MitoQ is a mitochondria-targeted derivative of the antioxidant ubiquinone, with antioxidant and anti-apoptotic functions. Reactive oxygen species are involved in many inflammatory diseases including ...inflammatory bowel disease. In this study, we assessed the therapeutic effects of MitoQ in a mouse model of experimental colitis and investigated the possible mechanisms underlying its effects on intestinal inflammation.
Reactive oxygen species levels and mitochondrial function were measured in blood mononuclear cells of patients with inflammatory bowel disease. The effects of MitoQ were evaluated in a dextran sulfate sodium-induced colitis mouse model. Clinical and pathological markers of disease severity and oxidative injury, and levels of inflammatory cytokines in mouse colonic tissue were measured. The effect of MitoQ on inflammatory cytokines released in the human macrophage-like cell line THP-1 was also analyzed.
Cellular and mitochondrial reactive oxygen species levels in mononuclear cells were significantly higher in patients with inflammatory bowel disease (P <0.003, cellular reactive oxygen species; P <0.001, mitochondrial reactive oxygen species). MitoQ significantly ameliorated colitis in the dextran sulfate sodium-induced mouse model in vivo, reduced the increased oxidative stress response (malondialdehyde and 3-nitrotyrosine formation), and suppressed mitochondrial and histopathological injury by decreasing levels of inflammatory cytokines IL-1 beta and IL-18 (P <0.001 and P <0.01 respectively). By decreasing mitochondrial reactive oxygen species, MitoQ also suppressed activation of the NLRP3 inflammasome that was responsible for maturation of IL-1 beta and IL-18. In vitro studies demonstrated that MitoQ decreases IL-1 beta and IL-18 production in human THP-1 cells.
Taken together, our results suggest that MitoQ may have potential as a novel therapeutic agent for the treatment of acute phases of inflammatory bowel disease.
Arsenic trioxide (As2O3) is used, in current practice, as an effective chemotherapeutic agent for acute promyelocytic leukemia (APL). However, the side effects and relatively low efficacy of As2O3 in ...treating other leukemias have limited its wider use in therapeutic applications. In the present study, we found that the expression of carbonyl reductase 1 (CBR1) affects the resistance to As2O3 in leukemias, including APL; As2O3 upregulated CBR1 expression at the transcriptional level by stimulating the activity of the transcription factor activator protein-1. Moreover, CBR1 overexpression was sufficient to protect cells against As2O3 through modulation of the generation of reactive oxygen species, whereas the attenuation of CBR1 was sufficient to sensitize cells to As2O3. A combination treatment with the specific CBR1 inhibitor hydroxy-PP-Me remarkably increased As2O3-induced apoptotic cell death compared with As2O3 alone, both in vitro and in vivo. These results were confirmed in primary cultured human acute and chronic myeloid leukemia cells, with no significant cell death observed in normal leukocytes. Taken together, our findings indicate that CBR1 contributes to the low efficacy of As2O3 and, therefore, is a rational target for the development of combination chemotherapy with As2O3 in diverse leukemias including APL.
Many studies have reported that the generation of reactive oxygen species (ROS) increases during the differentiation of muscle-derived C2C12 cells. Peroxiredoxin-2 (Prx-2) is an abundant mammalian ...enzyme that protects against oxidative stress. However, the role of Prx-2 in muscle differentiation has not been investigated.
In this study, we demonstrated that Prx-2 expression increases during muscle differentiation and regeneration in response to exogenous H(2)O(2). This increase occurs only in myoblast cell lines because no increase in Prx-2 expression was observed in the NIH3T3, MEF, Chang, or HEK293 cell lines. The antioxidants, N-acetyl L-cysteine (NAC) and 4,5-dihydroxy-1,3-benzenedisulfonic acid (Tiron), both suppressed myogenesis and Prx-2 expression. Moreover, Prx-2 was upregulated at the transcriptional level by NF-κB during the differentiation of muscle-derived C2C12 cells. We also found that inhibition of phosphatidylinositol 3-kinase (PI3K) blocks NF-κB activation and suppresses Prx-2 expression. Interestingly, Prx-2 knockdown increased the expression levels of other antioxidant enzymes, including all of the other Prx family member, thioredoxin-1 (Trx-1) and catalase, but also enhanced the accumulation of endogenous ROS during muscle differentiation.
In this study, we demonstrated for the first time that Prx-2 is unregulated during the muscle differentiation and regeneration.
Prx-2 is upregulated via the PI3K/NF-κB pathway and attenuates oxidative stress during muscle differentiation and regeneration.
In this paper, mesoporous nanosheet-based ZnO hierarchical structures decorated with Ag nanoparticles were synthesized via a simple, rapid, environment-friendly and cost-effective one pot synthesis ...approach using NaOH as the precipitating agent. Field emission scanning electron microscopy (FE-SEM), transmission electron microscopy (TEM), X-ray diffraction (XRD), Fourier transform infrared (FTIR) spectroscopy and photoluminescence (PL) spectroscopy were performed in order to investigate the morphology, crystalline structure and molecular nature of the as-synthesized composite. Several rod shaped nanosheets assembled as petals were synthesized with metal particles well-dispersed on their surface. The photocatalytic performance of the nanocatalyst was tested using Rhodamine B (RhB) as the organic pollutant and results revealed that Ag/ZnO composites have higher photocatalytic efficiency as compared to pure ZnO. ZnO composites also showed enhanced antibacterial property in the zone of inhibition test using Escherichia coli (E.coli) as the bacterial strain.
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