Changes in intracellular pH play a secondary role in hydrogen sulfide-induced nasal cytotoxicity.

Hydrogen sulfide (H(2)S) is a naturally occurring gas that is also associated with several industries. The potential for widespread human inhalation exposure to this toxic gas is recognized as a public health concern. The nasal epithelium is particularly susceptible to H(2)S-induced pathology. Cytochrome oxidase inhibition is postulated as one mechanism of H(2)S toxicity. Another mechanism by which the weak acid H(2)S could cause nasal injury is intracellular acidification and cytotoxicity. To further understand the mechanism by which H(2)S damages the nasal epithelium, nasal respiratory and olfactory epithelial cell isolates and explants from naive rats were loaded with the pH-sensitive intracellular chromophore SNARF-1 and exposed to air or 10, 80, 200, or 400 ppm H(2)S for 90 min. Intracellular pH was measured using flow cytometry or confocal microscopy. Cell lysates were used to quantify total protein and cytochrome oxidase activity. A modest but statistically significant decrease in intracellular pH occurred following exposure of respiratory and olfactory epithelium to 400 ppm H(2)S. Decreased cytochrome oxidase activity was observed following exposure to >10 ppm H(2)S in both respiratory and olfactory epithelia. None of the treatments resulted in cytotoxicity. The intracellular acidification of nasal epithelial cells by high-dose H(2)S exposure and the inhibition of cytochrome oxidase at much lower H(2)S concentrations suggest that changes in intracellular pH play a secondary role in H(2)S-induced nasal injury.

Influence of dietary manganese on the pharmacokinetics of inhaled manganese sulfate in male CD rats.

Concerns exist as to whether individuals with relative manganese deficiency or excess may be at increased risk for manganese toxicity following inhalation exposure. The objective of this study was to determine whether manganese body burden influences the pharmacokinetics of inhaled manganese sulfate (MnSO(4)). Postnatal day (PND) 10 rats were placed on either a low (2 ppm), sufficient (10 ppm), or high (100 ppm) manganese diet. The feeding of the 2 ppm manganese diet was associated with a number of effects, including reduced body weight gain, decreased liver manganese concentrations, and reduced whole-body manganese clearance rates. Beginning on PND 77 +/- 2, male littermates were exposed 6 h/day for 14 consecutive days to 0, 0.092, or 0.92 mg MnSO(4)/m(3). End-of-exposure tissue manganese concentrations and whole-body (54)Mn elimination rates were determined. Male rats exposed to 0.092 mg MnSO(4)/m(3) had elevated lung manganese concentrations when compared to air-exposed male rats. Male rats exposed to 0.92 mg MnSO(4)/m(3) developed increased striatal, lung, and bile manganese concentrations when compared to air-exposed male rats. There were no significant interactions between the concentration of inhaled MnSO(4) and dietary manganese level on tissue manganese concentrations. Rats exposed to 0.92 mg MnSO(4)/m(3) also had increased (54)Mn clearance rates and shorter initial phase elimination half-lives when compared with air-exposed control rats. These results suggest that, marginally manganese-deficient animals exposed to high levels of inhaled manganese compensate by increasing biliary manganese excretion. Therefore, they do not appear to be at increased risk for elevated brain manganese concentrations.