scholarly journals Endogenous Estrogen-Mediated Heme Oxygenase Regulation in Experimental Menopause

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Anikó Pósa ◽  
Renáta Szabó ◽  
Anett Csonka ◽  
Médea Veszelka ◽  
Anikó Magyariné Berkó ◽  
...  
Keyword(s):  
Left Ventricle ◽  
Heme Oxygenase ◽  
Protoporphyrin Ix ◽  
Control Group ◽  
St Segment ◽  
Female Wistar Rats ◽  
Endogenous Estrogen ◽  
Estrogen Depletion ◽  
Cardiac Left Ventricle

Estrogen deficiency is one of the main causes of age-associated diseases in the cardiovascular system. Female Wistar rats were divided into four experimental groups: pharmacologically ovariectomized, surgically ovariectomized, and 24-month-old intact aging animals were compared with a control group. The activity and expression of heme oxygenases (HO) in the cardiac left ventricle, the concentrations of cardiac interleukin-6 (IL-6) and tumor necrosis factor-α(TNF-α), the myeloperoxidase (MPO) activity in the cardiac left ventricle, and the effects of heme oxygenase blockade (by 24-hour and 1-hour pretreatment with tin-protoporphyrin IX, SnPP) on the epinephrine and phentolamine-induced electrocardiogram ST segment changesin vivowere investigated. The cardiac HO activity and the expression of HO-1 and HO-2 were significantly decreased in the aged rats and after ovariectomy. Estrogen depletion was accompanied by significant increases in the expression of IL-6 and TNF-α. The aged and ovariectomized animals exhibited a significantly elevated MPO activity and a significant ST segment depression. After pretreatment with SnPP augmented ST segment changes were determined. These findings demonstrate that the sensitivity to cardiac ischemia in estrogen depletion models is associated with suppression of the activity and expression of the HO system and increases in the secretion of proinflammatory cytokines and biomarkers.

The protective properties of synthetic porphyrin tin complexes in toxic hyperbilirubinemia

2000 ◽  
Vol 04 (03) ◽  
pp. 243-247 ◽  
Author(s):  
T. O. PHILIPPOVA ◽  
B. N. GALKIN ◽  
N. YA. GOLOVENKO ◽  
Z. I. ZHILINA ◽  
S. V. VODZINSKII
Keyword(s):  
Heme Oxygenase ◽  
Serum Bilirubin ◽  
Protoporphyrin Ix ◽  
Serum Bilirubin Level ◽  
Oxygenase Activity ◽  
Tetraphenyl Porphyrin ◽  
Tin Complexes ◽  
Cytochrome P 450

Tin complexes of meso-substituted synthetic porphyrins, namely Sn 4+-meso-tetraphenyl- porphyrin ( Sn - TPP ) and Sn 4+-meso-tetrakis(N-methyl-3-pyridyl)porphyrin tetratosylate ( Sn - TMe -3- PyP ), efficiently decrease the serum bilirubin level when injected subcutaneously at a dose of 100 μM kg−1 body weight into mice. These compounds are active during hyperbilirubinemia, induced by phenylhydrazine, hemin and tetrachloromethane, and also during autoimmune hemolytic anemia. In the latter case a decrease in serum bilirubin content was observed, as well as a decrease in the amount of blood reticulocytes which reflects a milder course of the disease. The Sn complexes under study induce, in vivo, cytochrome P-450, inhibit microsomal heme oxygenase and decrease the intensity of lipid peroxidation. At the same time, in vitro the hepatic and splenic heme oxygenase activity is blocked only when a 0.1 μM concentration of Sn - TMe -3- PyP or Sn -protoporphyrin IX is added to the incubation mixture. Sn - TPP does not affect the activity of this enzyme in vitro.

Heme oxygenase attenuates allergen-induced airway inflammation and hyperreactivity in guinea pigs

2004 ◽  
Vol 287 (1) ◽  
pp. L26-L34 ◽  
Author(s):  
Abdelhamid Almolki ◽  
Camille Taillé ◽  
Gillian F. Martin ◽  
Peter J. Jose ◽  
Christine Zedda ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Airway Inflammation ◽  
Heme Oxygenase ◽  
Guinea Pigs ◽  
Protoporphyrin Ix ◽  
Airway Responsiveness ◽  
Mucus Secretion ◽  
Control Group ◽  
Repeated Administrations ◽  
Tin Protoporphyrin

