Hydrogen Sulfide Specifically Alters NAD(P)H Quinone Dehydrogenase 1 (NQO1) Olfactory Neurons in the Rat

Abstract

The regions of the olfactory epithelium affected by hydrogen sulfide (H2S) toxicity in the rat present a striking similarity with the developmental olfactory zone 1 described in the mouse. This zone which is the only region containing neurons expressing NAD(P)H quinone dehydrogenase 1 (NQO1) is involved in complex behavioral responses in rodents, and other mammals, triggered by specific olfactory stimuli. We therefore sought to determine whether 1) olfactory neurons expressing NQO1 are located in the same regions in the rats and in the mice and 2) there is an overlap between olfactory neurons expressing this protein and those affected by the toxicity of H2S. Rats were exposed to H2S – 200 ppm during 3 hours, 3 consecutive days- and displayed symmetric acute segmental necrosis of the neurons and sustentacular cells of the olfactory epithelium in the dorsomedial nasal cavity. We found that expression of NQO1 in Sprague-Dawley rats spatially recapitulated that of the mouse. The degree of agreement or overlap between these 2 populations of neurons (necrosis vs. NQO1 expression) reached 80.2 %. Although the underlying mechanisms accounted for the high sensitivity for NQO1 neurons -or the relative protection of non NQO1 neurons- to sulfide toxicity remain to be established, this observation is offering an intriguing approach that could be used to acutely suppress the pool of neural cells in olfactory zone I and to understand the mechanisms of toxicity and protection of other populations of neurons exposed to sulfide.

Intramuscular aminotetrazole cobinamide as a treatment for inhaled hydrogen sulfide poisoning in a large swine model

“…However, we used intravenous rather than inhaled anesthesia to reduce pulmonary effects and interactions with H 2 S gas and we used the same anesthesia protocol in control and treated animals. Fourth, the animals were intubated, bypassing the olfactory epithelium and sensory neurons, which are a target of H 2 S. 18 The olfactory epithelium contains a rich capillary network and lies below the cribriform plate. Olfactory cells in the cribriform plate extend into the cranial cavity, thus allowing absorption into the cerebral spinal fluid and absorption across the blood-brain barrier.…”

“…[13][14][15][16][17] Although H 2 S has a potent "rotten egg" odor, olfactory fatigue occurs quickly, resulting in people being unaware they are being exposed to the gas. 18 H 2 S is easily made by combining readily available chemicals that contain an acid (i.e., disinfectants) with those that contain sulfur (i.e., pesticides), and is used frequently as a suicidal agent. 5,6 Because H 2 S is easy to make and has a high risk of lethality, several governmental agencies, including the U.S. Department of Homeland Security, have recognized its potential as a chemical threat agent.…”

“…Additionally, inhibition of L‐type calcium channels in the heart can cause pulseless electrical activity 13–17 . Although H 2 S has a potent “rotten egg” odor, olfactory fatigue occurs quickly, resulting in people being unaware they are being exposed to the gas 18 …”

Use of Nasal Pathology in the Derivation of Inhalation Toxicity Values for Hydrogen Sulfide

“…The NQO1 reduces quinones and may lower cellular production of free radical and toxic oxygen metabolite. 12 The toxicologic significance of this finding with respect to nasal toxicity of H 2 S remains unknown. Short-term inhalation studies in rats using microarray analysis of tissues collected from affected sites show that H 2 S alters expression of genes associated with a variety of biological processes including cell cycle regulation, protein kinase regulation, and cytoskeletal organization and biogenesis.…”

“…The H 2 S-induced effects on the olfactory mucosa have been replicated in other short-term rodent inhalation studies. 12,13 Inamura and coworkers 12 reported that rat olfactory neurons affected by H 2 S inhalation express NAD(P)H quinone dehydrogenase 1 (NQO1). The NQO1 reduces quinones and may lower cellular production of free radical and toxic oxygen metabolite.…”