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3. P08-20 Cytotoxic effects of the SOD mimic MnTnHex-2-PyP5+ and its combination with cisplatin in non-small cell lung cancer cells

Author

Soares, R., primary, Manguinhas, R., additional, Costa, J.G., additional, Fernandes, A.S., additional, Saraiva, N., additional, Gil, N., additional, Rosell, R., additional, Camões, S.P., additional, Batinic-Haberle, I., additional, Spasojevic, I., additional, Castro, M., additional, Miranda, J.P., additional, de Pinho, P. Guedes, additional, and Oliveira, N.G., additional

Published
2022
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6. Lariat ether carboxylic acids as ionizable hosts in the second coordination sphere of the siderophore ferrioxamine B in chloroform

Author

Batinic-Haberle, I., Spasojevic, I., Jang, Y., Bartsch, R.A., and Crumbliss, A.L.

Subjects
Ethers -- Research, Coordination compounds -- Research, Carboxylic acids -- Analysis, Chemistry
Abstract

A secondary sphere complex is formed with the association of the cyclic cavity of a lariat ether with a protonated amine side chain of ferrioxamine B, a trivalent iron siderophore. A binary assembly is formed at pH conditions more basic than the dissociation constant of the carboxylic acid side chain from the lariat ether. The length of the side arm chain of the lariat ether influences the stability of the assembly.

Published
1998

7. MnSOD is implicated in accelerated wound healing upon Negative Pressure Wound Therapy (NPWT): A case in point for MnSOD mimetics as adjuvants for wound management

Author

Bellot, G., Dong, X., Lahiri, A., Sebastin, S., Batinic-Haberle, I., Pervaiz, Shazib, Puhaindran, M., Bellot, G., Dong, X., Lahiri, A., Sebastin, S., Batinic-Haberle, I., Pervaiz, Shazib, and Puhaindran, M.

Abstract

© 2018 The Authors Negative Pressure Wound Therapy (NPWT), a widely used modality in the management of surgical and trauma wounds, offers clear benefits over conventional wound healing strategies. Despite the wide-ranging effects ascribed to NPWT, the precise molecular mechanisms underlying the accelerated healing supported by NPWT remains poorly understood. Notably, cellular redox status-a product of the balance between cellular reactive oxygen species (ROS) production and anti-oxidant defense systems-plays an important role in wound healing and dysregulation of redox homeostasis has a profound effect on wound healing. Here we investigated potential links between the use of NPWT and the regulation of antioxidant mechanisms. Using patient samples and a rodent model of acute injury, we observed a significant accumulation of MnSOD protein as well as higher enzymatic activity in tissues upon NPWT. As a proof of concept and to outline the important role of SOD activity in wound healing, we replaced NPWT by the topical application of a MnSOD mimetic, Mn(III) meso-tetrakis(N-ethylpyridinium-2-yl)porphyrin (MnTE-2-PyP5+, MnE, BMX-010, AEOl10113) in the rodent model. We observed that MnE is a potent wound healing enhancer as it appears to facilitate the formation of new tissue within the wound bed and consequently advances wound closure by two days, compared to the non-treated animals. Taken together, these results show for the first time a link between NPWT and regulation of antioxidant mechanism through the maintenance of MnSOD activity. Additionally this discovery outlined the potential role of MnSOD mimetics as topical agents enhancing wound healing.

Published
2019

8. Supramolecular assembly formation of ferrioxamine B and its Al(III), Ga(III) and In(III) analogues with dicyclohexano-18-crown-6 in chloroform

Author

Spasojevic, I., Batinic-Haberle, I., Choo, P.L., and Crumbliss, A.L.

Subjects
Amines -- Research, Crown ethers -- Analysis, Electronic structure -- Analysis, Chemistry
Abstract

The molecular recognition of the terminal group of ferrioxamine B and its Al(III), Ga(III), Fe(III) and In(III) complexes by the crown ether dicyclohexano-18-crown-6 involves host-guest complex formation. A chloroform extraction reaction characterizes the molecular recognition and analyzes the influence of alkyl and hydroxamate substituent groups on the formation of host-guest complex.