Heme oxygenase (HO), the heme-degrading enzyme, has shown anti-inflammatory effects in several models of pulmonary diseases. HO is induced in airways during asthma; however, its functional role is unclear. Therefore, we evaluated the role of HO on airway inflammation [evaluated by bronchoalveolar lavage (BAL) cellularity and BAL levels of eotaxin, PGE2, and proteins], mucus secretion (evaluated by analysis of MUC5AC gene expression and periodic acid-Schiff staining), oxidative stress (evaluated by quantification of 4-hydroxynonenal adducts and carbonylated protein levels in lung homogenates), and airway responsiveness to histamine in ovalbumin (OVA)-sensitized and multiple aerosol OVA or saline-challenged guinea pigs (6 challenges, once daily, OVA group and control group, respectively). Airway inflammation, mucus secretion, oxidative stress, and responsiveness were significantly increased in the OVA group compared with the control group. HO upregulation by repeated administrations of hemin (50 mg/kg ip) significantly decreased airway responsiveness in control animals and airway inflammation, mucus secretion, oxidative stress, and responsiveness in OVA animals. These effects were reversed by the concomitant administration of the HO inhibitor tin protoporphyrin-IX (50 μmol/kg ip). Repeated administrations of tin protoporphyrin-IX alone significantly increased airway responsiveness in control animals but did not modify airway inflammation, mucus secretion, oxidative stress, and responsiveness in OVA animals. These results suggest that upregulation of the HO pathway has a significant protective effect against airway inflammation, mucus hypersecretion, oxidative stress, and hyperresponsiveness in a model of allergic asthma in guinea pigs.

scholarly journals Architecture and Composition Dictate Viscoelastic Properties of Organ-Derived Extracellular Matrix Hydrogels

Polymers ◽  
2021 ◽  
Vol 13 (18) ◽  
pp. 3113
Author(s):  
Francisco Drusso Martinez-Garcia ◽  
Roderick Harold Jan de Hilster ◽  
Prashant Kumar Sharma ◽  
Theo Borghuis ◽  
Machteld Nelly Hylkema ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Stress Relaxation ◽  
Left Ventricle ◽  
Viscoelastic Properties ◽  
Maxwell Model ◽  
Architectural Support ◽  
Dependent Part ◽  
Physical Features ◽  
Cardiac Left Ventricle

The proteins and polysaccharides of the extracellular matrix (ECM) provide architectural support as well as biochemical and biophysical instruction to cells. Decellularized, ECM hydrogels replicate in vivo functions. The ECM’s elasticity and water retention renders it viscoelastic. In this study, we compared the viscoelastic properties of ECM hydrogels derived from the skin, lung and (cardiac) left ventricle and mathematically modelled these data with a generalized Maxwell model. ECM hydrogels from the skin, lung and cardiac left ventricle (LV) were subjected to a stress relaxation test under uniaxial low-load compression at a 20%/s strain rate and the viscoelasticity determined. Stress relaxation data were modelled according to Maxwell. Physical data were compared with protein and sulfated GAGs composition and ultrastructure SEM. We show that the skin-ECM relaxed faster and had a lower elastic modulus than the lung-ECM and the LV-ECM. The skin-ECM had two Maxwell elements, the lung-ECM and the LV-ECM had three. The skin-ECM had a higher number of sulfated GAGs, and a highly porous surface, while both the LV-ECM and the lung-ECM had homogenous surfaces with localized porous regions. Our results show that the elasticity of ECM hydrogels, but also their viscoelastic relaxation and gelling behavior, was organ dependent. Part of these physical features correlated with their biochemical composition and ultrastructure.

Endothelial cell heme oxygenase and ferritin induction in rat lung by hemoglobin in vivo

1995 ◽  
Vol 268 (2) ◽  
pp. L321-L327 ◽  
Author(s):  
J. Balla ◽  
K. A. Nath ◽  
G. Balla ◽  
M. B. Juckett ◽  
H. S. Jacob ◽  
...  
Keyword(s):  
Heme Oxygenase ◽  
Protoporphyrin Ix ◽  
Heme Iron ◽  
Pulmonary Vasculature ◽  
Microvascular Endothelium ◽  
Mrna Accumulation ◽  
Mrna Induction ◽  
Rat Lungs

