scholarly journals Efficacy of a Low Dose of Estrogen on Antioxidant Defenses and Heart Rate Variability

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Cristina Campos ◽  
Karina Rabello Casali ◽  
Dhãniel Baraldi ◽  
Adriana Conzatti ◽  
Alex Sander da Rosa Araújo ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Hydrogen Peroxide ◽  
Heart Rate ◽  
Heart Rate Variability ◽  
Superoxide Anion ◽  
Low Dose ◽  
Estrogen Therapy ◽  
Antioxidant Defenses ◽  
High Dose ◽  
Hemodynamic Assessment

This study tested whether a low dose (40% less than the pharmacological dose of 17-βestradiol) would be as effective as the pharmacological dose to improve cardiovascular parameters and decrease cardiac oxidative stress. Female Wistar rats (n=9/group) were divided in three groups: (1) ovariectomized (Ovx), (2) ovariectomized animals treated for 21 days with low dose (LE; 0.2 mg), and (3) high dose (HE; 0.5 mg) 17-βestradiol subcutaneously. Hemodynamic assessment and spectral analysis for evaluation of autonomic nervous system regulation were performed. Myocardial superoxide dismutase (SOD) and catalase (CAT) activities, redox ratio (GSH/GSSG), total radical-trapping antioxidant potential (TRAP), hydrogen peroxide, and superoxide anion concentrations were measured. HE and LE groups exhibited an improvement in hemodynamic function and heart rate variability. These changes were associated with an increase in the TRAP, GSH/GSSG, SOD, and CAT. A decrease in hydrogen peroxide and superoxide anion was also observed in the treated estrogen groups as compared to the Ovx group. Our results indicate that a low dose of estrogen is just as effective as a high dose into promoting cardiovascular function and reducing oxidative stress, thereby supporting the approach of using low dose of estrogen in clinical settings to minimize the risks associated with estrogen therapy.

Heart Rate Variability Dynamics During Low-Dose Propofol and Dexmedetomidine Anesthesia

2012 ◽  
Vol 40 (8) ◽  
pp. 1802-1813 ◽  
Author(s):  
Mika P. Tarvainen ◽  
Stefanos Georgiadis ◽  
Timo Laitio ◽  
Jukka A. Lipponen ◽  
Pasi A. Karjalainen ◽  
...  
Keyword(s):  
Heart Rate ◽  
Heart Rate Variability ◽  
Low Dose

scholarly journals Low-dose grape pomace and omija fruit extract is more effective than high-dose in lowering oxidative stress and fat-pad mass in db/db mice

2017 ◽  
Vol 26 (6) ◽  
pp. 1709-1714
Author(s):  
Su-Jung Cho ◽  
Hye-Jin Kim ◽  
Ji-Young Choi ◽  
Eun-Young Kwon ◽  
Ye Jin Kim ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Low Dose ◽  
Grape Pomace ◽  
High Dose ◽  
Fat Pad ◽  
Fruit Extract

scholarly journals Identification of Two Kinase Inhibitors with Synergistic Toxicity with Low-Dose Hydrogen Peroxide in Colorectal Cancer Cells In vitro

Cancers ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 122 ◽  
Author(s):  
Eric Freund ◽  
Kim-Rouven Liedtke ◽  
Lea Miebach ◽  
Kristian Wende ◽  
Amanda Heidecke ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Colorectal Cancer ◽  
Hydrogen Peroxide ◽  
Protein Kinase ◽  
Tumor Cells ◽  
Low Dose ◽  
Kinase Inhibitors ◽  
Protein Kinase Inhibitors ◽  
Colorectal Cancer Cells

