Self-poisoning by sodium nitrite ingestion: Investigating toxicological mechanisms in vitro

Abstract

Nitrite ingestion has recently emerged as a suicidal method. The mechanisms of toxicity involved in fatal intoxications are associated with the disturbance of physiological processes, mainly through the massive induction of methemoglobinemia. However, there is limited information on the whole spectrum of effects following acute poisonings, requiring additional investigation. An in vitro study of sodium nitrite/nitrate toxicity (25–400 mM, 4 h) was conducted to assess the direct effect on cell models (H9c2, Caco-2 and SH-SY5Y). Cell viability assays (neutral red uptake and MTT reduction) were performed to obtain full concentration-toxicity curves. In vitro digestion assays were also conducted to study potential transformations of nitrite (2.6 g) into other chemical species within the gastrointestinal tract. Additionally, the blood levels of sodium nitrite/nitrate (1–500 mM, 20 min) associated with the increase of methemoglobin in human blood samples were evaluated using a spectrophotometric technique. Cell viability assays showed no significant toxicity of sodium nitrite or nitrate for any of the tested cell lines at biologically relevant concentrations, even those found in intoxication cases. Digestion simulation tests revealed that nitrite is likely to convert into other nitrogen species, especially in the gastric environment. In vitro exposure of blood to sodium nitrite resulted in the production of methemoglobin, whereas nitrate did not exhibit the same effect. The data suggest that methemoglobinemia is the primary mechanism of toxicity in nitrite poisonings. Nevertheless, further research is needed to better understand the progression of these episodes, which could help refine treatment strategies.