Development and validation of a GC-MS/MS method for the determination of iodoacetic acid in biological samples.

Iodoacetic acid (IAA) is a halogenated disinfection by-product of growing concern due to its high cytotoxicity, genotoxicity, endocrine disruptor effects, and potential carcinogenicity. However, the data on distribution and excretion of IAA after ingestion by mammals are still scarce. Here, we developed a reliable and validated method for detecting IAA in biological specimens (plasma, urine, feces, liver, kidney, and tissues) based on modified QuEChERS sample preparation combined with gas chromatography-tandem triple quadrupole mass spectrometry (GC-MS/MS). The detection method for IAA exhibited satisfactory recovery rates (62.6-108.0%) with low relative standard deviations (RSD < 12.3%) and a low detection limit for all biological matrices ranging from 0.007 to 0.032 ng/g. The study showed that the proposed method was reliable and reproducible for analyzing IAA in biological specimens. It was successfully used to detect IAA levels in biological samples from rats given gavage administration. The results indicated that IAA was found in various tissues and organs, including plasma, thyroid, the liver, the kidney, the spleen, gastrointestinal tract, and others, 6 h after exposure. This study provides the first data on the in vivo distribution in and excretion of IAA by mammals following oral exposure.

Exogenous hydrogen sulfide donor NaHS alleviates nickel-induced epithelial-mesenchymal transition and the migration of A549 cells by regulating TGF-ß1/Smad2/Smad3 signaling.

Nickel compounds are known to be common environmental and occupational carcinogens which also promote the migration of lung cancer cells. However, the molecular mechanism yet remains to be clarified. Hydrogen sulfide (H2S) is involved in cancer biological processes. However, the exact effect and functionality of H2S on nickel, towards the promotion of the migration ability of lung cancer cells, remains to be unknown. In this study, we have found that the nickel chloride (NiCl2) treatment significantly downregulates the protein levels of endogenous H2S enzyme cystathionine ß-synthase (CBS), cystathionine γ-lyase (CSE) and 3-Mercaptopyruvate sulfurtransferase (3-MST). A correlation between NiCl2-induced epithelial-mesenchymal transition (EMT) and the migration ability of lung cancer A549 cells has been observed. Exogenous H2S donor, sodium hydrogen sulfide (NaHS) (100 µmol/L), can reverse NiCl2-induced EMT as well as the migration ability of A549 cells. NiCl2 treatment is able to upregulate the protein level of transforming growth factor-ß1 (TGF-ß1), p-Smad2, p-Smad3, p-JNK, p-ERK and p-P38 in a time-dependent fashion, indicating that both TGF-ß1/Smad2/Smad3 and mitogen-activated protein kinase (MAPK) signaling cascades (a non-Smad pathway) may play essential roles in NiCl2-dependent EMT as well as cell migration of human lung cancer cells. Furthermore, exogenous NaHS alleviates the NiCl2-induced EMT and the migration ability of A549 cells only by regulating TGF-ß1/Smad2/Smad3, rather than the MAPK, signaling pathway. These results indicate that the exogenous administration of NaHS might be a potential therapeutic strategy against nickel-induced lung cancer progression.