scholarly journals Low Energy Visible Light Induces Reactive Oxygen Species Generation and Stimulates an Increase of Intracellular Calcium Concentration in Cardiac Cells

2003 ◽  
Vol 278 (42) ◽  
pp. 40917-40922 ◽  
Author(s):  
Ronit Lavi ◽  
Asher Shainberg ◽  
Harry Friedmann ◽  
Vladimir Shneyvays ◽  
Ophra Rickover ◽  
...  
1997 ◽  
Vol 272 (6) ◽  
pp. G1439-G1450 ◽  
Author(s):  
K. Bielefeldt ◽  
C. A. Whiteis ◽  
R. V. Sharma ◽  
F. M. Abboud ◽  
J. L. Conklin

Reactive oxygen species (ROS) significantly alter cell function. We examined the effects of hydrogen peroxide (H2O2) and xanthine/xanthine oxidase (X/XO) on isolated intestinal muscle cells. We assessed cell viability with the exclusion dye trypan blue and assayed the effects of H2O2 and X/XO on the intracellular redox state with the fluorescent probe 2',7'-dichlorofluorescein. Intracellular calcium concentration was measured in cells loaded with fura 2-acetoxymethyl ester, and we recorded whole membrane currents with conventional patch-clamp methods. Cells remained viable after a 5-min exposure to H2O2 and X/XO. H2O2 and X/XO led to a significant rise of the intracellular concentration of ROS. H2O2 (270 microM to 2.7 mM) as well as X/XO (0.25-16 mU; 0.5 mM xanthine) significantly increased intracellular calcium concentrations. Depletion of intracellular calcium with ryanodine or thapsigargin did not abolish the effect of ROS on the intracellular calcium concentration. In the absence of external calcium or in the presence of the calcium channel blocker nifedipine, H2O2 and X/XO still increased the intracellular calcium level. Thus calcium influx and calcium release from internal stores contributed to this rise in cytosolic calcium. Catalase and superoxide dismutase blunted or completely abolished the changes in calcium concentration elicited by H2O2 and X/XO. Exposure to ROS resulted in a rapid decline of the membrane resistance without significant changes in voltage-sensitive ion currents. We conclude that ROS disrupt the calcium homeostasis of cells at concentrations that do not lead to immediate cell death. The resulting elevation in cytosolic free calcium will activate a variety of biochemical reactions and may thus contribute to the cytotoxicity of reactive oxygen molecules.


2017 ◽  
Vol 1 (S1) ◽  
pp. 7-7
Author(s):  
Trevi A. Mancilla ◽  
Gregory J. Aune

OBJECTIVES/SPECIFIC AIMS: Our research strives to understand the pathophysiology of doxorubicin cardiotoxicity, focusing on the understudied nonmyocyte cardiac cells. Our understanding will enable researchers to develop protective or alternative therapies for cancer patients and treatments for cancer survivors. METHODS/STUDY POPULATION: Early studies have been carried out in isolated primary cardiac fibroblasts. Cells were treated with varying doses of doxorubicin. Cell viability, proliferation, and reactive oxygen species generation have all been studied. Future studies will focus on mitochondrial assessment in treated cells and confirmation of findings in animal models. Potential therapies discovered in these studies will also be conducted in animal models. RESULTS/ANTICIPATED RESULTS: Our results show a direct effect of doxorubicin on cardiac fibroblasts in vitro. Treated cells show a decreased rate of proliferation and increased production of reactive oxygen species. Similarly to cardiomyocytes, we hypothesize that reactive oxygen species damage the mitochondria of cardiac fibroblasts thereby altering their function and playing a role in doxorubicin cardiotoxicity. DISCUSSION/SIGNIFICANCE OF IMPACT: Current therapies have not been able to adequately protect patients from the cardiotoxicity of doxorubicin and other anthracyclines. A complete understanding of how doxorubicin damages cardiac tissue will only be possible by studying all cell types of the heart. With a better understanding, alternative therapies can be developed to prevent or treat doxorubicin cardiotoxicity without sacrificing the efficacy of doxorubicin in treating cancer.


The eff ect of the non-opiate analog of leu-enkephalin (peptide NALE: Phe – D – Ala – Gly – Phe – Leu – Arg) on the reactive oxygen species generation in the heart of albino rats in the early postnatal period was studied. Peptide NALE was administered intraperitoneally in the dose of 100 μ/kg daily from 2 to 6 days of life. Reactive oxygen species generation was assessed by chemiluminescence in the heart homogenates of 7-day-old animals. Decreasing of reactive oxygen species generation nearly by 30 % and an increasing in antioxidant system activity by the 20-27 %, compared with the control parameters, were found. The antioxidant eff ect of peptide NALE is associated with the presence of the amino acid Arg in the structure of the peptide. An analogue of NALE peptide, devoid of Arg (peptide Phe – D – Ala – Gly – Phe – Leu – Gly), had a signifi cant lower antioxidant eff ect. The NO-synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME) in the dose 50 mg/kg, administered with NALE peptide, reduced the severity of the NALE antioxidant eff ect. The results of the study suggest that the pronounced antioxidant eff ect of NALE peptide in the heart of albino rats, at least in part, is due to the interaction with the nitric oxide system.


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