Weiss Reaction Research Articles

Reactive oxygen species and its effect on germination of seeds

Within the realm of plant biology, a sophisticated and intricate antioxidative system (AOS) exists to combat detrimental reactive species (RS), with a primary focus on reactive oxygen species (ROS). This intricate network functions to preserve cellular homeostasis. Originally, reactive oxygen species (ROS) were identified as harmful byproducts of aerobic metabolic processes. It is a review paper that descries ROS in brief along with its production, source, reactivity, functions and many more. At first it describes about peroxisomes that helps in production of H2O2 & O2- & Production of ROS in vivo & in vitro. Secondly it describes about its Source or origin i.e. from Mitochondria, Transition Metal Ions, ER etc and it also describes about its chemical properties & reactivity of different ROS i.e. H2O2, HO , O2- & HO2 in different ways including Haber- Weiss Reaction which are mentioned in details . We also report about the role of ROS in germination process and its functions. To conclude we have reviewed ROS and compiled in a manner which will altogether shed a new light on the roles of ROS in a plant species.

The oxidative damage of the Lagerstroemia indica chlorosis mutant gl1 involves in ferroptosis

Photooxidation is the major physiological performance of the Lagerstroemia indica chlorosis mutant gl1 under field conditions. The mechanisms of the progressive symptoms of oxidative damage from the lower older leaves to the upper mature leaves are complicated and still unclear. The aim of this work was to investigate the physiological mechanisms of oxidative stress from the perspective of the photosynthetic metabolites. The phytosynthetic metabolites of gl1 mutant changed significantly compared to wild type (WT) L. indica, such as by increasing phenolics, decreasing soluble sugar, protein and ascorbate, and redistributing antioxidant enzyme activities. The co-accumulation of phenolics and guaiacol-POD in gl1 mutant promote the removal of H2O2, as well the increase of phenoxyl radicals levels. Furthermore, the ion balance was significantly disturbed and Fe accumulated the most among these fluctuating nutrients in the leaves of gl1 mutant. The accumulated Fe was found neither in the chloroplasts nor in the cell wall of the leaves and became unshielded Fe, which favors the Fenton/Haber–Weiss reaction and stabilizes the phenoxyl radicals in metal complexation. The results suggested that the increase of phenolics and Fe accumulation were obviously involved in oxidative damage of gl1 mutant.

More than a duologue: In-depth insights into epitranscriptomics and ferroptosis.

Beyond transcription, RNA molecules are enzymatically modified to influence the biological functions of living organisms. The term “epitranscriptomics” describes the changes in RNA strands aside from altering the innate sequences. Modifications on adenosine (A) are the most widely characterized epitranscriptomic modification, including N6-methyladenosine (m6A), N1-methyladenosine (m1A), polyadenylation, and adenosine-to-inosine (A-to-I) RNA editing, and modifications on other nucleotides seem to be fewer, such as N7-methylguanosine (m7G), 5-methylcytosine (m5C), and pseudouridine (Ψ). These changes on the RNA strand surface, exclusively by their RNA-modifying proteins (RMPs), are reported in various biological phenomena, including programmed cell death (PCD). One necro-biological phenomenon that has been observed for long but has started to gain heed in recent years is “ferroptosis.” The phospholipid peroxidation by polyunsaturated-fatty-acid-containing-phospholipid hydroperoxyl (PLOOH) radicals destroys membrane integrity due to a series of mechanisms. The Fenton reaction, constituting the final Haber–Weiss reaction that is less recognized, collaboratively leading to the conversion of polyunsaturated fatty acid (PUFA) to PLOOH, is the etymological origin of ferroptosis. However, it is with increasing evidence that ferroptotic signaling is also intervened by epitranscriptomic modifications, although the truth is still ambiguous. We attempted to delineate some up-to-date discoveries on both epitranscriptomics and ferroptosis, bringing up the fundamentals to address any potential connection between the two. Next, we discussed whether a duologal relationship, or more, exists between the two, taking the ROS level and iron status into consideration. Lastly, we surveyed future perspectives that would favor the understanding of these topics.

Synthesis and Catalytic Property of Ribonucleoside-Derived Carbon Dots.

