Catecholamines may undergo iron-promoted oxidation resulting in formation of reactive intermediates (aminochromes) capable of redox cycling and reactive oxygen species (ROS) formation. Both of them induce oxidative stress resulting in cellular damage and death. Iron chelation has been recently shown as a suitable tool of cardioprotection with considerable potential to protect cardiac cells against catecholamine-induced cardiotoxicity. However, prolonged exposure of cells to classical chelators may interfere with physiological iron homeostasis. Prochelators represent a more advanced approach to decrease oxidative injury by forming a chelating agent only under the disease-specific conditions associated with oxidative stress. Novel prochelator (lacking any iron chelating properties) BHAPI [(E)-Ń-(1-(2-((4-(4,4,5,5-tetramethyl-1,2,3-dioxoborolan-2-yl)benzyl)oxy)phenyl)ethylidene) isonicotinohydrazide] is converted by ROS to active chelator HAPI with strong iron binding capacity that efficiently inhibits iron-catalyzed hydroxyl radical generation. Our results confirmed redox activity of oxidation products of catecholamines isoprenaline and epinephrine, that were able to activate BHAPI to HAPI that chelates iron ions inside H9c2 cardiomyoblasts. Both HAPI and BHAPI were able to efficiently protect the cells against intracellular ROS formation, depletion of reduced glutathione and toxicity induced by catecholamines and their oxidation products. Hence, both HAPI and BHAPI have shown considerable potential to protect cardiac cells by both inhibition of deleterious catecholamine oxidation to reactive intermediates and prevention of ROS-mediated cardiotoxicity.

• Keywords
• BHAPI, Cardiotoxicity, Catecholamines, HAPI, Iron chelation, Prochelator,
• MeSH
• Epinephrine antagonists & inhibitors   toxicity   MeSH
• Biocatalysis MeSH
• Cell Line MeSH
• Iron Chelating Agents pharmacology   MeSH
• Glutathione metabolism   MeSH
• Hydroxyl Radical metabolism   MeSH
• Isoproterenol antagonists & inhibitors   toxicity   MeSH
• Cardiotonic Agents pharmacology   MeSH
• Catecholamines antagonists & inhibitors   toxicity   MeSH
• Rats MeSH
• Boronic Acids pharmacology   MeSH
• Humans MeSH
• Membrane Potential, Mitochondrial drug effects   MeSH
• Oxidative Stress drug effects   MeSH
• Prodrugs pharmacology   MeSH
• Reactive Oxygen Species metabolism   MeSH
• Semicarbazones pharmacology   MeSH
• Boron Compounds pharmacology   MeSH
• Iron chemistry   MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Epinephrine MeSH
• Iron Chelating Agents MeSH
• Glutathione MeSH
• Hydroxyl Radical MeSH
• Isoproterenol MeSH
• Cardiotonic Agents MeSH
• Catecholamines MeSH
• Boronic Acids MeSH
• N'-(1-(2-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzyloxy)phenyl)ethylidene)isonicotinohydrazide MeSH Browser
• Prodrugs MeSH
• Reactive Oxygen Species MeSH
• Semicarbazones MeSH
• Boron Compounds MeSH
• Iron MeSH

Free cellular iron catalyzes the formation of toxic hydroxyl radicals and therefore chelation of iron could be a promising therapeutic approach in pathological states associated with oxidative stress. Salicylaldehyde isonicotinoyl hydrazone (SIH) is a strong intracellular iron chelator with well documented potential to protect against oxidative damage both in vitro and in vivo. Due to the short biological half-life of SIH and risk of toxicity due to iron depletion, boronate prochelator BSIH has been designed. BSIH cannot bind iron until it is activated by certain reactive oxygen species to active chelator SIH. The aim of this study was to examine the toxicity and cytoprotective potential of BSIH, SIH, and their decomposition products against hydrogen peroxide-induced injury of H9c2 cardiomyoblast cells. Using HPLC, we observed that salicylaldehyde was the main decomposition products of SIH and BSIH, although a small amount of salicylic acid was also detected. In the case of BSIH, the concentration of formed salicylaldehyde consistently exceeded that of SIH. Isoniazid and salicylic acid were not toxic nor did they provide any antioxidant protective effect in H9c2 cells. In contrast, salicylaldehyde was able to chelate intracellular iron and significantly preserve cellular viability and mitochondrial inner membrane potential induced by hydrogen peroxide. However it was consistently less effective than SIH. The inherent toxicities of salicylaldehyde and SIH were similar. Hence, although SIH - the active chelating agent formed following the BSIH activation - undergoes rapid hydrolysis, its principal decomposition product salicylaldehyde accounts markedly for both cytoprotective and toxic properties.

