Effects of Nutraceuticals on Cisplatin-Induced Cytotoxicity in HEI-OC1 Cells.

Cisplatin is a chemotherapeutic drug for the treatment of several solid tumors, whose use is limited by its nephrotoxicity, neurotoxicity, ototoxicity, and development of resistance. The toxicity is caused by DNA cross-linking, increase in reactive oxygen species and/or depletion of cell antioxidant defenses. The aim of the work was to study the effect of antioxidant compounds (Lisosan G, Taurisolo®) or hydrogen sulfide (H2S)-releasing compounds (erucin) in the auditory HEI-OC1 cell line treated with cisplatin. Cell viability was determined using the MTT assay. Caspase and sphingomyelinase activities were measured by fluorometric and colorimetric methods, respectively. Expression of transcription factors, apoptosis hallmarks and genes codifying for antioxidant response proteins were measured by Western blot and/or RT-qPCR. Lisosan G, Taurisolo® and erucin did not show protective effects. Sodium hydrosulfide (NaHS), a donor of H2S, increased the viability of cisplatin-treated cells and the transcription of heme oxygenase 1, superoxide dismutase 2, NAD(P)H quinone dehydrogenase type 1 and the catalytic subunit of glutamate-cysteine ligase and decreased reactive oxygen species (ROS), the Bax/Bcl2 ratio, caspase-3, caspase-8 and acid sphingomyelinase activity. Therefore, NaHS might counteract the cytotoxic effect of cisplatin by increasing the antioxidant response and by reducing ROS levels and caspase and acid sphingomyelinase activity.

Assessment of Sourdough Fermentation Impact on the Antioxidant and Anti-Inflammatory Potential of Pearl Millet from Burkina Faso.

Millet, a gluten-free cereal, has received attention for its environmental friendliness and higher protein content than other grains. It represents a staple food in many African countries, where fermentation is traditionally used for preserving food products and preparing different cereal-based products. This study aimed to assess the impact of sourdough fermentation on bioactive compounds and antioxidant and anti-inflammatory properties of pearl millet from Burkina Faso. Phenolic compounds were investigated spectrophotometrically and by HPLC-DAD. The antioxidant activity of unfermented (MF) and fermented (FeMF) millet was evaluated in vitro by spectrophotometric and fluorometric assays and ex vivo on oxidized human erythrocytes for hemolysis inhibition. Finally, the potential anti-inflammatory effect of FeMF and MF was evaluated on human adenocarcinoma cell line (HT-29) exposed to TNF-α inflammatory stimulus. Results revealed significantly higher levels of polyphenols, flavonoids, and in vitro antioxidant activity following millet fermentation. Notable differences in phenolic composition between FeMF and MF are observed, with fermentation facilitating the release of bioactive compounds such as gallic acid, quercetin, and rutin. A dose-dependent protection against oxidative hemolysis was observed in both FeMF- and MF-pretreated erythrocytes. Similarly, pretreatment with FeMF significantly reduced the levels of inflammatory markers in TNF-α-treated cells, with effects comparable to those of MF. Fermentation with sourdough represents a simple and low-cost method to improve the bioactive compounds content and in vitro antioxidant activity of millet flour with promising nutraceutical potential.

Pegylated-liposomes increase the efficacy of Idelalisib in lymphoma B-cells.

New drugs and technologies are continuously developed to improve the efficacy and minimize the critical side effects of cancer treatments. The present investigation focuses on the development of a liposomal formulation for Idelalisib, a small-molecule kinase inhibitor approved for the treatment of lymphoid malignancies. Idelalisib is a potent and selective antitumor agent, but it is not indicated nor recommended for first-line treatment due to fatal and serious toxicities. Herein, liposomes are proposed as a delivery tool to improve the therapeutic profile of Idelalisib. Specifically, PEGylated liposomes were prepared, and their physicochemical and technological features were investigated. Light-scattering spectroscopy and cryo-transmission electron microscopy revealed nanosized unilamellar vesicles, which were proved to be stable in storage and in simulated biological fluids. The cytotoxicity of the liposome formulation was investigated in a human non-Hodgkin's lymphoma B cell line. Idelalisib was able to induce death of tumor cells if delivered by the nanocarrier system at increased efficacy. These findings suggest that combining Idelalisib and nanotechnologies may be a powerful strategy to increase the antitumor efficacy of the drug.