Exploring appropriate precursors has been proposed to be a promising strategy for the creation of artificial enzymes that are emerging as alternatives of natural enzymes. Herein, inspired by the catalytic activities of ribose nucleic acid, using ribonucleosides as precursors including adenosine, guanosine, cytidine, and uridine, respectively, four carbonic aggregates, namely, carbon dots (A-CDs, G-CDs, C-CDs, and U-CDs) to mimic artificial enzymes are synthesized. All the CDs show a planar graphene-like structure and thus can intercalatively bind with DNA double helix. Different from the other three CDs, the uridine-derived U-CDs exhibit unique catalytic property, which can mediate the topological transformation of DNA from supercoiled to nicked open-circular conformation. U-CDs can catalyze oxidation of O2 to generate singlet oxygen 1 O2 via a Haber-Weiss reaction, and consequently mediate oxidative cleavage of phosphate backbone in DNA and release the torsional energy stored in supercoiled DNA. Explorations reveal that the unique highly active oxygenated species, namely, quinone groups that are on the edge of U-CDs, play a key role in the catalytic production of 1 O2 . This work represents a new insight that using natural biomolecules in living systems as precursors can create new species beyond life.

A Novel Insight Into the Fate of Cardiomyocytes in Ischemia-Reperfusion Injury: From Iron Metabolism to Ferroptosis.

Ischemia-reperfusion injury (IRI), critically involved in the pathology of reperfusion therapy for myocardial infarction, is closely related to oxidative stress the inflammatory response, and disturbances in energy metabolism. Emerging evidence shows that metabolic imbalances of iron participate in the pathophysiological process of cardiomyocyte IRI [also termed as myocardial ischemia-reperfusion injury (MIRI)]. Iron is an essential mineral required for vital physiological functions, including cellular respiration, lipid and oxygen metabolism, and protein synthesis. Nevertheless, cardiomyocyte homeostasis and viability are inclined to be jeopardized by iron-induced toxicity under pathological conditions, which is defined as ferroptosis. Upon the occurrence of IRI, excessive iron is transported into cells that drive cardiomyocytes more vulnerable to ferroptosis by the accumulation of reactive oxygen species (ROS) through Fenton reaction and Haber–Weiss reaction. The increased ROS production in ferroptosis correspondingly leads cardiomyocytes to become more sensitive to oxidative stress under the exposure of excess iron. Therefore, ferroptosis might play an important role in the pathogenic progression of MIRI, and precisely targeting ferroptosis mechanisms may be a promising therapeutic option to revert myocardial remodeling. Notably, targeting inhibitors are expected to prevent MIRI deterioration by suppressing cardiomyocyte ferroptosis. Here, we review the pathophysiological alterations from iron homeostasis to ferroptosis together with potential pathways regarding ferroptosis secondary to cardiovascular IRI. We also provide a comprehensive analysis of ferroptosis inhibitors and initiators, as well as regulatory genes involved in the setting of MIRI.

Nanocapillary-Based Sensors for Detection of Copper Ions in Biological Systems

Copper performs a various biological function in living organisms. Dysregulation of copper ions can lead to unwanted redox reactions (Haber - Weiss reaction) caused by an increase in the free copper concentration or to its deposition in various organs (brain, kidney, eye cornea). Wilson’s, Menkes’s and Alzheimer’s disease are the most frequently mentioned diseases which associated with dysregulation of copper ions. These diseases are currently treatable only in the early stages. However, monitoring of the free copper concentration is extremely necessary.

Self‐Assembled Single‐Site Nanozyme for Tumor‐Specific Amplified Cascade Enzymatic Therapy

AbstractNanomaterials with enzyme‐mimicking activity (nanozymes) show potential for therapeutic interventions. However, it remains a formidable challenge to selectively kill tumor cells through enzymatic reactions, while leaving normal cells unharmed. Herein, we present a new strategy based on a single‐site cascade enzymatic reaction for tumor‐specific therapy that avoids off‐target toxicity to normal tissues. A copper hexacyanoferrate (Cu‐HCF) nanozyme with active single‐site copper exhibited cascade enzymatic activity within the tumor microenvironment: Tumor‐specific glutathione oxidase activity by the Cu‐HCF single‐site nanozymes (SSNEs) led to the depletion of intracellular glutathione and the conversion of single‐site CuII species into CuI for subsequent amplified peroxidase activity through a Fenton‐type Harber–Weiss reaction. In this way, abundant highly toxic hydroxyl radicals were generated for tumor cell apoptosis. The results show that SSNEs could amplify the tumor‐killing efficacy of reactive oxygen species and suppress tumor growth in vivo.