Iron-derived reactive oxygen species play an important role in the pathogenesis of various vascular disorders including vasculitis, atherosclerosis, and capillary leak syndromes such as the adult respiratory distress syndrome (ARDS). We have suggested that acute incorporation of the heme moiety of hemoglobin released from red blood cells into endothelium could provide catalytically active iron to the vasculature. Adaptation to chronic heme stress involves the induction of heme oxygenase and ferritin; the latter provides cytoprotection against free radicals in vitro. The present studies examine the bioavailability of heme, derived from hemoglobin, to induce heme oxygenase and ferritin in rat lungs in vivo. Intravenous injection of methemoglobin, but not oxyhemoglobin, increases total lung heme oxygenase mRNA approximately fivefold after 16 h. Accompanying this mRNA induction, expression of total lung heme oxygenase enzyme activity is also markedly enhanced. In situ hybridization for heme oxygenase reveals mRNA accumulation in the lung microvascular endothelium, implying incorporation of heme into endothelial cells. Similarly, methemoglobin significantly increases the ferritin protein content of rat lungs and in parallel, ferritin light-chain mRNA increases approximately 1.6-fold, whereas heavy-chain mRNA is upregulated by approximately 1.9-fold. Immunoreactive ferritin is present in lung microvascular endothelium after methemoglobin treatment, suggesting incorporation of heme iron into pulmonary vasculature. Subcutaneous injection of Sn-protoporphyrin IX, a competitive inhibitor of heme oxygenase, does not affect methemoglobin-induced ferritin synthesis in lungs. We speculate that methemoglobin, which might be generated by activated leukocytes in ARDS associated with disseminated interavascular coagulation, can provide heme iron to lung microvascular endothelium to induce heme oxygenase and ferritin.

scholarly journals Assessment of caspase-3 activity in rabbit myocardial tissue during experimental hemodynamic overload of the left ventricle of the heart

2010 ◽  
Vol 56 (6) ◽  
pp. 719-725
Author(s):  
M.L. Blagonravov ◽  
M.V. Onufriev ◽  
E.A. Demurov ◽  
N.V. Guliaeva ◽  
V.A. Frolov
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Left Ventricle ◽  
Caspase 3 ◽  
Ascending Aorta ◽  
Control Group ◽  
Myocardial Tissue ◽  
Hemodynamic Overload ◽  
Cardiac Ventricles ◽  
Cardiac Left Ventricle

It's well known that chronic overload of the cardiac left ventricle is accompanied by an increase in the cardiomyocyte apoptosis rate. However direction and extent of programmed cell death changes under an acute overload of the left ventricle still requires detailed investigation. Caspase-3 activity has been investigated in myocardium of rabbits on the 1, 3 and 5 days after modeling of left ventricle hemodynamic overload caused by surgical narrrowing of the ascending aorta. Control group included intact animals. It was found that caspase-3 activity significantly increased in both ventricles on day 1; it increased more than twofold above controls on day 3; it began to decrease by day 5. On the basis of the obtained data it was concluded that: an acute hemodynamic overload of the left ventricle is a cause of apoptosis acceleration in the myocardial tissue of both cardiac ventricles during first days of the investigated process.

scholarly journals Therapeutic Effect of 48 h after Nigella sativa Extract Administration on Female Wistar Rats Vaginal Candidiasis Model: An Experimental Study

2021 ◽  
Vol 9 (T3) ◽  
pp. 6-8
Author(s):  
Muhammad Rusda ◽  
Ichwanul Adenin ◽  
M. Fidel Ganis Siregar ◽  
Andrina Y. M. Rambe ◽  
Yudha Sudewo
Keyword(s):  
Therapeutic Effect ◽  
Group Treatment ◽  
Nigella Sativa ◽  
Vaginal Candidiasis ◽  
Control Group ◽  
Therapeutic Effects ◽  
Post Inoculation ◽  
Common Causes ◽  
Female Wistar Rats

