Klingerman CM, Trushin N, Prokopczyk B, Haouzi P. H2S concentrations in the arterial blood during H2S administration in relation to its toxicity and effects on breathing. Am J Physiol Regul Integr Comp Physiol 305: R630 -R638, 2013. First published July 31, 2013; doi:10.1152/ajpregu.00218.2013.-Our aim was to establish in spontaneously breathing urethane-anesthetized rats, the relationship between the concentrations of H2S transported in the blood and the corresponding clinical manifestations, i.e., breathing stimulation and inhibition, during and following infusion of NaHS at increasing rates. The gaseous concentration of H2S (CgH2S, one-third of the total soluble form) was computed from the continuous determination of H2S partial pressure in the alveolar gas, while H2S, both dissolved and combined to hemoglobin, was measured at specific time points by sulfide complexation with monobromobimane (CMBBH2S). We found that using a potent reducing agent in vitro, H 2S added to the whole blood had little interaction with the plasma proteins, as sulfide appeared to be primarily combined and then oxidized by hemoglobin. In vivo, H 2S was undetectable in the blood in its soluble form in baseline conditions, while CMBBH 2S averaged 0.7 Ϯ 0.5 M. During NaHS infusion, H 2S was primarily present in nonsoluble form in the arterial blood: CMBBH 2S was about 50 times higher than CgH 2S at the lowest levels of exposure and 5 or 6 times at the levels wherein fatal apnea occurred. CgH 2S averaged only 1.1 Ϯ 0.7 M when breathing increased, corresponding to a CMBBH 2S of 11.1 Ϯ 5.4 M. Apnea occurred at CgH 2S above 5.1 M and CMBBH2S above 25.4 M. At the cessation of exposure, CMBBH 2S remained elevated, at about 3 times above baseline for at least 15 min. These data provide a frame of reference for studying the putative effects of endogenous H 2S and for testing antidotes against its deadly effects.

Electronic cigarette (EC) usage has increased exponentially, but limited data is available on its potential harmful effects. We tested for the presence of reactive, short-lived free radicals in EC aerosols by electron paramagnetic resonance spectroscopy (EPR) using the spin-trap phenyl-N-tert-butylnitrone (PBN). Radicals were detected in aerosols from all ECs and eliquids tested (2.5×1013 to 10.3×1013 radicals per puff at 3.3V) and from eliquid solvents propylene glycol and glycerol and from “dry puffing”. These results demonstrate, for the first time, the production of highly oxidizing free radicals from ECs which may present a potential toxicological risk to EC users.

DNA was isolated from tissues of F344 rats 24 h after treatment by s.c. injection with [5-3H]4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone ([5-3H]NNK) or [5-3H]N'-nitrosonornicotine ([5-3H]NNN). It was hydrolyzed with acid or at pH 7, 100 degrees C, and the hydrolysates were analyzed by HPLC. The major product in each case was identified as 4-hydroxy-1-(3-pyridyl)-1-butanone, formed by hydrolysis of a DNA adduct. It was detected in DNA from the livers of rats treated with [5-3H]NNK or [5-3H]NNN, and in DNA from lungs of rats treated with [5-3H]NNK. These results demonstrate that 4-(3-pyridyl)-4-oxobutylation of DNA occurs in rats treated with NNK or NNN, and are consistent with the hypothesis that these nitrosamines are metabolically activated by alpha-hydroxylation.