Enhanced antitumor effect via amplified oxidative stress by near-infrared light-responsive and folate-targeted nanoplatform

The efficiency of producing hydroxyl radicals (·OH) from hydrogen peroxide (H2O2) catalyzed by different iron compounds have been explored extensively. Exclusively, ferrocenecarboxylic acid (FCA) showed the best catalyzed activity for ·OH generation. Then, we designed and prepared near-infrared (NIR) light-responsive and folate-targeted nanoplatform, which co-delivered FCA, cisplatin and indocyanine green (ICG) for improving antitumor therapy through amplified oxidative stress. The noteworthy observation is that under the irradiation of NIR light, the lecithin structure could able to depolymerize through the photothermal conversion mechanism of encapsulated dye ICG, which has achieved an intelligent release of drugs. In addition, the released cisplatin is not only fully effective to damage the DNA of cancer cells but it is able to induce the production of intracellular H2O2, which could further be catalyzed by FCA to generate toxic ·OH for oxidative damage via Fenton and Haber–Weiss reaction. This original strategy may provide an efficient way for improved chemotherapy via amplified oxidative stress.

Differential interaction with O2 and N2 free-radicals, phytochemical fingerprinting and molecular docking reveals potent antioxidant activities of three major recreational foods of the Indian subcontinent

Leaves of Murraya koenigii (L.) Sprengel, Piper betle L. and Mentha spicata L. are primarily used for recreational-dietary purpose in the Indian subcontinent. The present study was aimed to evaluate their capacity to neutralize physiologically relevant free-radicals (O2 and N2 derived) through direct interaction, primarily focusing on the individual components of Haber–Weiss reaction and comprehensive evaluation of their antioxidant properties. The capacity to chelate ferrous iron and inhibit peroxidation of tissue lipid was reported as well. Dose-dependency against individual free-radicals were reflected by linearity measurements by Pearson’s coefficient, and inter-correlation patterns were studied by multivariate modelling. Several phytochemicals were identified using GC–MS and their interaction with antioxidant transcription factors (Nrf2 and FOXO) was studied through molecular docking and ADME profiling, reflecting potent bioactivities. The present study therefore, indicates that raw consumption of these dietary supplements would likely protect against free-radicals mediated oxidative stress.

Spin-Forbidden Branching in the Mechanism of the Intrinsic Haber-Weiss Reaction.

The mechanism of the O2 ⋅− and H2O2 reaction (Haber–Weiss) under solvent‐free conditions has been characterized at the DFT and CCSD(T) level of theory to account for the ease of this reaction in the gas phase and the formation of two different set of products (Blanksby et al., Angew. Chem. Int. Ed. 2007, 46, 4948). The reaction is shown to proceed through an electron‐transfer process from the superoxide anion to hydrogen peroxide, along two pathways. While the O3 ⋅− + H2O products are formed from a spin‐allowed reaction (on the doublet surface), the preferred products, O⋅−(H2O)+3O2, are formed through a spin‐forbidden reaction as a result of a favorable crossing point between the doublet and quartet surface. Plausible reasons for the preference toward the latter set are given in terms of the characteristics of the minimum energy crossing point (MECP) and the stability of an intermediate formed (after the MECP) in the quartet surface. These unique results show that these two pathways are associated with a bifurcation, yielding spin‐dependent products.

