63 research outputs found
Attenuation of doxorubicin-induced cardiotoxicity by mdivi-1: a mitochondrial division/mitophagy inhibitor
Doxorubicin is one of the most effective anti-cancer agents. However, its use is associated with adverse cardiac effects, including cardiomyopathy and progressive heart failure. Given the multiple beneficial effects of the mitochondrial division inhibitor (mdivi-1) in a variety of pathological conditions including heart failure and ischaemia and reperfusion injury, we investigated the effects of mdivi-1 on doxorubicin-induced cardiac dysfunction in naĂŻve and stressed conditions using Langendorff perfused heart models and a model of oxidative stress was used to assess the effects of drug treatments on the mitochondrial depolarisation and hypercontracture of cardiac myocytes. Western blot analysis was used to measure the levels of p-Akt and p-Erk 1/2 and flow cytometry analysis was used to measure the levels p-Drp1 and p-p53 upon drug treatment. The HL60 leukaemia cell line was used to evaluate the effects of pharmacological inhibition of mitochondrial division on the cytotoxicity of doxorubicin in a cancer cell line. Doxorubicin caused a significant impairment of cardiac function and increased the infarct size to risk ratio in both naĂŻve conditions and during ischaemia/reperfusion injury. Interestingly, co-treatment of doxorubicin with mdivi-1 attenuated these detrimental effects of doxorubicin. Doxorubicin also caused a reduction in the time taken to depolarisation and hypercontracture of cardiac myocytes, which were reversed with mdivi-1. Finally, doxorubicin caused a significant elevation in the levels of signalling proteins p-Akt, p-Erk 1/2, p-Drp1 and p-p53. Co-incubation of mdivi-1 with doxorubicin did not reduce the cytotoxicity of doxorubicin against HL-60 cells. These data suggest that the inhibition of mitochondrial fission protects the heart against doxorubicin-induced cardiac injury and identify mitochondrial fission as a new therapeutic target in ameliorating doxorubicin-induced cardiotoxicity without affecting its anti-cancer properties
Oxygen reduction reaction features in neutral media on glassy carbon electrode functionalized by chemically prepared gold nanoparticles
Gold nanoparticles (AuNPs) were prepared by chemical route using 4 different protocols by varying reducer, stabilizing agent and solvent mixture. The obtained AuNPs were characterized by transmission electronic microscopy (TEM), UV-Visible and zeta potential measurements. From these latter surface charge densities were calculated to evidence the effect of the solvent mixture on AuNPs stability. The AuNPs were then deposited onto glassy carbon (GC) electrodes by drop-casting and the resulting deposits were characterized by cyclic voltammetry (CV) in H2SO4 and field emission gun scanning electron microscopy (FEG-SEM). The electrochemical kinetic parameters of the 4 different modified electrodes towards oxygen reduction reaction (ORR) in neutral NaCl-NaHCO3 media (0.15 M / 0.028 M, pH 7.4) were evaluated by rotating disk electrode voltammetry and subsequent Koutecky-Levich treatment. Contrary to what we previously obtained with electrodeposited AuNPs [Gotti et al., Electrochim. Acta 2014], the highest cathodic transfer coefficients were not obtained on the smallest particles, highlighting the influence of the stabilizing ligand together with the deposits morphology on the ORR kinetics
Tuning the Stability of Organic Active Materials for Nonaqueous Redox Flow Batteries via Reversible, Electrochemically Mediated Li<sup>+</sup> Coordination
We describe an electrochemically
mediated interaction between Li<sup>+</sup> and a promising active
material for nonaqueous redox flow
batteries (RFBs), 1,2,3,4-tetrahydro-6,7-dimethoxy-1,1,4,4-tetramethylnaphthalene
(TDT), and the impact of this structural interaction on material stability
during voltammetric cycling. TDT could be an advantageous organic
positive electrolyte material for nonaqueous RFBs due to its high
oxidation potential, 4.21 V vs Li/Li<sup>+</sup>, and solubility of
at least 1.0 M in select electrolytes. Although results from voltammetry
suggest TDT displays Nernstian reversibility in many nonaqueous electrolyte
solutions, bulk electrolysis reveals significant degradation in all
electrolytes studied, the extent of which depends on the electrolyte
solution composition. Results of subtractively normalized in situ
Fourier transform infrared spectroscopy (SNIFTIRS) confirm that TDT
undergoes reversible structural changes during cyclic voltammetry
in propylene carbonate and 1,2-dimethoxyethane solutions containing
Li<sup>+</sup> electrolytes, but irreversible degradation occurs when
tetrabutylammonium (TBA<sup>+</sup>) replaces Li<sup>+</sup> as the
electrolyte cation in these solutions. By combining the results from
SNIFTIRS experiments with calculations from density functional theory,
solution-phase active species structure and potential-dependent interactions
can be determined. We find that Li<sup>+</sup> coordinates to the
Lewis basic methoxy groups of neutral TDT and, upon electrochemical
oxidation, this complex dissociates into the radical cation TDT<sup>•+</sup> and Li<sup>+</sup>. The improved cycling stability
in the presence of Li<sup>+</sup> relative to TBA<sup>+</sup> suggests
that the structural interaction reported herein may be advantageous
to the design of energy storage materials based on organic molecules
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