ogata
authors.forename: T
authors.initials: T
authors.lastname: Rikihisa
mesh_terms: D000225:Adenine / Q000378:metabolism; D002478:Cells, Cultured; D003545:Cysteine / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism*; D005978:Glutathione / Q000494:pharmacology; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008163:Luminescent Measurements; D010289:Parenteral Nutrition, Total; D011506:Proteins / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D064586:Selenic Acid; D012643:Selenium / Q000009:adverse effects* / Q000494:pharmacology; D018036:Selenium Compounds / Q000494:pharmacology; D012645:Selenomethionine / Q000494:pharmacology; D018038:Sodium Selenite / Q000494:pharmacology; D013438:Sulfhydryl Compounds / Q000009:adverse effects* / Q000494:pharmacology; D014471:Umbilical Veins
chemical_list: D011506:Proteins; D017382:Reactive Oxygen Species; D018036:Selenium Compounds; D013438:Sulfhydryl Compounds; D012645:Selenomethionine; D007770:L-Lactate Dehydrogenase; D005978:Glutathione; D012643:Selenium; D018038:Sodium Selenite; D064586:Selenic Acid; D000225:Adenine; D003545:Cysteine