• Keywords
• Boronyl salicylaldehyde isonicotinoyl hydrazone (BSIH), Iron chelation, Prochelator, Salicylaldehyde, Salicylaldehyde isonicotinoyl hydrazone (SIH),
• MeSH
• Aldehydes pharmacology   toxicity   MeSH
• Cell Line MeSH
• Iron Chelating Agents pharmacology   toxicity   MeSH
• Hydrazones pharmacology   toxicity   MeSH
• Rats MeSH
• Boronic Acids pharmacology   toxicity   MeSH
• Isonicotinic Acids pharmacology   toxicity   MeSH
• Membrane Potential, Mitochondrial drug effects   MeSH
• Myoblasts, Cardiac drug effects   metabolism   MeSH
• Oxidative Stress drug effects   MeSH
• Hydrogen Peroxide toxicity   MeSH
• Half-Life MeSH
• Reactive Oxygen Species metabolism   MeSH
• Cell Survival drug effects   MeSH
• Chromatography, High Pressure Liquid MeSH
• Iron metabolism   MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Research Support, N.I.H., Extramural MeSH
• Names of Substances
• (isonicotinic acid (2-(4,4,5,5-tetramethyl-(1,3,2)dioxaborolan-2-yl)benzylidene)hydrazide) MeSH Browser
• Aldehydes MeSH
• Iron Chelating Agents MeSH
• Hydrazones MeSH
• Boronic Acids MeSH
• Isonicotinic Acids MeSH
• Hydrogen Peroxide MeSH
• Reactive Oxygen Species MeSH
• salicylaldehyde isonicotinoyl hydrazone MeSH Browser
• Iron MeSH

Salicylaldehyde isonicotinoyl hydrazone (SIH) is an intracellular iron chelator with well documented potential to protect against oxidative injury both in vitro and in vivo. However, it suffers from short biological half-life caused by fast hydrolysis of the hydrazone bond. Recently, a concept of boronate prochelators has been introduced as a strategy that might overcome these limitations. This study presents two complementary analytical methods for detecting the prochelator-boronyl salicylaldehyde isonicotinoyl hydrazone-BSIH along with its active metal-binding chelator SIH in different solution matrices and concentration ranges. An LC-UV method for determination of BSIH and SIH in buffer and cell culture medium was validated over concentrations of 7-115 and 4-115 μM, respectively, and applied to BSIH activation experiments in vitro. An LC-MS assay was validated for quantification of BSIH and SIH in plasma over the concentration range of 0.06-23 and 0.24-23 μM, respectively, and applied to stability studies in plasma in vitro as well as analysis of plasma taken after i.v. administration of BSIH to rats. A Zorbax-RP bonus column and mobile phases containing either phosphate buffer with EDTA or ammonium formate and methanol/acetonitrile mixture provided suitable conditions for the LC-UV and LC-MS analysis, respectively. Samples were diluted or precipitated with methanol prior to analysis. These separative analytical techniques establish the first validated protocols to investigate BSIH activation by hydrogen peroxide in multiple matrices, directly compare the stabilities of the prochelator and its chelator in plasma, and provide the first basic pharmacokinetic data of this prochelator. Experiments reveal that BSIH is stable in all media tested and is partially converted to SIH by H2O2. The observed integrity of BSIH in plasma samples from the in vivo study suggests that the concept of prochelation might be a promising strategy for further development of aroylhydrazone cytoprotective agents.

