Hydrogen sulfide intoxication induced brain injury and methylene blue.

Hydrogen sulfide (H2S) remains a chemical hazard in the gas and farming industry. It is easy to manufacture from common chemicals and thus represents a potential threat for the civilian population. It is also employed as a method of suicide, for which incidence has recently increased in the US. H2S is a mitochondrial poison and exerts its toxicity through mechanisms that are thought to result from its high affinity to various metallo-proteins (such as - but not exclusively- the mitochondrial cytochrome c oxidase) and interactions with cysteine residues of proteins. Ion channels with critical implications for the cardiac and the brain functions appear to be affected very early during and following H2S exposure, an effect which is rapidly reversible during a light intoxication. However, during severe H2S intoxication, a coma, associated with a reduction in cardiac contractility, develops within minutes or even seconds leading to death by complete electro-mechanical dissociation of the heart. If the level of intoxication is milder, a rapid and spontaneous recovery of the coma occurs as soon as the exposure stops. The risk, although probably very small, of developing long-term debilitating motor or cognitive deficits is present. One of the major challenges impeding our effort to offer an effective treatment against H2S intoxication after exposure is that the pool of free/soluble H2S almost immediately disappears from the body preventing agents trapping free H2S (cobalt or ferric compounds) to play their protective role. This paper (1) presents and discusses the neurological symptoms and lesions observed in various animals models and in humans following an acute exposure to sub-lethal or lethal levels of H2S, (2) reviews the potential interest of methylene blue (MB), a potent cyclic redox dye - currently used for the treatment of methemoglobinemia - which has potential rescuing effects on the mitochondrial activity, as an antidote against sulfide intoxication.