Colorectal carcinoma is among the most common types of cancers. With this disease, diffuse scattering in the abdominal area (peritoneal carcinosis) often occurs before diagnosis, making surgical removal of the entire malignant tissue impossible due to a large number of tumor nodules. Previous treatment options include radiation and its combination with intraperitoneal heat-induced chemotherapy (HIPEC). Both options have strong side effects and are often poor in therapeutic efficacy. Tumor cells often grow and proliferate dysregulated, with enzymes of the protein kinase family often playing a crucial role. The present study investigated whether a combination of protein kinase inhibitors and low-dose induction of oxidative stress (using hydrogen peroxide, H2O2) has an additive cytotoxic effect on murine, colorectal tumor cells (CT26). Protein kinase inhibitors from a library of 80 substances were used to investigate colorectal cancer cells for their activity, morphology, and immunogenicity (immunogenic cancer cell death, ICD) upon mono or combination. Toxic compounds identified in 2D cultures were confirmed in 3D cultures, and additive cytotoxicity was identified for the substances lavendustin A, GF109203X, and rapamycin. Toxicity was concomitant with cell cycle arrest, but except HMGB1, no increased expression of immunogenic markers was identified with the combination treatment. The results were validated for GF109203X and rapamycin but not lavendustin A in the 3D model of different colorectal (HT29, SW480) and pancreatic cancer cell lines (MiaPaca, Panc01). In conclusion, our in vitro data suggest that combining oxidative stress with chemotherapy would be conceivable to enhance antitumor efficacy in HIPEC.

Sedative and physiologic effects of tiletamine–zolazepam following buccal administration in cats

2019 ◽  
Vol 22 (2) ◽  
pp. 108-113 ◽  
Author(s):  
Pablo Nejamkin ◽  
Verónica Cavilla ◽  
María Clausse ◽  
Florencia Landivar ◽  
Augusto M Lorenzutti ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Low Dose ◽  
Sedation Score ◽  
High Dose ◽  
Physiological Effects ◽  
Chemical Restraint ◽  
Hemoglobin Saturation ◽  
Baseline Systolic Blood Pressure ◽  
Over Time

Objectives The aim of this study was to describe the sedative and some physiological effects of tiletamine–zolazepam following buccal administration (BA) in cats. Methods Seven healthy spayed European shorthair cats (three males, four females) were studied twice in this randomized, blinded, crossover study. Each cat received two doses of tiletamine–zolazepam by BA: the low-dose (LD) group consisted of 5 mg/kg of each drug, and the high-dose (HD) group consisted of 7.5 mg/kg of each. Baseline systolic blood pressure (SAP), heart rate (HR), respiratory rate (RR) and a sedation score were recorded prior to administration of each treatment. The same variables plus the percentage of hemoglobin saturated with oxygen as measured by pulse oximetry (SpO2) were recorded at predefined intervals for the next 2 h. Results All cats completed the study. No retching or vomiting were observed. Hypersalivation was observed in 0/7 and 3/7 for LD and HD groups, respectively ( P = 0.2). There were significant changes in scores over time for posture, response to clippers and response to manual restraint for both groups, without differences between groups. RR, HR and SAP changed significantly over time. SAP and RR were significantly lower for the HD than for the LD group. No values for hemoglobin saturation <95% were observed. Conclusions and relevance BA of tiletamine–zolazepam at the doses studied here is a simple and effective method for chemical restraint in cats, where the LD group had a lower impact on SAP and RR than the HD group.

scholarly journals Endotoxin depresses heart rate variability in mice: cytokine and steroid effects

2009 ◽  
Vol 297 (4) ◽  
pp. R1019-R1027 ◽  
Author(s):  
Karen D. Fairchild ◽  
Jeffrey J. Saucerman ◽  
Laura L. Raynor ◽  
Joseph A. Sivak ◽  
Yuping Xiao ◽  
...  
Keyword(s):  
Heart Rate ◽  
Heart Rate Variability ◽  
High Frequency ◽  
High Dose ◽  
Biphasic Response ◽  
Dexamethasone Treatment ◽  
Life Threatening ◽  
Surgical Implantation ◽  
Temporally Correlated

