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Fabry disease (FD) is a lysosomal disorder caused by mutations leading to a deficient activity α-galactosidase A with progressive and systemic accumulation of its substrates. Substrates deposition is related to tissue damage in FD, but the underlying molecular mechanisms remain not completely understood. DNA damage has been associated with disease progression in chronic diseases and was recently described in high levels in Fabry patients. Once renal complications are major morbidity causes in FD, we investigated the effects of the latest biomarker for FD - globotriaosylsphingosine (lyso-Gb3) in a cultured renal lineage - human embryonic kidney cells (HEK-293 T) - on DNA damage. In concentrations found in Fabry patients, lyso-Gb3 induced DNA damage (by alkaline comet assay) with oxidative origin in purines and pyrimidines (by comet assay with endonucleases). These data provide new information about a deleterious effect of lyso-Gb3 and could be useful to studies looking for new therapeutic strategies to FD.

Diabetes is a chronic metabolic disease associated with oxidative stress, damage to biomolecules such as DNA, and neuroinflammation. Taurine, a sulfur-containing amino acid widespread in the brain, has neuroprotective properties that might prevent tissue injury and DNA damage induced by chronic hyperglycemia. We evaluated the effects of chronic taurine treatment on oxidative stress parameters, DNA damage and inflammatory markers in the frontal cortex, and hippocampus of streptozotocin-induced diabetic rats. Diabetic rats displayed increased levels of reactive oxygen species (ROS) and DNA damage in both areas, evidencing the pro-oxidant effects of diabetes in the brain. Moreover, this condition increased levels of several inflammatory mediators, such as IL-6, IL-12, TNF-γ, and IFN-α, more pronouncedly in the hippocampus. Supporting our hypothesis, taurine treatment reduced ROS, DNA damage, and inflammatory cytokine levels, providing evidence of its beneficial effects against genotoxicity and neuroinflammation associated with diabetes. Our data endorse the necessary clinical trials to evaluate the efficacy and safety of taurine supplementation in the prevention and treatment of neurochemical and metabolic alterations related to diabetes.

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This work describes the synthesis of photoactive proton transfer compounds based on the benzazolic core containing the azide group. The compounds present absorption in the UV region and fluorescence emission in the visible region of the spectra with large Stokes shift due to a phototautomerism in the excited state (ESIPT). The azide location on the benzazolic structure presented a noteworthy role on their photophysics, leading to fluorescence quenching. A photophysical study was performed in the presence of NaHS to evaluate their application as an H 2 S sensor. The methodology employed was the reduction of azides to amines using NaHS to mimic H 2 S, resulting in an off−on response fluorescence mechanism. The observed photophysical features were successfully used to explore the azides as fluorescent probes in biological media. In addition, DFT and TD-DFT calculations with the CAM-B3LYP/cc-pVDZ and CAM-B3LYP/jun-cc-pVTZ level, respectively, were performed in order to understand the photophysics features of azide derivatives, where the main interest was to investigate the fluorescence quenching experimentally observed in the azide derivatives.

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