• Keywords
• Aroylhydrazone, Boronyl salicylaldehyde isonicotinoyl hydrazone, Pharmacokinetics, Prochelator salicylaldehyde isonicotinoyl hydrazone, Stability,
• MeSH
• Aldehydes analysis   blood   MeSH
• Chelating Agents analysis   MeSH
• Chromatography, Liquid methods   MeSH
• Mass Spectrometry methods   MeSH
• Hydrazones analysis   blood   MeSH
• Culture Media chemistry   MeSH
• Boronic Acids analysis   blood   MeSH
• Isonicotinic Acids analysis   blood   MeSH
• Molecular Structure MeSH
• Rats, Wistar MeSH
• Reference Standards MeSH
• Sensitivity and Specificity MeSH
• Spectrophotometry, Ultraviolet methods   MeSH
• Drug Stability MeSH
• Animals MeSH
• Check Tag
• Male MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Research Support, N.I.H., Extramural MeSH
• Names of Substances
• (isonicotinic acid (2-(4,4,5,5-tetramethyl-(1,3,2)dioxaborolan-2-yl)benzylidene)hydrazide) MeSH Browser
• Aldehydes MeSH
• Chelating Agents MeSH
• Hydrazones MeSH
• Culture Media MeSH
• Boronic Acids MeSH
• Isonicotinic Acids MeSH
• salicylaldehyde isonicotinoyl hydrazone MeSH Browser

Salicylaldehyde isonicotinoyl hydrazone (SIH) is a lipophilic, tridentate iron chelator with marked anti-oxidant and modest cytotoxic activity against neoplastic cells. However, it has poor stability in an aqueous environment due to the rapid hydrolysis of its hydrazone bond. In this study, we synthesized a series of new SIH analogs (based on previously described aromatic ketones with improved hydrolytic stability). Their structure-activity relationships were assessed with respect to their stability in plasma, iron chelation efficacy, redox effects and cytotoxic activity against MCF-7 breast adenocarcinoma cells. Furthermore, studies assessed the cytotoxicity of these chelators and their ability to afford protection against hydrogen peroxide-induced oxidative injury in H9c2 cardiomyoblasts. The ligands with a reduced hydrazone bond, or the presence of bulky alkyl substituents near the hydrazone bond, showed severely limited biological activity. The introduction of a bromine substituent increased ligand-induced cytotoxicity to both cancer cells and H9c2 cardiomyoblasts. A similar effect was observed when the phenolic ring was exchanged with pyridine (i.e., changing the ligating site from O, N, O to N, N, O), which led to pro-oxidative effects. In contrast, compounds with long, flexible alkyl chains adjacent to the hydrazone bond exhibited specific cytotoxic effects against MCF-7 breast adenocarcinoma cells and low toxicity against H9c2 cardiomyoblasts. Hence, this study highlights important structure-activity relationships and provides insight into the further development of aroylhydrazone iron chelators with more potent and selective anti-neoplastic effects.

• MeSH
• Aldehydes chemistry   pharmacology   toxicity   MeSH
• Antioxidants chemistry   pharmacology   MeSH
• Antineoplastic Agents chemistry   toxicity   MeSH
• Cell Line MeSH
• Iron Chelating Agents chemistry   pharmacology   MeSH
• Hydrazones chemistry   pharmacology   toxicity   MeSH
• Humans MeSH
• MCF-7 Cells MeSH
• Myoblasts drug effects   MeSH
• Oxidative Stress drug effects   MeSH
• Hydrogen Peroxide toxicity   MeSH
• Structure-Activity Relationship MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Aldehydes MeSH
• Antioxidants MeSH
• Antineoplastic Agents MeSH
• Iron Chelating Agents MeSH
• Hydrazones MeSH
• Hydrogen Peroxide MeSH
• salicylaldehyde isonicotinoyl hydrazone MeSH Browser

