Kinetics of the reactions of nitrogen dioxide with glutathione,cysteine, and uric acid at physiological pH

Nitrogen dioxide (NO₂^•) is a key biological oxidant. It can be derived from peroxynitrite via the interaction of nitric oxide with superoxide, from nitrite with peroxidases, or from autoxidation of nitric oxide. In this study, submicromolar concentrations of NO₂^• were generated in < 1 μs using pulse radiolysis, and the kinetics of scavenging NO₂^• by glutathione, cysteine, or uric acid were monitored by spectrophotometry. The formation of the urate radical was observed directly, while the production of the oxidizing radical obtained on reaction of NO₂^• with the thiols (the thiyl radical) was monitored via oxidation of 2,2′-azino-bis-(3-ethylthiazoline-6-sulfonic acid). At pH 7.4, rate constants for reaction of NO₂^• with glutathione, cysteine, and urate were estimated as 2 × 10⁷, 5 × 10⁷, and 2 × 10⁷ M⁻¹ s⁻¹, respectively. The variation of these rate constants with pH indicated that thiolate reacted much faster than undissociated thiol. The dissociation of urate also accelerated reaction with NO₂^• at pH > 8. The thiyl radical from GSH reacted with urate with a rate constant of 3 × 10⁷ M⁻¹ s⁻¹. The implications of these values are: (i) the lifetime of NO₂^• in cytosol is < 10 μs; (ii) thiols are the dominant ‘sink’ for NO₂^• in cells/tissue, whereas urate is also a major scavenger in plasma; (iii) the diffusion distance of NO₂^• is 0.2 μm in the cytoplasm and < 0.8 μm in plasma; (iv) urate protects GSH against depletion on oxidative challenge from NO₂^•; and (v) reactions between NO₂^• and thiols/urate severely limit the likelihood of reaction of NO₂^• with NO• to form N₂O₃ in the cytoplasm.     

Clarification of the Relationship Between Free Radical Spin Trapping and Carbon Tetrachloride Metabolism in Microsomal Systems

It has been proposed that the C-phenyl-N-tert-butylnitrone/trichloromethyl radical adduct (PBN/^•CCl₃) is metabolized to either the C-phenyl-N-tert-butylnitrone/carbon dioxide anion radical adduct (PBN/^•CO₂⁻) or the glutathione (GSH) and CCl₄-dependent PBN radical adduct (PBN/[GSH-^•CCl₃]). Inclusion of PBN/^•CCl₃ in microsomal incubations containing GSH, nicotinamide adenine dinucleotide phosphate (NADPH), or GSH plus NADPH produced no electron spin resonance (ESR) spectral data indicative of the formation of either the PBN/[GSH-^•CCl₃] or PBN/^•CO₂⁻ radical adducts. Microsomes alone or with GSH had no effect on the PBN/^•CCl₃ radical adduct. Addition of NADPH to a microsomal system containing PBN/^•CCl₃ presumably reduced the radical adduct to its ESR-silent hydroxylamine because no ESR signal was observed. The Folch extract of this system produced an ESR spectrum that was a composite of two radicals, one of which had hyperfine coupling constants identical to those of PBN/^•CCl₃. We conclude that PBN/^•CCl₃ is not metabolized into either PBN/[GSH-^•CCl₃] or PBN/^•CO₂⁻ in microsomal systems.     

Increased levels of superoxide in brains from old female rats

Hypertension, aging and a range of neurodegenerative diseases are associated with increased oxidative damage. The present study examined whether superoxide (O₂^•-) levels in brain are increased during aging in female rats, and the role of superoxide dismutase (SOD) and oestrogen in regulating O₂^•- levels.

Young adult (3 month) and old (11 month) female spontaneously hypertensive stroke prone rats (SHRSP) and normotensive Wistar-Kyoto rats (WKY) were studied. O₂^•- levels were measured in brain homogenates by lucigenin chemiluminescence and SOD expression by Western blotting. Ageing significantly increased brain O₂^•- levels in WKY (cortex +216%, hippocampus +320%, striatum +225%) and to a greater extent in SHRSP (cortex +540%, hippocampus +580%, striatum +533%). Older SHRSP showed a decline in cortical Cu/Zn SOD expression compared to young adult SHRSP. Oestrogen did not attenuate O₂^•- levels.

The results show a significant age-dependent increase in brain O₂^•- levels which is exaggerated in SHRSP. The excess cortical O₂^•- levels in the SHRSP may be associated with a down-regulation of Cu/Zn SOD but are not related to a decrease in oestrogen.     

