Monoamine oxidase inhibition as a sequel of hydrogen sulfide intoxication: increases in brain catecholamine and 5-hydroxytryptamine levels.
Administration of sodium hydrosulfide (NaHS), an alkali salt of hydrogen sulfide (H2S) at doses of 10 and 30 mg/kg, corresponding to sublethal and lethal doses (0.66 and 2.0 X LD50) resulted in significant increases in regional catecholamine levels of the rat brain only after the dose of 2.0 x LD50 of NaHS. Whereas the cortex and the cerebellum showed little or no change in catecholamine content, the hippocampus, striatum and brainstem all showed increases in noradrenaline and adrenaline. Additional analysis also showed that brainstem dopamine and 5-hydroxytryptamine levels (5-HT) increased as well. In vitro testing of sulfide for inhibition of monoamine oxidase (MAO) activity showed the anion to be inhibitory with an IC50 of 39.1 +/- 3.6 microM. Inhibition of MAO activity ex vivo could be demonstrated at a dose of 100 mg/kg but not at the lower dose of 30 mg/kg NaHS. Inhibition of enzyme activity could not be demonstrated at this lower dose, possibly due to the well known rapid intramitochondrial metabolism of sulfide. Correlation of synaptosomal and mitochondrial sulfide levels with enzyme inhibition data suggests that inhibition of MAO may be an important contributing factor to the mechanism(s) underlying loss of central respiratory drive after fatal intoxication with H2S.
Warenycia
M W
MW
Department of Pharmacology, University of Alberta, Edmonton, Canada.
Smith
K A
KA
Blashko
C S
CS
Kombian
S B
SB
Reiffenstein
R J
RJ
D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects*; D001933:Brain Stem / Q000378:metabolism; D002395:Catecholamines / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism; D004837:Epinephrine / Q000378:metabolism; D006862:Hydrogen Sulfide / Q000633:toxicity*; D007928:Lethal Dose 50; D008297:Male; D008928:Mitochondria / Q000378:metabolism; D008996:Monoamine Oxidase Inhibitors; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000378:metabolism*; D013574:Synaptosomes / Q000378:metabolism
D002395:Catecholamines; D008996:Monoamine Oxidase Inhibitors; D009419:Nerve Tissue Proteins; D012701:Serotonin; D004298:Dopamine; D009638:Norepinephrine; D004837:Epinephrine; D006862:Hydrogen Sulfide