title: Investigation of in vivo toxicity of hydroxylamine sulfate and the efficiency of intoxication treatment by α-tocopherol acetate and methylene blue.
abstract: OBJECTIVE
  Investigation of hydroxylamine sulfate toxicity mechanism in vivo and estimation of α-tocopherol acetate and methylene blue efficiency in poisoning treatments.
  
  
  METHODS
  In vivo experiments were conducted on 102 Wistar Han rats. The experiments investigated the hematotoxic and oxidative stress effects of hydroxylamine sulfate in acute and subacute toxicity treatment of animals. Electron Spin Resonance was used for quantitative determination of blood and liver tissue parameters alterations after intoxication. The osmotic fragility of erythrocytes, lipid peroxidation intensity and level of SH-groups in liver of rats were determined by established biochemical assays.
  
  
  RESULTS
  Hydroxylamine sulfate cause an acute hematotoxicity and oxidative stress in vivo as demonstrated by the appearance of free oxidized iron in blood, reduced glutathione content and increased lipid peroxidation in liver. The experimental studies showed the formation of Hb-NO, MetHb in erythrocytes and as well of stable complex of reduced iron (Fe(2+)) with hydroxylamine sulfate. Methylene blue treatment does not reduce the Hb-NO or MetHb levels in intoxicated animals while administration of α-tocopherol acetate reduces substantially lipid peroxidation.
  
  
  CONCLUSIONS
  Oxidative stress is a key mechanism of acute hematotoxicity caused by hydroxylamine sulfate. Methylene blue is not suitable antidote in case of hydroxylamine intoxication.
authors.affiliation: Ministry of Health, Institute of Ecohygiene and Toxicology, 6, Heroiv Oborony Str., UA-252022 Kiev, Ukraine. Electronic address: g.prodanchuk@ecohyntox.net.
authors.forename: Mykola G
authors.initials: MG
authors.lastname: Prodanchuk
authors.forename: Aristidis M
authors.initials: AM
authors.lastname: Tsatsakis
authors.forename: Georgiy M
authors.initials: GM
authors.lastname: Prodanchuk
authors.forename: Andreas K
authors.initials: AK
authors.lastname: Tsakalof
mesh_terms: D000818:Animals; D004578:Electron Spin Resonance Spectroscopy; D004912:Erythrocytes / Q000187:drug effects; D006898:Hydroxylamines / Q000506:poisoning / Q000633:toxicity*; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects; D008751:Methylene Blue / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects; D011041:Poisoning / Q000188:drug therapy*; D051381:Rats; D017208:Rats, Wistar; D012977:Sodium Nitrite / Q000506:poisoning; D023382:Toxicity Tests, Acute; D059551:Toxicity Tests, Subacute; D024502:alpha-Tocopherol / Q000494:pharmacology*
chemical_list: D006898:Hydroxylamines; D024502:alpha-Tocopherol; D012977:Sodium Nitrite; D008751:Methylene Blue
keywords: DTNB; ESR; Electron Spin Resonance; Ellman’s reagent 5,5′-dithiobis-(2-nitrobenzoic acid); HA; HAS; Hematotoxicity; Hydroxylamine sulfate; LPO; Mechanism of toxicity; MetHb; Methylene blue; Oxidative stress; TBARs assay; hydroxylamine; hydroxylamine sulfate; lipid peroxidation; methaemoglobin; thiobarbituric acid reactive substances assay; α-Tocopherol