Published
1994

9. First in Human Clinical Trial of a Metalloporphyrin Dual Radioprotectant and Radiosensitizer, BMX-001, in Newly Diagnosed High-Grade Glioma Undergoing Concurrent Chemoradiation

Author

Peters, K.B., primary, Kirkpatrick, J.P., additional, Batinic-Haberle, I., additional, Affronti, M.L., additional, Woodring, S., additional, Iden, D., additional, Lipp, E.S., additional, Boyd, K., additional, Healy, P., additional, Herndon, J., additional, Spasojevic, I., additional, Penchev, S., additional, Gad, S., additional, Silberstein, D., additional, Johnson, M.O., additional, Randazzo, D., additional, Desjardins, A., additional, Friedman, H.S., additional, Ashley, D.M., additional, and Crapo, J., additional

Published
2019
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10. Update on hypoxia-inducible factors and hydroxylases in oxygen regulatory pathways:from physiology to therapeutics

Author

Ratcliffe, P. (Peter), Koivunen, P. (Peppi), Myllyharju, J. (Johanna), Ragoussis, J. (Jiannis), Bovée, J. V. (Judith VMG), Batinic-Haberle, I. (Ines), Vinatier, C. (Claire), Trichet, V. (Valérie), Robriquet, F. (Florence), Oliver, L. (Lisa), Gardie, B. (Betty), Ratcliffe, P. (Peter), Koivunen, P. (Peppi), Myllyharju, J. (Johanna), Ragoussis, J. (Jiannis), Bovée, J. V. (Judith VMG), Batinic-Haberle, I. (Ines), Vinatier, C. (Claire), Trichet, V. (Valérie), Robriquet, F. (Florence), Oliver, L. (Lisa), and Gardie, B. (Betty)

Abstract

The “Hypoxia Nantes 2016” organized its second conference dedicated to the field of hypoxia research. This conference focused on “the role of hypoxia under physiological conditions as well as in cancer” and took place in Nantes, France, in October 6–7, 2016. The main objective of this conference was to bring together a large group of scientists from different spheres of hypoxia. Recent advances were presented and discussed around different topics: genomics, physiology, musculoskeletal, stem cells, microenvironment and cancer, and oxidative stress. This review summarizes the major highlights of the meeting.

Published
2017

12. Mechanistic insights into the cytotoxicity and genotoxicity induced by glycidamide in human mammary cells

Author

Bandarra, S., Fernandes, A. S., Magro, I., Guerreiro, P. S., Pingarilho, M., Churchwell, M. I., Gil, O. M., Batinic-Haberle, I., Gonçalves, S., Rueff, J., Miranda, J. P., Marques, M., Beland, F. A, Castro, M., Gaspar, J. F., and Oliveira, N. G.

Abstract

Acrylamide (AA) is a well-known industrial chemical classified as a probable human carcinogen. Benign and malignant tumours at different sites, including the mammary gland, have been reported in rodents exposed to AA. This xenobiotic is also formed in many carbohydrate-rich foods prepared at high temperatures. For this reason, AA is an issue of concern in terms of human cancer risk. The epoxide glycidamide (GA) is thought to be the ultimate genotoxic AA metabolite. Despite extensive experimental and epidemiological data focused on AA-induced breast cancer, there is still lack of information on the deleterious effects induced by GA in mammary cells. The work reported here addresses the characterisation and modulation of cytotoxicity, generation of reactive oxygen species, formation of micronuclei (MN) and quantification of specific GA-DNA adducts in human MCF10A epithelial cells exposed to GA. The results show that GA significantly induces MN, impairs cell proliferation kinetics and decreases cell viability at high concentrations by mechanisms not involving oxidative stress. KU55933, an inhibitor of ataxia telangiectasia mutated kinase, enhanced the cytotoxicity of GA (P < 0.05), supporting a role of this enzyme in regulating the repair of GA-induced DNA lesions. Moreover, even at low GA levels, N7-GA-Gua adducts were generated in a linear dose-response manner in MCF10A cells. These results confirm that human mammary cells are susceptible to GA toxicity and reinforce the need for additional studies to clarify the potential correlation between dietary AA exposure and breast cancer risk in human populations.

Published
2013

18. Mechanistic insights into the cytotoxicity and genotoxicity induced by glycidamide in human mammary cells

Author

Bandarra, S., primary, Fernandes, A. S., additional, Magro, I., additional, Guerreiro, P. S., additional, Pingarilho, M., additional, Churchwell, M. I., additional, Gil, O. M., additional, Batinic-Haberle, I., additional, Goncalves, S., additional, Rueff, J., additional, Miranda, J. P., additional, Marques, M. M., additional, Beland, F. A., additional, Castro, M., additional, Gaspar, J. F., additional, and Oliveira, N. G., additional

Published
2013
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27. Mn porphyrin-based SOD mimic, MnTnHex-2-PyP5+, and non-SOD mimic, MnTBAP3−, suppressed rat spinal cord ischemia/reperfusion injury via NF-κB pathways.

Author

Celic, T., Španjol, J., Bobinac, M., Tovmasyan, A., Vukelic, I., Reboucas, J. S., Batinic-Haberle, I., and Bobinac, D.