Effect of red cyst cell inoculation and iron(II) supplementation on autotrophic astaxanthin production by Haematococcus pluvialis under outdoor summer conditions

The negative effect of heat stress on the autotrophic astaxanthin production by Haematococcus pluvialis has been observed during outdoor culture in summer. Under the summer conditions, the proliferation of vegetative cells was highly halted in the green stage and the inducibility in the biosynthesis of astaxanthin was partly hindered in the red stage. Herein, under outdoor summer conditions in which variations of the diurnal temperature occur, heat-stress-driven inefficient vegetative growth of H. pluvialis was highly improved by inoculating the red cyst cells; thereby, maintaining relatively moderate intracellular carotenoid levels in the green stage. Subsequently, a remarkably enhanced astaxanthin titer was successfully obtained by supplementing 50μM iron(II) to induce the heat stress-driven Haber–Weiss reaction in the red stage. As a result, the productivity of astaxanthin in the cells cultured under summer temperature conditions (23.4–33.5°C) using the two methods of red cell (cyst) inoculation and the iron(Fe2+) supplementation was increased by 147% up to 5.53mg/L day compared with that of the cells cultured under spring temperature conditions (17.5–27.3°C). Our technical solutions will definitely improve the annual natural astaxanthin productivity in H. pluvialis in locations confronted by hot summer weather, particularly in large-scale closed photobioreactor systems.

Copper(II) complexes with new fluoroquinolones: Synthesis, structure, spectroscopic and theoretical study, DNA damage, cytotoxicity and antiviral activity

Copper(II) complexes with fluoroquinolones in the presence of the nitrogen donor heterocyclic ligands 1,10-phenanthroline have been considered in detail. The phenanthroline moiety was introduced into the ligand environment with the aim to determine whether the nuclease activity is feasible. All suitable X-ray structures of the complexes under study reveal a distorted square pyramidal coordination geometry for Cu(II) atom. The conformational and spectroscopic (FT-IR and UV–visible) behavior has been analyzed and has been interpreted with respect to B3LYP/6-311G* calculations including molecular dynamics. The ability of the complexes to cleave DNA was studied by agarose gel electrophoresis with plasmid DNA pBSK+. The results have confirmed that the complexes under study behave as the chemical nucleases. Nuclease like activity in the absence of hydrogen peroxide allows us to deduce an interaction of the complexes with the DNA resulting in the conversion of supercoiled circular DNA to the nicked form. The DNA cleavage activity enhanced by the presence of hydrogen peroxide demonstrates the participation of reactive oxygen species, such as superoxide radical anions and hydroxyl radicals which presence was confirmed independently using the standard radical scavenging agents. It has been suggested that the radical formation through the Fenton/Haber–Weiss reaction is mediated by the redox cycling mechanisms with the participation of cupric/cuprous ions. Cytotoxic activity was evaluated as the 50% cytotoxic concentration (CC50). The potential effects of tested compounds on replication of murine gammaherpesvirus 68 (MHV-68) under in vitro conditions were also evaluated. However, no antiviral activity against MHV-68 was observed.

Enhanced autotrophic astaxanthin production from Haematococcus pluvialis under high temperature via heat stress-driven Haber–Weiss reaction

High temperatures (30-36 °C) inhibited astaxanthin accumulation in Haematococcus pluvialis under photoautotrophic conditions. The depression of carotenogenesis was primarily attributed to excess intracellular less reactive oxygen species (LROS; O2 (-) and H2O2) levels generated under high temperature conditions. Here, we show that the heat stress-driven inefficient astaxanthin production was improved by accelerating the iron-catalyzed Haber-Weiss reaction to convert LROS into more reactive oxygen species (MROS; O2 and OH·), thereby facilitating lipid peroxidation. As a result, during 18 days of photoautotrophic induction, the astaxanthin concentration of cells cultured in high temperatures in the presence of iron (450 μM) was dramatically increased by 75 % (30 °C) and 133 % (36 °C) compared to that of cells exposed to heat stress alone. The heat stress-driven Haber-Weiss reaction will be useful for economically producing astaxanthin by reducing energy cost and enhancing photoautotrophic astaxanthin production, particularly outdoors utilizing natural solar radiation including heat and light for photo-induction of H. pluvialis.

Adrenaline and noradrenaline: protectors against oxidative stress or molecular targets?

