Investigation of in vivo toxicity of hydroxylamine sulfate and the efficiency of intoxication treatment by alpha-tocopherol acetate and methylene blue

Abstract

Objectives: Investigation of hydroxylamine sulfate toxicity mechanism in vivo and estimation of alpha-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 (Fe2+) with hydroxylamine sulfate. Methylene blue treatment does not reduce the Hb-NO or MetHb levels in intoxicated animals while administration of alpha-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. (C) 2013 Elsevier Ltd. All rights reserved.