Subjects
MANGANESE porphyrins, OXIDATIVE stress, SUPEROXIDE dismutase, ISCHEMIA, REPERFUSION injury, NF-kappa B, ANTI-inflammatory agents, PREVENTION
Abstract

Herein we have demonstrated that both superoxide dismutase (SOD) mimic, cationic Mn(III) meso-tetrakis( N-n-hexylpyridinium-2-yl)porphyrin (MnTnHex-2-PyP5+), and non-SOD mimic, anionic Mn(III) meso-tetrakis(4-carboxylatophenyl)porphyrin (MnTBAP3−), protect against oxidative stress caused by spinal cord ischemia/reperfusion via suppression of nuclear factor kappa B (NF-κB) pro-inflammatory pathways. Earlier reports showed that Mn(III) N-alkylpyridylporphyrins were able to prevent the DNA binding of NF-κB in an aqueous system, whereas MnTBAP3− was not. Here, for the first time, in a complex in vivo system-animal model of spinal cord injury-a similar impact of MnTBAP3−, at a dose identical to that of MnTnHex-2-PyP5+, was demonstrated in NF-κB downregulation. Rats were treated subcutaneously at 1.5 mg/kg starting at 30 min before ischemia/reperfusion, and then every 12 h afterward for either 48 h or 7 days. The anti-inflammatory effects of both Mn porphyrins (MnPs) were demonstrated in the spinal cord tissue at both 48 h and 7 days. The downregulation of NF-κB, a major pro-inflammatory signaling protein regulating astrocyte activation, was detected and found to correlate well with the suppression of astrogliosis (as glial fibrillary acidic protein) by both MnPs. The markers of oxidative stress, lipid peroxidation and protein carbonyl formation, were significantly reduced by MnPs. The favorable impact of both MnPs on motor neurons (Tarlov score and inclined plane test) was assessed. No major changes in glutathione peroxidase- and SOD-like activities were demonstrated, which implies that none of the MnPs acted as SOD mimic. Increasing amount of data on the reactivity of MnTBAP3− with reactive nitrogen species (RNS) (.NO/HNO/ONOO−) suggests that RNS/MnTBAP3−-driven modification of NF-κB protein cysteines may be involved in its therapeutic effects. This differs from the therapeutic efficacy of MnTnHex-2-PyP5+ which presumably occurs via reactive oxygen species and relates to NF-κB thiol oxidation; the role of RNS cannot be excluded. [ABSTRACT FROM AUTHOR]

Published
2014
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28. 2688

Author

St. Clair, W., primary, Sun, Y., additional, St. Clair, D., additional, Batinic-Haberle, I., additional, Fang, F., additional, Kudrimoti, M., additional, Warren, G., additional, and Crooks, P., additional

Published
2006
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29. 2623

Author

Daroczi, B., primary, Kari, G., additional, Zengin, A.Y., additional, Chinnaiyan, P., additional, Batinic-Haberle, I., additional, Rodeck, U., additional, and Dicker, A.P., additional

Published
2006
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45. Catalytic Scavenging of Peroxynitrite by Isomeric Mn(III) N-Methylpyridylporphyrins in the Presence of Reductants

Author

Ferrer-Sueta, G., Batinic-Haberle, I., Spasojevic, I., Fridovich, I., and Radi, R.

Abstract

Three isomers of manganese(III) 5,10,15,20-tetrakis(N-methylpyridyl)porphyrin (MnTMPyP) were evaluated for their reaction with peroxynitrite. The Mn(III) complexes reacted with peroxynitrite anion with rate constants of 1.85 × 107, 3.82 × 106, and 4.33 × 106 M-1 s-1 at 37 °C for MnTM-2-PyP, MnTM-3-PyP, and MnTM-4-PyP, respectively, to yield the corresponding oxo−Mn(IV) complexes. Throughout the pH range from 5 to 8.5, MnTM-2-PyP reacted 5-fold faster than the other two isomers. The oxo−Mn(IV) complexes could in turn be reduced by glutathione, ascorbate, urate, or oxidize tyrosine. The rate constants for the reduction of the oxo−Mn(IV) complexes ranged from >107 M-1 s-1 for ascorbate to 103−104 M-1 s-1 for tyrosine and glutathione. Cyclic voltammetry experiments show that there is no significant difference in the E1/2 of the Mn(IV)/Mn(III) couple; thus, the differential reactivity of the three isomeric complexes is interpreted in terms of electrostatic and steric effects. Micromolar concentrations of MnTM-2-PyP compete well with millimolar CO2 at reacting with ONOO-, and it can even scavenge a fraction of the ONOOCO2- that is formed. By being rapidly oxidized by ONOO- and ONOOCO2- and reduced by antioxidants such as ascorbate, urate, and glutathione, these manganese porphyrins, and especially MnTM-2-PyP, can redirect the oxidative potential of peroxynitrite toward natural antioxidants, thus protecting more critical targets such as proteins and nucleic acids.

