Olfactory Mucosal Necrosis in Male CD Rats Following Acute Inhalation Exposure to Hydrogen Sulfide: Reversibility and the Possible Role of Regional Metabolism

Abstract

Hydrogen sulfide (H2S) is a potent inhibitor of cytochrome oxidase (CO) and is associated with dysosmia and anosmia in humans and nasal lesions in exposed rodents. An improved understanding of the pathogenesis of these lesions is needed to determine their toxicological relevance. We exposed 10-week-old male CD rats to 0, 30, 80, 200, or 400 ppm H2S for 3 hours/day for 1 or 5 days consecutively. The nose was histologically examined 24 hours after H2S exposure, and lesion recovery was assessed at 2 and 6 weeks following the 5-day exposure. A single 3-hour exposure to > or = 80 ppm H2S resulted in regeneration of the respiratory mucosa and full thickness necrosis of the olfactory mucosa localized to the ventral and dorsal meatus, respectively. Repeated exposure to the same concentrations caused necrosis of the olfactory mucosa with early mucosal regeneration that extended from the dorsal medial meatus to the caudal regions of the ethmoid recess. Acute exposure to 400 ppm H2S induced severe mitochondrial swelling in sustentacular cells and olfactory neurons, which progressed to olfactory epithelial necrosis and sloughing. CO immunoreactive cells were more frequently observed in regions of the olfactory mucosa commonly affected by H2S than in regions that were not. These findings demonstrate that acute exposure to >80 ppm H2S resulted in reversible lesions in the respiratory and olfactory mucosae of the CD rat and that CO immunoreactivity may be a susceptibility factor for H2S-induced olfactory toxicity in the rat.

Cystathionine γ-Lyase Overexpression Inhibits Cell Proliferation via a H2S-dependent Modulation of ERK1/2 Phosphorylation and p21Cip/WAK-1

“…H 2 S treatment has also been shown to lead to nasal lesions and olfactory epithelial necrosis (11). On the other hand, H 2 S induces serum-independent cell cycle entry in rat intestinal epithelial cells and increases the fraction of colonic mucosa cells in the S phase (12,13).…”

Olfactory Epithelial Lesions Induced by Various Cancer Chemotherapeutic Agents in Mice

“…Apoptosis in various tissues caused by antimicrotubule agents including VCR, vinblastine sulfate (VBL), vindesine sulfate (VDS), and paclitaxel (PTX) is a very complex process associated with many protein kinase signaling pathway, and it is supposed that phosphorylation of bcl-2 and elevations of p53 and p21 lead to apoptosis (Wang et al, 1999). In another aspect, the susceptibility of local tissues to xenobiotics has been reported to sometimes differ from site-to-site in the olfactory epithelium, and to be related to site-specific metabolism that can also play a crucial role in the tissue concentration of the parent compound or toxic metabolites (Morgan, 1994;Cleton, 1995;Brenneman et al, 2002).…”

Short-term effects of subchronic low-level hydrogen sulfide exposure on oil field workers

“…The previous experimental studies on rats and human revealed a role of H 2 S on the living cells. A study on experimental rats, H 2 S inhalation was found to have a severe cytotoxic effect on the nasal epithelium [6] and olfactory epithelial necrosis and sloughing [7]. In human studies, H 2 S was also found to have a dose-dependent intensification of cell death via apoptosis and necrosis [11].…”

“…The same mechanism may cause pharyngeal soreness, gingivitis, rhinitis, and eyes irritation. On chronic exposure, this also might cause gingival and periodontal disease among people who work in environment with presence of H 2 S. Acute, subchronic, and prolong exposure to H 2 S might also cause neuronal olfactory damage, loss of smell sensation, and rhinitis which was reported in previous studies on human, rats, and mice [4,7,14,15]. At lower concentrations, H 2 S was found to cause eye mucosal irritation, and keratoconjunctivitis called 'gas eye', and at higher concentrations there was risk of pulmonary edema [16].…”

“…H 2 S odor was strongly associated with reports of alteration of daily activities, negative mood states, mucosal irritation, and upper respiratory symptoms [5]. It was also concluded by experiment on rats that inhalation of H 2 S had a severe cytotoxic effect on the nasal epithelium and a severe edematogenic effect on lung parenchyma [6] whereas acute exposure to 400 ppm H 2 S induced severe mitochondrial swelling in support cells and olfactory neurons, which progressed to olfactory epithelial necrosis and sloughing [7]. On the other hand, subchronic exposure of rats to 30 or 80 ppm H 2 S results in olfactory neuron loss and basal cell hyperplasia [1].…”