BACKGROUND: Candida albicans was the common causes of vulvovaginalis candidiasis (VVC) in human. To avoid complications, prompt and proper treatment of VVC must be performed. The pharmacological effects of Nigella sativa include antimicrobial, anti-inflammatory, immune stimulation, and anti-cancer properties. AIM: N. sativa has been shown to have an in vivo antifungal effect and the purpose of this study was to determine the antifungal and potential in vivo therapeutic effects. METHODS: This research was an empirical study which evaluated the therapeutic effect of the vaginal candidiasis model of N. sativa in rats. The subjects were 28 rats inoculated with C. albicans and were divided into four groups: Control group (G1), fluconazole group (G2), N. sativa group (G3), and N. sativa and fluconazole group combinations (G4). The colony of C. albicans was assessed to determine the treatment’s therapeutic effect. RESULTS: There was no difference in the number of colonies of C. albicans between all the pre-inoculation (p = 0.274) and post-inoculation (p = 0.323) classes. A substantial decrease in the number of C. albicans colonies within 48 h of treatment was observed between the three control group treatment forms (N. sativa group p = 0.046; fluconazole group p = 0.002; and N. sativa + fluconazole group p = 0.002). CONCLUSIONS: The therapeutic effect of N. sativa has been achieved by reducing the number of colonies of C. albicans.

scholarly journals Cardioprotective Effect of Selective Estrogen Receptor Modulator Raloxifene Are Mediated by Heme Oxygenase in Estrogen-Deficient Rat

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Anikó Posa ◽  
Renáta Szabó ◽  
Krisztina Kupai ◽  
Anikó Magyariné Berkó ◽  
Médea Veszelka ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Heme Oxygenase ◽  
Blood Pressure Response ◽  
Pharmacological Inhibition ◽  
Beneficial Effects ◽  
Receptor Modulator ◽  
St Segment ◽  
Inflammatory State ◽  
Negative Impacts

Estrogens and raloxifene (RAL) have beneficial effects on certain cardiovascular indices in postmenopausal women characterized by estrogen deficiency. Heme oxygenase (HO) activity is increased by 17β-estradiol (E2) and RAL in estrogen-deficient rat resulting in vasorelaxation mediated by carbon monoxide. We determined the expressions of HO in cardiac and aortic tissues after ovariectomy (OVX) and subsequent RAL or E2treatment. We investigated the effects of pharmacological inhibition of HO enzyme on the arginine vasopressin- (AVP-) induced blood pressure in vivo, the epinephrine- and phentolamine-induced electrocardiogram ST segment changes in vivo, and the myeloperoxidase (MPO) enzyme activity. When compared with intact females, OVX decreased the HO-1 and HO-2 expression, aggravated the electrocardiogram signs of heart ischemia and the blood pressure response to AVP, and increased the cardiac MPO. E2and RAL are largely protected against these negative impacts induced by OVX. The pharmacological inhibition of HO in E2- or RAL-treated OVX animals, however, restored the cardiovascular status close to that observed in nontreated OVX animals. The decreased expression of HO enzymes and the changes in blood pressure ischemia susceptibility and inflammatory state in OVX rat can be reverted by the administration of E2or RAL partly through its antioxidant and anti-inflammatory roles.

scholarly journals In vivo study of the antihypertensive effect of bidara leaf (Ziziphus spina-christi) during pregnancy

MEDISAINS ◽  
2021 ◽  
Vol 19 (2) ◽  
pp. 35
Author(s):  
Tasya Nurlaila Dilla ◽  
Suharyo Hadisaputro ◽  
Aris Santjaka
Keyword(s):  
Blood Pressure ◽  
Leaf Extract ◽  
Dose Group ◽  
Control Group ◽  
Pregnant Rats ◽  
Free Radical Damage ◽  
Drought Tolerant ◽  
Female Wistar Rats ◽  
Tropical Climates

Background: Bidara is drought tolerant and very easy to grow in tropical climates such as Indonesia. Bidara contains a combination of calcium, potassium, and magnesium, and active flavonoid compounds, and antioxidant activity that play a role in inhibiting free radical damage, improving endothelial function so that it can potentially lower blood pressure. Previous studies explained that a dose variant of no more than 300mg/kg BW is beneficial while minimizing pathological changes. However, there has been no research related to the effect of bidara leaf in lowering blood pressure, so it is necessary to do related research.Objective: Analyze the effect of bidara leaf extract at a 200 mg/kg BW dose and 300 mg/kg BW on systolic and diastolic blood pressure.Methods: 24 pregnant female Wistar rats induced hypertension, aged 6-8 weeks with a weight of 130-230 grams. The rats were randomized so that they consisted of 2 control groups and two experimental groups, which were given various doses of bidara leaf for nine days. Blood pressure was measured using non-invasive CODA.Results: The blood pressure of rats in the bidara leaf extract group at doses of 200mg/kg BW and 300mg/kg BW decreased systolic and diastolic compared to the control group (p<0.05). The 200mg/kg BW dose group experienced a decrease in blood pressure of 12.3% for systolic and 16.32% for diastolic; the 300mg/kg BW dose group experienced a decrease in blood pressure of 19.99% for systolic and 27.73% for diastolic.Conclusion: Bidara leaf extract can reduce the blood pressure of pregnant rats with hypertension.