Oxidative stress is a common denominator of numerous cardiovascular disorders. Free cellular iron catalyzes the formation of highly toxic hydroxyl radicals, and iron chelation may thus be an effective therapeutic approach. However, using classical iron chelators in diseases without iron overload poses risks that necessitate more advanced approaches, such as prochelators that are activated to chelate iron only under disease-specific oxidative stress conditions. In this study, three cell-membrane-permeable iron chelators (clinically used deferasirox and experimental SIH and HAPI) and five boronate-masked prochelator analogs were evaluated for their ability to protect cardiac cells against oxidative injury induced by hydrogen peroxide. Whereas the deferasirox-derived agents TIP and TRA-IMM displayed negligible protection and even considerable toxicity, the aroylhydrazone prochelators BHAPI and BSIH-PD provided significant cytoprotection and displayed lower toxicity after prolonged cellular exposure compared to their parent chelators HAPI and SIH, respectively. Overall, the most favorable properties in terms of protective efficiency and low inherent cytotoxicity were observed with the aroylhydrazone prochelator BSIH. BSIH efficiently protected both H9c2 rat cardiomyoblast-derived cells and isolated primary rat cardiomyocytes against hydrogen peroxide-induced mitochondrial and lysosomal dysregulation and cell death. At the same time, BSIH was nontoxic at concentrations up to its solubility limit (600 μM) and in 72-h incubation. Hence, BSIH merits further investigation for prevention and/or treatment of cardiovascular disorders associated with a known (or presumed) component of oxidative stress.

• Keywords
• BSIH, Deferasirox, Free radicals, ICL670A, Iron chelation, Prochelator, Salicylaldehyde isonicotinoyl hydrazone,
• MeSH
• Aldehydes chemistry   pharmacology   MeSH
• Apoptosis drug effects   MeSH
• Benzoates chemistry   pharmacology   MeSH
• Cell Line MeSH
• Iron Chelating Agents chemistry   pharmacology   MeSH
• Cytoprotection * MeSH
• Deferasirox MeSH
• Hydrazones chemistry   pharmacology   MeSH
• Myocytes, Cardiac drug effects   physiology   MeSH
• Rats MeSH
• Boronic Acids chemistry   pharmacology   MeSH
• Isonicotinic Acids chemistry   pharmacology   MeSH
• Membrane Potential, Mitochondrial drug effects   MeSH
• Oxidative Stress drug effects   MeSH
• Cell Membrane Permeability drug effects   MeSH
• Hydrogen Peroxide metabolism   MeSH
• Rats, Wistar MeSH
• Semicarbazones chemistry   pharmacology   MeSH
• Boron Compounds chemistry   pharmacology   MeSH
• Mitochondria, Heart drug effects   physiology   MeSH
• Triazoles chemistry   pharmacology   MeSH
• Iron chemistry   metabolism   MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Research Support, N.I.H., Extramural MeSH
• Comparative Study MeSH
• Names of Substances
• (isonicotinic acid (2-(4,4,5,5-tetramethyl-(1,3,2)dioxaborolan-2-yl)benzylidene)hydrazide) MeSH Browser
• Aldehydes MeSH
• Benzoates MeSH
• Iron Chelating Agents MeSH
• Deferasirox MeSH
• Hydrazones MeSH
• Boronic Acids MeSH
• Isonicotinic Acids MeSH
• N'-(1-(2-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzyloxy)phenyl)ethylidene)isonicotinohydrazide MeSH Browser
• Hydrogen Peroxide MeSH
• salicylaldehyde isonicotinoyl hydrazone MeSH Browser
• Semicarbazones MeSH
• Boron Compounds MeSH
• Triazoles MeSH
• Iron MeSH

SIGNIFICANCE: Anthracyclines (doxorubicin, daunorubicin, or epirubicin) rank among the most effective anticancer drugs, but their clinical usefulness is hampered by the risk of cardiotoxicity. The most feared are the chronic forms of cardiotoxicity, characterized by irreversible cardiac damage and congestive heart failure. Although the pathogenesis of anthracycline cardiotoxicity seems to be complex, the pivotal role has been traditionally attributed to the iron-mediated formation of reactive oxygen species (ROS). In clinics, the bisdioxopiperazine agent dexrazoxane (ICRF-187) reduces the risk of anthracycline cardiotoxicity without a significant effect on response to chemotherapy. The prevailing concept describes dexrazoxane as a prodrug undergoing bioactivation to an iron-chelating agent ADR-925, which may inhibit anthracycline-induced ROS formation and oxidative damage to cardiomyocytes. RECENT ADVANCES: A considerable body of evidence points to mitochondria as the key targets for anthracycline cardiotoxicity, and therefore it could be also crucial for effective cardioprotection. Numerous antioxidants and several iron chelators have been tested in vitro and in vivo with variable outcomes. None of these compounds have matched or even surpassed the effectiveness of dexrazoxane in chronic anthracycline cardiotoxicity settings, despite being stronger chelators and/or antioxidants. CRITICAL ISSUES: The interpretation of many findings is complicated by the heterogeneity of experimental models and frequent employment of acute high-dose treatments with limited translatability to clinical practice. FUTURE DIRECTIONS: Dexrazoxane may be the key to the enigma of anthracycline cardiotoxicity, and therefore it warrants further investigation, including the search for alternative/complementary modes of cardioprotective action beyond simple iron chelation.