Density functional theory was used to investigate the potential role of neurotransmitters adrenaline and noradrenaline regarding oxidative stress. It is predicted that they can be efficient as free radical scavengers both in lipid and aqueous media, with the main reaction mechanism being the hydrogen transfer and the sequential proton loss electron transfer, respectively. Despite the polarity of the environment, adrenaline and noradrenaline react with (•)OOH faster than Trolox, which suggests that they are better peroxyl radical scavengers than the reference compound. Both catecholamines are also proposed to be capable of efficiently inhibiting the oxidative stress induced by copper(II)-ascorbate mixtures, and the (•)OH production via Haber-Weiss reaction, albeit the effects on the later are only partial. They exert such beneficial effects by sequestering Cu(II) ions. In summary, these catecholamines can be capable of reducing oxidative stress, by scavenging free radicals and by sequestering metal ions. However, at the same time they might lose their functions in the process due to the associated structural modifications. Consequently, adrenaline and noradrenaline can be considered as both protectors and molecular targets of oxidative stress. Fortunately, under the proper conditions, both catecholamines can be regenerated to their original form so their functions are restored.

Melatonin and its metabolites as copper chelating agents and their role in inhibiting oxidative stress: a physicochemical analysis.

The copper sequestering ability of melatonin and its metabolites cyclic 3-hydroxymelatonin (3OHM), N(1) -acetyl-N(2) -formyl-5-methoxykynuramine (AFMK), and N(1) -acetyl-5-methoxykynuramine (AMK) was investigated within the frame of the Density Functional Theory. It was demonstrated that these compounds are capable of chelating copper ions, yielding stable complexes. The most likely chelation sites were identified. Two different mechanisms were modeled, the direct-chelation mechanism (DCM) and the coupled-deprotonation-chelation mechanism (CDCM). It is proposed that, under physiological conditions, CDCM would be the main chelation route for Cu(II). It was found that melatonin and its metabolites fully inhibited the oxidative stress induced by Cu(II)-ascorbate mixtures, via Cu(II) chelation. In the same way, melatonin, AFMK, and 3OHM also prevented the first step of the Haber-Weiss reaction, consequently turning off the ˙OH production via the Fenton reaction. Therefore, it is proposed that, in addition to the previously reported free radical scavenging cascade, melatonin is also involved in a concurrent 'chelating cascade', thereby contributing to a reduction in oxidative stress. 3OHM was identified as the most efficient of the studied compounds for that purpose, supporting the important role of this metabolite in the beneficial effects of melatonin against oxidative stress.

Non Transferrin Bound Iron: Nature, Manifestations and Analytical Approaches for Estimation

Iron is an essential trace element and plays a number of vital roles in biological system. It also leads the chains of pathological actions if present in excess and/or present in free form. Major portion of iron in circulation is associated with transferrin, a classical iron transporter, which prevent the existence of free iron. The fraction of iron which is free of transferrin is known as "non transferrin bound iron". Along with the incidence in iron over loaded patient non transferrin bound iron has been indicated in patients without iron overload. It has been suggested as cause as well as consequence in a number of pathological conditions. The major organs influenced by iron toxicity are heart, pancreas, kidney, organs involved in hematopoiesis etc. The most commonly suggested way for iron mediated pathogenesis is through increased oxidative stress and their secondary effects. Generation of free oxygen radicals by iron has been well documented in Fenton chemistry and Haber-Weiss reaction. Non transferrin bound iron has obvious chance to generate the free reactive radicals as it is not been shielded by the protective carrier protein apo transferrin. The nature of non transferrin bound iron is not clear at present time but it is definitely a group of heterogenous iron forms free from transferrin and ferritin. A variety of analytical approaches like colorimetry, chromatography, fluorimetry etc. have been experimented in different research laboratories for estimation of non transferrin bound iron. However the universally accepted gold standard method which can be operated in pathological laboratories is still to be developed.

Superparamagnetic iron oxide nanoparticles as radiosensitizer via enhanced reactive oxygen species formation

Internalization of citrate-coated and uncoated superparamagnetic iron oxide nanoparticles by human breast cancer (MCF-7) cells was verified by transmission electron microscopy imaging. Cytotoxicity studies employing metabolic and trypan blue assays manifested their excellent biocompatibility. The production of reactive oxygen species in iron oxide nanoparticle loaded MCF-7 cells was explained to originate from both, the release of iron ions and their catalytically active surfaces. Both initiate the Fenton and Haber–Weiss reaction. Additional oxidative stress caused by X-ray irradiation of MCF-7 cells was attributed to the increase of catalytically active iron oxide nanoparticle surfaces.

