Neuroprotective Effects of Deuterium-Depleted Water (DDW) Against H2O2-Induced Oxidative Stress in Differentiated PC12 Cells Through the PI3K/Akt Signaling Pathway.

Oxidative stress plays an important role in the pathogenesis of neurodegenerative diseases, including Alzheimer's disease and Parkinson's disease. Induction of endogenous antioxidants to act against oxidative stress-mediated neuronal damage seems to be a reasonable strategy for delaying the progression of such diseases. In this study, we investigated the neuroprotective effect of deuterium-depleted water (DDW) against H2O2-induced oxidative stress in differentiated PC12 cells and the possible signaling pathways involved. The differentiated PC12 cell line was pretreated with DDW containing different concentrations (50-100 ppm) of deuterium and then treated with H2O2 to induce oxidative stress and neurotoxicity. We assessed cell survival, reactive oxygen species (ROS) generation, TUNEL assay, catalase (CAT), copper and zinc-containing superoxide dismutase (CuZn-SOD) and superoxide dismutase (SOD) activity and performed Western blot analysis to investigate the neuroprotective effect of DDW. The results indicated that DDW could attenuate H2O2-induced apoptosis, reduce ROS formation, and increase CAT, CuZn-SOD and SOD activity in H2O2-treated PC12 cells. Western blot analysis revealed that DDW treatment significantly increased the expression of p-Akt, Bcl-2 and GSK-3ß. However, the protective effect of DDW on cell survival and the DDW-mediated increases in p-Akt, Bcl-2 and GSK-3ß were abolished by pretreatment with the phosphatidylinositol-3-kinase (PI3K) inhibitor LY294002. In summary, DDW may protect differentiated PC12 cells against H2O2-induced oxidative stress through the PI3K/Akt signaling pathway.

Applications of ROS-InducedZr-MOFs Platform in Multimodal Synergistic Therapy.

BACKGROUND: Metal-organic frameworks (MOFs) possess adjustable aperture, high load capacities, tailorable structures, and excellent biocompatibilities for their use as drug delivery carries in cancer therapy. Until now, Zr-MOFs, in particular, combine optimal stability towards hydrolysis and post synthetic modification with low toxicity, and are widely studied for their excellentbiological performance. INTRODUCTION: This review comprises the exploration of Zr-MOFs as drug delivery devices (DDSs) with a focus on various new methods, including chemotherapy (CT), photodynamic therapy (PDT), photothermal therapy (PTT), sonodynamic therapy (SDT), radiotherapy, immunotherapy, gene therapy and related combined therapies, which all generate reactive oxygen species (ROS) to achieve high efficiency of tumor therapy. CONCLUSION: We described and summarized these pertinent examples of the therapeutic mechanisms and highlighted the antitumor effects of their biological application both in vitro and in vivo. The perspectives on their future applications and the analogous challenge of the Zr-MOFs materials are given.