• MeSH
• Antioxidants chemistry   pharmacology   MeSH
• Antineoplastic Agents adverse effects   chemistry   pharmacology   MeSH
• Anthracyclines adverse effects   chemistry   pharmacology   MeSH
• Chelating Agents adverse effects   chemistry   pharmacology   MeSH
• Cardiotonic Agents adverse effects   chemistry   pharmacology   MeSH
• Metals adverse effects   MeSH
• Humans MeSH
• Myocardium metabolism   MeSH
• Oxidation-Reduction MeSH
• Oxidative Stress * MeSH
• Razoxane adverse effects   chemistry   pharmacology   MeSH
• Reactive Oxygen Species metabolism   MeSH
• Signal Transduction * MeSH
• Heart drug effects   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Review MeSH
• Names of Substances
• Antioxidants MeSH
• Antineoplastic Agents MeSH
• Anthracyclines MeSH
• Chelating Agents MeSH
• Cardiotonic Agents MeSH
• Metals MeSH
• Razoxane MeSH
• Reactive Oxygen Species MeSH

BACKGROUND AND PURPOSE: The clinical utility of anthracycline antineoplastic drugs is limited by the risk of cardiotoxicity, which has been traditionally attributed to iron-mediated production of reactive oxygen species (ROS). EXPERIMENTAL APPROACH: The aims of this study were to examine the strongly lipophilic iron chelator, salicylaldehyde isonicotinoyl hydrazone (SIH), for its ability to protect rat isolated cardiomyocytes against the toxicity of daunorubicin (DAU) and to investigate the effects of SIH on DAU-induced inhibition of proliferation in a leukaemic cell line. Cell toxicity was measured by release of lactate dehydrogenase and staining with Hoechst 33342 or propidium iodide and lipid peroxidation by malonaldehyde formation. KEY RESULTS: SIH fully protected cardiomyocytes against model oxidative injury induced by hydrogen peroxide exposure. SIH also significantly but only partially and with no apparent dose-dependency, reduced DAU-induced cardiomyocyte death. However, the observed protection was not accompanied by decreased lipid peroxidation. In the HL-60 acute promyelocytic leukaemia cell line, SIH did not blunt the antiproliferative efficacy of DAU. Instead, at concentrations that reduced DAU toxicity to cardiomyocytes, SIH enhanced the tumoricidal action of DAU. CONCLUSIONS AND IMPLICATIONS: This study demonstrates that iron is most likely involved in anthracycline cardiotoxicity and that iron chelation has protective potential, but apparently through mechanism(s) other than by inhibition of ROS-induced injury. In addition to cardioprotection, iron chelation may have considerable potential to improve the therapeutic action of anthracyclines by enhancing their anticancer efficiency and this potential warrants further investigation.

• MeSH
• Leukemia, Promyelocytic, Acute metabolism   pathology   MeSH
• Aldehydes pharmacology   MeSH
• Antibiotics, Antineoplastic toxicity   MeSH
• Time Factors MeSH
• Iron Chelating Agents pharmacology   MeSH
• Cytoprotection MeSH
• Daunorubicin toxicity   MeSH
• HL-60 Cells MeSH
• Hydrazones pharmacology   MeSH
• Myocytes, Cardiac drug effects   metabolism   pathology   MeSH
• Rats MeSH
• Humans MeSH
• Malondialdehyde metabolism   MeSH
• Animals, Newborn MeSH
• Oxidative Stress drug effects   MeSH
• Lipid Peroxidation drug effects   MeSH
• Rats, Wistar MeSH
• Cell Proliferation drug effects   MeSH
• Cell Survival drug effects   MeSH
• Dose-Response Relationship, Drug MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Aldehydes MeSH
• Antibiotics, Antineoplastic MeSH
• Iron Chelating Agents MeSH
• Daunorubicin MeSH
• Hydrazones MeSH
• Malondialdehyde MeSH
• salicylaldehyde isonicotinoyl hydrazone MeSH Browser