Abstract 260: Cardiosphere Derived Cells Generated from the Human Atria Exhibit Superior Potency Compared to the Left Ventricle

2013 ◽  
Vol 113 (suppl_1) ◽  
Author(s):  
David L Simpson ◽  
Agnieszka Blusztajn ◽  
Ileana Valle ◽  
Michelle Kreke ◽  
Linda Marban ◽  
...  
Keyword(s):  
Left Ventricle ◽  
Control Group ◽  
Cell Bank ◽  
Tissue Samples ◽  
Dna Microarray Data ◽  
Master Cell Bank ◽  
Normal Human ◽  
Minimal Treatment ◽  
Mdr 1

Currently, allogeneic cardiosphere-derived cells (CDCs) are being tested in a phase I/II clinical trial. Our manufacturing process utilizes the atria and other regions of the heart to build a master cell bank, but leaves the left ventricle (LV) intact thus eliminating a potential source to build our clinical stocks. In an effort to increase CDC yield per heart, we compared CDCs generated from the atria to the left ventricle (LV). To investigate this hypothesis we characterized CDCs by flow cytometry, growth kinetics and in vivo potency. The surface marker profiles for atrial CDCs and LV CDCs were very similar. Of the 17 markers used to characterize CDCs (c-kit, MDR-1, Sca-1, Abcg2, CD133, CD31, CD34, CD45, CD105, CD29, CD44, CD73, CD166, CD140b, CD90, DDR2 and α-SMA) only one demonstrated substantial differential expression in LV versus atria. PDGFR-β (CD140b) was upregulated in CDCs derived from the LV compared to the atria. Consistent with this finding, GEO2R analysis of DNA microarray data revealed increased PDGFR-β and PDGF-B expression in normal human LV tissue compared to atrial tissue. We have also observed that CDC expression of PDGFR-β negatively correlates with in vivo potency (R=0.899) suggesting that the high expression of this marker in CDCs derived from the LV may limit its regenerative performance. Indeed when calculated growth rates were compared, tissue samples from the atria yielded 4 to 6-fold more CDCs compared to the LV (atria=26±10 versus LV=5±5 Million CDCs/g/day). Also, CDCs derived from the atria and LV led to differential improvements in ejection fraction (EF) over three weeks. CDCs from the atria significantly outperformed the control group (atrial CDCs=Δ+12.6±10.8%, control=Δ-15.3±13.6%), while CDCs from the LV showed minimal treatment effects and failed to meet our minimal potency requirement (LV CDCs=Δ+0.0±6.2%). In conclusion, LV CDCs display limited potential for clinical use. This observation provides a unique opportunity to explore the mechanisms that govern functional potency and assist in understanding the basic processes involved in CDC mediated repair.

scholarly journals Bile pigment formation by skin heme oxygenase: studies on the response of the enzyme to heme compounds and tissue injury.

1977 ◽  
Vol 145 (4) ◽  
pp. 1054-1059 ◽  
Author(s):  
M D Maines ◽  
J Cohn
Keyword(s):  
Enzyme Activity ◽  
Heme Oxygenase ◽  
Tissue Injury ◽  
Protoporphyrin Ix ◽  
Bile Pigment ◽  
Type B ◽  
Pigment Formation ◽  
Cobalt Protoporphyrin ◽  
Increased Activity

Skin heme oxygenase is locally elevated by stimuli such as tissue injury and injections of whole blood, myoglobin, and hematin. The enzyme activity is also increased at the proximity of the injection site of chemicals such as cobalt and cobalt-protoporphyrin-IX (cobalt-heme). Protoporphyrin-IX, the tetrapyrrole nucleus of type-b heme compounds, was ineffective in altering the enzyme activity in vivo. The developmental pattern of heme oxygenase in skin was compared to that of the enzyme in liver. The enzyme activity in both organs was greatest during the 1st postpartum wk and declined to adult levels after 2 wk. The physiological implications of the increased activity of skin heme oxygenase are discussed, and it is concluded that the activity of the hepatic heme oxygenase system and that of the skin are regulated by the same mechanism.

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