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.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4324168 | PMC |
| http://dx.doi.org/10.1016/j.jpba.2014.11.044 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Pharmacological interventions for remifentanil-induced hyperalgesia: A systematic review and network meta-analysis of preclinical trials.
PLoS One
December 2024
Institute of Applied Health Sciences, Epidemiology Group, School of Medicine, Medical Sciences and Nutrition, University of Aberdeen, Aberdeen, United Kingdom.
Background: To improve perioperative pain management, several interventions have been suggested for the prevention of increased pain sensitivity caused by opioids (called opioid-induced hyperalgesia). It is currently unclear which intervention is the most effective or appropriate in preventing opioid-induced hyperalgesia. Remifentanil is the most investigated opioid causing opioid-induced hyperalgesia.
View Article and Find Full Text PDFExamination of diverse iron-chelating agents for the protection of differentiated PC12 cells against oxidative injury induced by 6-hydroxydopamine and dopamine.
Sci Rep
June 2022
Faculty of Pharmacy, Charles University, Akademika Heyrovského 1203, 500 05, Hradec Králové, Czech Republic.
Labile redox-active iron ions have been implicated in various neurodegenerative disorders, including the Parkinson's disease (PD). Iron chelation has been successfully used in clinical practice to manage iron overload in diseases such as thalassemia major; however, the use of conventional iron chelators in pathological states without systemic iron overload remains at the preclinical investigative level and is complicated by the risk of adverse outcomes due to systemic iron depletion. In this study, we examined three clinically-used chelators, namely, desferrioxamine, deferiprone and deferasirox and compared them with experimental agent salicylaldehyde isonicotinoyl hydrazone (SIH) and its boronate-masked prochelator BSIH for protection of differentiated PC12 cells against the toxicity of catecholamines 6-hydroxydopamine and dopamine and their oxidation products.
View Article and Find Full Text PDFDirect modulation of hepatocyte hepcidin signaling by iron.
World J Hepatol
October 2021
Center for Alcohol Research and Salem Medical Center, University of Heidelberg, Heidelberg 69121, Germany.
Background: Liver-secreted hepcidin is the systemic master switch of iron homeostasis and decreased levels of hepcidin are considered to cause iron overload not only in hereditary hemochromatosis but also in hemolytic anemia and chronic liver diseases. The regulation of hepcidin is complex and its response to iron is still not completely understood.
Aim: To study the direct effect of iron on various established hepcidin signaling pathways in hepatoma cells or primary hepatocytes.
The Labile Iron Pool Reacts Rapidly and Catalytically with Peroxynitrite.
Biomolecules
September 2021
Departamento de Química, Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto 14040-901, Brazil.
Article Synopsis
- The study found that removing the Labile Iron Pool (LIP) in macrophage cells increases oxidation levels, indicating that LIP normally reacts with peroxynitrite to reduce its oxidants.
- This discovery shifts the understanding of LIP's role in biochemistry and prompts further questions on its interaction with peroxynitrite.
- The follow-up research characterized this interaction, revealing it functions as a catalytic system with a specific reaction rate, suggesting LIP acts as a constant peroxynitrite reductase in these cells.
Siderophore-Assisted Dissolution of Iron(III) Hydroxide Oxides from Iron-Rich Fossil Matrices.
Chempluschem
August 2020
PANGEA Research Centre, School of Biological, Earth and Environmental Sciences, University of New South Wales, Sydney NSW, 2052, Australia.
Current paleontological techniques to separate vertebrate fossils from encasing iron-rich cements by chemical means are limited by the low solubility of common iron(III) hydroxide oxides such as hematite and goethite. This study examines novel geochemical extractions capable of selectively dissolving iron(III) hydroxide oxides, in aqueous solutions of pH 9-11, without damaging fossilised bones or teeth (hydroxidecarbonate-apatite). This involves the siderophore ligands pyridoxal isonicotinoyl hydrazone (PIH), salicylaldehyde isonicotinoyl hydrazone (SIH), and acetohydroxamic acid (aHA), whose coordination complexes with iron(III) show exceptionally high formation stability constants.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!