TOF-SIMS imaging of halide/thiocyanate anions and hydrogen sulfide in mouse kidney sections using silver-deposited plates

In vivo imaging of reactive small molecule metabolites with high spatial resolution and specificity could give clues to understanding pathophysiology of various diseases. We herein applied time of flight-secondary ion mass spectrometry (TOF-SIMS) to newly developed silverdeposited plates that were stamped on mouse tissues, and succeeded in visualization of halide (Cl-, Br-, and I-) and pseudohalide thiocyanate (SCN-) anions, a class of substrates for neutrophils/eosinophil peroxidases to produce hypohalous acids (HOX/OX- mixture; X: (pseudo) halides) , as well as hydrogen sulfide (H2S) . Forty-micrometer frozen mouse kidney sections on cover glasses were attached to 37 °C preheated silver-deposited plates and incubated at -10 °C for 1 h. After sputter cleaning to remove surface contaminants, the plates were analyzed by TOF-SIMS to identify distribution of Br-, AgBr ₂-, I-, AgI ₂ -, SCN-, as well as S ^2- and AgS- as products of tissue-derived H ₂S. Br-, AgBr ₂ -, I-, and SCN- anions were mainly distributed in core regions including the inner medulla and inner stripe of the outer medulla (except for I-) , rather than outer regions such as the cortex and outer stripe of the outer medulla. AgI ₂ - anion was spread over the whole kidney, although its levels were relatively low. In contrast, S ^2- and AgS- anions were mainly present in the outer regions. To our knowledge, this is the first imaging study to reveal the distribution of (pseudo) halides and H ₂S in animal tissue sections.