Comment on: Identification of antimicrobial activity among FDA-approved drugs for combating Mycobacterium abscessus and Mycobacterium chelonae

Sir, In the article titled ‘Identification of antimicrobial activity among FDA-approved drugs for combating Mycobacterium abscessus and Mycobacterium chelonae’ published in the July 2011 issue of JAC, it was reported that the FDA-approved drug metronidazole has potent activity (<0.015 mg/L; ∼87 nM) against the rapid-growing mycobacteria (RGM) Mycobacterium abscessus.1 This finding intrigued us and our clinical colleagues who treat M. abscessus-infected patients here at NIH. We therefore tried to repeat their experiment with M. abscessus ATCC 19977 and some recent patient isolates of M. abscessus to evaluate their susceptibility to metronidazole. We regret to report that we did not observe any MIC99, even at the highest concentration of the drug we tested (2 mM) after 48, 72 and 96 h. In accordance with the method published in the paper, we grew the M. abscessus ATCC 19977 (and four clinical isolates) from glycerol stock in 7H9 Middlebrook medium, passaged them once and let them grow to an OD650 of 0.2–0.4. The cell cultures were then diluted to an OD650 of 0.0002 in 7H9 medium and 50 μL of the cells was added to 50 μL of drug at various concentrations in a 96-well plate. They were incubated at 37°C for 48, 72 and 96 h and no killing of this RGM was observed (Figure 1a). Figure 1. (a) MICs of drugs for M. abscessus ATCC 19977 after 72 h. Each of the drugs was assayed in duplicate. MTZ, metronidazole. Each drug was serially diluted (50% each time) from well 1 to well 11, and well 12 does not have any drug. The concentration (in ... It is known that M. abscessus is susceptible to clarithromycin,2 and we therefore included this as a positive control in the experiment. PA-824, another nitroimidazole that is currently in Phase II clinical trials for the treatment of tuberculosis, has shown aerobic as well as anaerobic activity against the slow-growing mycobacteria Mycobacterium tuberculosis.3 It was also tested for activity against the RGM M. abscessus. The susceptibility of M. abscessus to clarithromycin clearly shows that there was no flaw in the experimental design, yet M. abscessus grew in the presence of 100 μM metronidazole and 50 μM PA-824 (Figure 1a). To investigate the susceptibility of M. abscessus ATCC 19977 and four clinical isolates to a higher concentration of metronidazole we determined the MIC99 starting with a 2 mM concentration of metronidazole, but we still did not observe any cidal effect of metronidazole even at such a high concentration (Figure 1b). In addition, no killing was observed with PA-824 at a concentration of 2 mM (data not shown). Strains tested have been identified as belonging to the M. abscessus group by partial sequencing of the secA gene4 and/or MALDI-TOF (matrix-assisted laser desorption ionization–time of flight) mass spectrometry.5 Metronidazole is known for its activity and has been used in the treatment of diseases caused by anaerobic microorganisms like Trichomonas vaginalis,6 Entamoeba histolytica7 and Clostridium difficile6 and microaerophilic bacteria like Helicobacter pylori.8 Though metronidazole is active against hypoxically adapted non-replicating M. tuberculosis, it is inactive against rapidly replicating M. tuberculosis under aerobic conditions.9 Metronidazole, which belongs to the class of 5-nitroimidazoles, has a single electron reduction potential of −0.4 to −0.5 V, which is out of the range normally accessible to the mammalian redox system. Under a limiting oxygen concentration in microbes the redox potential range is −0.42 V and lower and is suitable for the bioreductive activation of metronidazole. Upon single electron reduction of nitroimidazole, a nitro radical anion is produced,10 which could reduce oxygen in a microaerophilic organism to form superoxide.11 In the presence of transition elements like iron or copper, the hydrogen peroxide and superoxide react to form a hydroxyl radical by the Haber–Weiss reaction,10 causing inhibition of DNA synthesis and DNA strand breakage by this futile cycle. Metronidazole induces the expression of SOS response genes, which are responsible for DNA repair by the RecA pathway,10 as a result of which recA mutants in Escherichia coli and H. pylori are more susceptible to metronidazole treatment.12,13 Under normoxic conditions reduction of molecular oxygen by reduced metronidazole would be expected to render it harmless, as superoxide formed would be rapidly decomposed by the microbial superoxide dismutase.10 Our finding clearly demonstrates that metronidazole is inactive against M. abscessus under aerobic conditions, as has been reported. Metronidazole is potent against anaerobic organisms, but cannot be used in the treatment of infection with M. abscessus. Metronidazole does not kill RGM M. abscessus at a concentration of 2 mM (342.3 mg/L), which is more than 20 000-fold the concentration of what was reported by Chopra et al.1

