Dithiothreitol liberates non-acid labile sulfide from brain tissue of H2S-poisoned animals

Acid-labile sulfide measured by conventional gas dialysis and ion chromatography with electrochemical detection accounts for only a proportion of the total sulfide present in brain tissue after poisoning with NaHS, an H₂S precursor. Dithiothreitol (DTT) displaced additional measurable sulfide not detectable by the conventional techniques from NaHS-poisoned brain tissue. Sulfide liberation by DTT was dose-dependent and maximal at higher DTT concentration (10 and 30 mM) and was thought to represent non-acid labile sulfide. Dithiothreitol was also found to be significantly protective against H₂S poisoning. Furthermore, in vitro inhibition by sulfide of monoamine oxidase (MAO) was reversed by DTT, thus suggesting a molecular mechanism consistent with known persulfide chemistry. Persulfide formation may thus underlie some aspects of hydrogen sulfide neurotoxicity. The rational development of antidotes for use in H₂S poisoning may thus have to be centered on strategies concentrating on known thiol, disulfide and persulfide chemistry.