Heart rate variability (HRV) falls in humans with sepsis, but the mechanism is not well understood. We utilized a mouse model of endotoxemia to test the hypothesis that cytokines play a role in abnormal HRV during sepsis. Adult male C57BL/6 mice underwent surgical implantation of probes to continuously monitor electrocardiogram and temperature or blood pressure via radiotelemetry. Administration of high-dose LPS ( Escherichia coli LPS, 10 mg/kg, n = 10) caused a biphasic response characterized by an early decrease in temperature and heart rate at 1 h in some mice, followed by a prolonged period of depressed HRV in all mice. Further studies showed that LPS doses as low as 0.01 mg/kg evoked a significant decrease in HRV. With high-dose LPS, the initial drops in temperature and HR were temporally correlated with peak expression of TNFα 1 h post-LPS, whereas maximal depression in HRV coincided with peak levels of multiple other cytokines 3–9 h post-LPS. Neither hypotension nor hypothermia explained the HRV response. Pretreatment with dexamethasone prior to LPS significantly blunted expression of 7 of the 10 cytokines studied and shortened the duration of depressed HRV by about half. Interestingly, dexamethasone treatment alone caused a dramatic increase in both low- and high-frequency HRV. Administration of recombinant TNFα caused a biphasic response in HR and HRV similar to that caused by LPS. Understanding the role of cytokines in abnormal HRV during sepsis could lead to improved strategies for detecting life-threatening nosocomial infections in intensive care unit patients.

GSH transport in mitochondria: defense against TNF-induced oxidative stress and alcohol-induced defect

1997 ◽  
Vol 273 (1) ◽  
pp. G7-G17 ◽  
Author(s):  
J. C. Fernandez-Checa ◽  
N. Kaplowitz ◽  
C. Garcia-Ruiz ◽  
A. Colell ◽  
M. Miranda ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Hydrogen Peroxide ◽  
Plasma Membrane ◽  
Molecular Oxygen ◽  
Respiratory Chain ◽  
Superoxide Anion ◽  
Complex Iii ◽  
Contributory Factor ◽  
Xenopus Laevis Oocytes ◽  
Mitochondrial Matrix

Mitochondria generate reactive oxygen species (ROS) as byproducts of molecular oxygen consumption in the electron transport chain. Most cellular oxygen is consumed in the cytochrome-c oxidase complex of the respiratory chain, which does not generate reactive species. The ubiquinone pool of complex III of respiration is the major site within the respiratory chain that generates superoxide anion as a result of a single electron transfer to molecular oxygen. Superoxide anion and hydrogen peroxide, derived from the former by superoxide dismutase, are precursor of hydroxyl radical through the participation of transition metals. Glutathione (GSH) in mitochondria is the only defense available to metabolize hydrogen peroxide. A small fraction of the total cellular GSH pool is sequestered in mitochondria by the action of a carrier that transports GSH from the cytosol to the mitochondrial matrix. Mitochondria are not only one of the main cellular sources of ROS, they also are a key target of ROS. Mitochondria are subcellular targets of cytokines, especially tumor necrosis factor (TNF); depletion of GSH in this organelle renders the cell more susceptible to oxidative stress originating in mitochondria. Ceramide generated during TNF signaling leads to increased production of ROS in mitochondria. Chronic ethanol-fed hepatocytes are selectively depleted of GSH in mitochondria due to a defective operation of the carrier responsible for transport of GSH from the cytosol into the mitochondrial matrix. Under these conditions, limitation of the mitochondrial GSH pool represents a critical contributory factor that sensitizes alcoholic hepatocytes to the prooxidant effects of cytokines and prooxidants generated by oxidative metabolism of ethanol. S-adenosyl-L-methionine prevents development of the ethanol-induced defect. The mitochondrial GSH carrier has been functionally expressed in Xenopus laevis oocytes microinjected with mRNA from rat liver. This critical carrier displays functional characteristics distinct from other plasma membrane GSH carriers, such as its ATP dependency, inhibitor specificity, and the size class of mRNA that encode the corresponding carrier, suggesting that the mitochondrial carrier of GSH is a gene product distinct from the plasma membrane transporters.

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