Light-mediated interaction of methotrexate with transition metal Cu(II)

Methotrexate (MTX), an anticancer drug used for treatment of the malignancies is able to generate reactive oxygen species (ROS) upon illumination. Copper has been shown to be capable of mediating the action of several anticancer drugs through production of ROS. Present study is an attempt to characterize the MTX–Cu(II) interaction by spectroscopy. UV–visible and fluorescence spectra shown an enhancement in photoinduced oxidation of MTX when subjected to irradiation with Cu(II) as compared to MTX alone. This may be attributed to the interaction of MTX with Cu(II); which was further confirmed by fourier transform infrared (FTIR) spectroscopy. We have also demonstrated that MTX upon irradiation with white light caused oxidative damage to protein and DNA. This damage to protein and DNA got enhanced in presence of Cu(II). This is probably due to the enhanced generation of hydroxyl radical via Fenton/Haber–Weiss reaction. As Cu(I) is present bound to chromatin thus, when MTX is given as chemotherapeutic agent it possibly could mobilize endogenous Cu(I) and mediate killing of cancer cells through ROS generation.

An association between polymorphism of the heme oxygenase-1 and -2 genes and age-related macular degeneration

Iron may be implicated in the generation of oxidative stress by the catalyzing the Haber–Weiss or Fenton reaction. On the other hand, oxidative stress has been implicated in the pathogenesis of age-related macular degeneration (AMD) and heme oxygenase-1 (HO-1), encoded by the HMOX1 gene and heme oxygenase-2 (HO-2), encoded by the HMOX2 gene are important markers of iron-related oxidative stress and its consequences. Therefore, variability of the HMOX1 and HMOX2 genes might be implicated in the pathogenesis of AMD through the modulation of the cellular reaction to oxidative stress. In the present work, we investigated the association between AMD and a G → C transversion at the 19 position in the HMOX1 gene (the 19G>C-HMOX1 polymorphism, rs2071747) and a A → G transition at the −42 + 1444 position in the HMOX2 gene (the −42 + 1444A>G-HMOX2 polymorphism, rs2270363) and its modulation by some environmental factors. 279 patients with AMD and 105 controls were recruited in this study and the polymorphisms were typed by restriction fragment length polymorphism and allele-specific polymerase chain reaction (PCR). We observed an association between the occurrence of dry AMD and the G/A genotype of the −42 + 1444A>G-HMOX2 polymorphism (odds ratio (OR) 2.72), whereas the G/G genotype reduced the risk of dry AMD (OR 0.41). The G/C genotype and the C allele of the 19 G>C-HMOX1 polymorphism and the G/G genotype and the G allele of the −42 + 1444A>G-HMOX2 polymorphism were associated with progression of AMD from dry to wet form (OR 4.83, 5.20, 2.55, 1.69, respectively). On the other hand, the G/G genotype and the G allele of the 19 G>C-HMOX1 polymorphism and the A/G genotype and the A allele of the −42 + 1444A>G-HMOX2 polymorphism protected against AMD progression (OR 0.19, 0.19, 0.34, 0.59, respectively). Therefore, the 19G>C-HMOX1 and the −42 + 1444A>G-HMOX2 polymorphisms may be associated with the occurrence and progression of AMD.Electronic supplementary materialThe online version of this article (doi:10.1007/s11033-011-0955-3) contains supplementary material, which is available to authorized users.