Published
1999

48. Method of obtaining gallium from aluminate solution by electrolysis

Author

Jelacic, C, Barišin, D., and Batinic-Haberle, I.

Abstract

Gallium is an increasingly important material in the fields of semiconductors and energy transfer. A prime source of gallium is the aluminate solution that remains after the purification of bauxite. The authors have sought a way of reclaiming gallium economically by electrolysis of a laboratory aluminate solution without having to use a cathode of mercury – an environmental pollutant. Cathodes of copper, indium, 70In–30Ga, Wood's alloy, and mercury (for comparison) were used with a wide range of anodes. The study accounted for the effects of electrode material, temperature, current density, and initial gallium concentration on the yield, energy consumption, and utilization of both current and electrode. The best results were obtained with indium or In–Ga cathodes and with platinum, Pt–Ti, or stainless steel anodes, at 75°C and a current density of ~100 Am-2. Electrolysis was more efficient the higher the gallium concentration, demonstrating that commercial–scale electrolysis of aluminate solution is unlikely to be economically viable without prior concentration of gallium.MST/305

Published
1986
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49. Update on hypoxia-inducible factors and hydroxylases in oxygen regulatory pathways: from physiology to therapeutics

Author

Ratcliffe, P, Koivunen, P, Myllyharju, J, Ragoussis, J, Bovée, JVMG, Batinic-Haberle, I, Vinatier, C, Trichet, V, Robriquet, F, Oliver, L, and Gardie, B

Subjects
Signalling & Oncogenes, Metabolism, Cell Biology, Biochemistry & Proteomics, 3. Good health
Abstract

The "Hypoxia Nantes 2016" organized its second conference dedicated to the field of hypoxia research. This conference focused on "the role of hypoxia under physiological conditions as well as in cancer" and took place in Nantes, France, in October 6-7, 2016. The main objective of this conference was to bring together a large group of scientists from different spheres of hypoxia. Recent advances were presented and discussed around different topics: genomics, physiology, musculoskeletal, stem cells, microenvironment and cancer, and oxidative stress. This review summarizes the major highlights of the meeting.

50. Proteomic analysis of radiation-induced changes in rat lung: Modulation by the superoxide dismutase mimetic MnTE-2-PyP(5+).

Author

Yakovlev VA, Rabender CS, Sankala H, Gauter-Fleckenstein B, Fleckenstein K, Batinic-Haberle I, Jackson I, Vujaskovic Z, Anscher MS, Mikkelsen RB, Graves PR, Yakovlev, Vasily A, Rabender, Christopher S, Sankala, Heidi, Gauter-Fleckenstein, Ben, Fleckenstein, Katharina, Batinic-Haberle, Ines, Jackson, Isabel, Vujaskovic, Zeljko, and Anscher, Mitchell S

Abstract

Purpose: To identify temporal changes in protein expression in the irradiated rat lung and generate putative mechanisms underlying the radioprotective effect of the manganese superoxide dismutase mimetic MnTE-2-PyP(5+).Methods and Materials: Female Fischer 344 rats were irradiated to the right hemithorax with a single dose of 28 Gy and killed from day 1 to 20 weeks after irradiation. Proteomic profiling was performed to identify proteins that underwent significant changes in abundance. Some irradiated rats were administered MnTE-2-PyP(5+) and changes in protein expression and phosphorylation determined at 6 weeks after irradiation.Results: Radiation induced a biphasic stress response in the lung, as shown by the induction of heme oxygenase 1 at 1-3 days and at 6-8 weeks after irradiation. At 6-8 weeks after irradiation, the down-regulation of proteins involved in cytoskeletal architecture (filamin A and talin), antioxidant defense (biliverdin reductase and peroxiredoxin II), and cell signaling (β-catenin, annexin II, and Rho-guanosine diphosphate dissociation inhibitor) was observed. Treatment with MnTE-2-PyP(5+) partially prevented the apparent degradation of filamin and talin, reduced the level of cleaved caspases 3 and 9, and promoted Akt phosphorylation as well as β-catenin expression.Conclusion: A significant down-regulation of proteins and an increase in protein markers of apoptosis were observed at the onset of lung injury in the irradiated rat lung. Treatment with MnTE-2-PyP(5+), which has been demonstrated to reduce lung injury from radiation, reduced apparent protein degradation and apoptosis indicators, suggesting that preservation of lung structural integrity and prevention of cell loss may underlie the radioprotective effect of this compound. [ABSTRACT FROM AUTHOR]

Published
2010
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