BACKGROUND AND PURPOSE: The anticancer drugs doxorubicin and bleomycin are well-known for their oxidative stress-mediated side effects in heart and lung, respectively. It is frequently suggested that iron is involved in doxorubicin and bleomycin toxicity. We set out to elucidate whether iron chelation prevents the oxidative stress-mediated toxicity of doxorubicin and bleomycin and whether it affects their antiproliferative/proapoptotic effects. EXPERIMENTAL APPROACH: Cell culture experiments were performed in A549 cells. Formation of hydroxyl radicals was measured in vitro by electron paramagnetic resonance (EPR). We investigated interactions between five iron chelators and the oxidative stress-inducing agents (doxorubicin, bleomycin and H(2)O(2)) by quantifying oxidative stress and cellular damage as TBARS formation, glutathione (GSH) consumption and lactic dehydrogenase (LDH) leakage. The antitumour/proapoptotic effects of doxorubicin and bleomycin were assessed by cell proliferation and caspase-3 activity assay. KEY RESULTS: All the tested chelators, except for monohydroxyethylrutoside (monoHER), prevented hydroxyl radical formation induced by H(2)O(2)/Fe(2+) in EPR studies. However, only salicylaldehyde isonicotinoyl hydrazone and deferoxamine protected intact A549 cells against H(2)O(2)/Fe(2+). Conversely, the chelators that decreased doxorubicin and bleomycin-induced oxidative stress and cellular damage (dexrazoxane, monoHER) were not able to protect against H(2)O(2)/Fe(2+). CONCLUSIONS AND IMPLICATIONS: We have shown that the ability to chelate iron as such is not the sole determinant of a compound protecting against doxorubicin or bleomycin-induced cytotoxicity. Our data challenge the putative role of iron and hydroxyl radicals in the oxidative stress-mediated cytotoxicity of doxorubicin and bleomycin and have implications for the development of new compounds to protects against this toxicity.

• MeSH
• Aldehydes pharmacology   MeSH
• Antibiotics, Antineoplastic toxicity   MeSH
• Apoptosis drug effects   MeSH
• Bleomycin toxicity   MeSH
• Time Factors MeSH
• Iron Chelating Agents chemistry   pharmacology   MeSH
• Deferoxamine pharmacology   MeSH
• Doxorubicin toxicity   MeSH
• Electron Spin Resonance Spectroscopy MeSH
• Hydrazones pharmacology   MeSH
• Isoniazid analogs & derivatives   pharmacology   MeSH
• Humans MeSH
• Cell Line, Tumor MeSH
• Lung Neoplasms metabolism   pathology   MeSH
• Oxidative Stress drug effects   MeSH
• Hydrogen Peroxide chemistry   MeSH
• Lipid Peroxidation drug effects   MeSH
• Cell Proliferation drug effects   MeSH
• Pyridoxal analogs & derivatives   pharmacology   MeSH
• Razoxane pharmacology   MeSH
• Iron Compounds chemistry   metabolism   MeSH
• Cell Survival drug effects   MeSH
• Free Radicals chemistry   MeSH
• Iron chemistry   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Aldehydes MeSH
• Antibiotics, Antineoplastic MeSH
• Bleomycin MeSH
• Iron Chelating Agents MeSH
• Deferoxamine MeSH
• Doxorubicin MeSH
• Fenton's reagent MeSH Browser
• Hydrazones MeSH
• Isoniazid MeSH
• Hydrogen Peroxide MeSH
• pyridoxal isonicotinoyl hydrazone MeSH Browser
• Pyridoxal MeSH
• Razoxane MeSH
• salicylaldehyde isonicotinoyl hydrazone MeSH Browser
• Iron Compounds MeSH
• Free Radicals MeSH
• Iron MeSH