Aromatic trap analysis of free radicals production in experimental collagen-induced arthritis in the rat: protective effect of glycosaminoglycans treatment

Many findings demonstrated that Glycosaminoglycans (GAGs) and Proteoglycans (PGs) possess antioxidant activity. Collagen-induced arthritis (CIA) is an experimental animal model similar to human rheumatoid arthritis (RA) in which free radicals are involved. Sodium salicylate can be used as a chemical trap for hydroxyl radicals (OH •), the most damaging reactive oxygen species (ROS), yielding 2,5-dihydroxybenzoic acid), (2,5-DHBA) and 2,3-dihydroxybenzoic acid (2,3-DHBA). The measurement of these two acids in the plasma allows to indirectly assess the production of OH • radicals. The aim of the study was to investigate the effect of hyaluronic acid (HYA) (30 mg/kg i.p.) or chondroitin-4-sulphate (C4S) (30 mg/kg i.p.), on free radical production in Lewis rats subjected to CIA. After the immunization with bovine collagen type II in complete Freund's adjuvant, rats developed an erosive hind paw arthritis, that produced high plasma OH • levels assayed as 2,3-DHBA and 2,5-DHBA, primed lipid peroxidation, evaluated by analyzing conjugated dienes (CD) in the articular cartilage; decreased the concentration of endogenous vitamin E (VE) and catalase (CA) in the joint cartilage; enhanced macrophage inflammatory protein-2 (MIP-2) serum levels and increased elastase (ELA) evaluated as an index of activated leukocyte polymophonuclear (PMNs) accumulation in the articular joints. The administration of HYA and C4S starting at the onset of arthritis (day 11) for 20 days, limited inflammation and the clinical signs in the knee and paw, reduced OH • production, decreased CD levels, partially restored the endogenous antioxidants VE and CA, reduced MIP-2 serum levels and limited PMNs infiltration. The results indicate that the GAGs HYA and C4S significantly reduce free radical production in CIA and could be used as a tool to investigate the role of antioxidants in RA.     

Hydroxyl radical generation caused by the reaction of singlet oxygen with a spin trap, DMPO, increases significantly in the presence of biological reductants

Photosensitizers newly developed for photodynamic therapy of cancer need to be assessed using accurate methods of measuring reactive oxygen species (ROS). Little is known about the characteristics of the reaction of singlet oxygen (₁O₂) with spin traps, although this knowledge is necessary in electron spin resonance (ESR)/spin trapping. In the present study, we examined the effect of various reductants usually present in biological samples on the reaction of ₁O₂ with 5,5-dimethyl-1-pyrroline-N-oxide (DMPO). The ESR signal of the hydroxyl radical (•OH) adduct of DMPO (DMPO-OH) resulting from ₁O₂-dependent generation of •OH strengthened remarkably in the presence of reduced glutathione (GSH), 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid (Trolox), ascorbic acid, NADPH, etc. A similar increase was observed in the photosensitization of uroporphyrin (UP), rose bengal (RB) or methylene blue (MB). Use of 5-(diethoxyphosphoryl)-5-methyl-1-pyrroline-N-oxide (DEPMPO) as a spin trap significantly lessened the production of its •OH adduct (DEPMPO-OH) in the presence of the reductants. The addition of DMPO to the DEPMPO-spin trapping system remarkably increased the signal intensity of DEPMPO-OH. DMPO-mediated generation of •OH was also confirmed utilizing the hydroxylation of salicylic acid (SA). These results suggest that biological reductants enhance the ESR signal of DMPO-OH produced by DMPO-mediated generation of •OH from ₁O₂, and that spin trap-mediated •OH generation hardly occurs with DEPMPO.     

Photogeneration of free radicals (*OH and HB*-) and singlet oxygen (1O2) by hypocrellin B in TX-100 micelles microsurroundings

To solve the problems faced in clinical use of hypocrellins, a water-soluble preparation of Hypocrellin B (HB), HB-Triton X-100 (TX-100) micelles, was prepared. To evaluate the photodynamic activity, the free radicals (^•OH and HB^•¯) and singlet oxygen (

1

O

2

) generated via photosensitization of the preparation in aqueous solution were detected by using electron paramagnetic resonance (EPR) and spectrophotometric methods. It was observed that

1

O

2

was formed with a quantum yield of 0.72, similar to that for HB in organic solvents, further, hydroxyl radicals (

•

OH) could also be efficiently produced by the new preparation, which have never before been detected following HB photoactivities. In addition, the semiquinone anion radicals (HB^•-) could also be generated via the self-electron transfer between an excited triplet state and a ground state molecule. The accumulation of HB^•- would replace that of

•

OH or

1

O

2

with the depletion of oxygen in the system. All these findings suggested that the HB-TX-100 micelles could play the photodynamic action through not only the type I mechanism by free radicals (^•OH, O₂^•- and HB^•-) but also the type II mechanism by singlet oxygen (

1

O

2

). It can be concluded further that the new preparation basically maintains the inherent photodynamic activity of HB, or even higher.     

Oral Microbiota,a Potential Determinant for the Treatment Efficacy of Gastric Helicobacter Pylori Eradication in Humans

The oral cavity serves as another reservoir for gastric Helicobacter pylori and may contribute to the failure of gastric H. pylori eradication therapy. However, changes to the oral microbial composition after gastric H. pylori eradication therapy has not yet been identified. This study aims to dissect whether the oral microbiota is involved and which bacterium mediates the clinic failure in H. pylori eradication. In the present study, the oral microorganisms from patients who had received the gastric H. pylori eradication treatment were analyzed by a high-throughput 16S rRNA deep sequencing. We found that the β diversity and composition of oral microbiota were remarkably changed in the patients who had experienced successful gastric H. pylori eradication treatment (SE group) compared to the failure group (FE group). Significantly enriched families, including Prevotellaceae, Streptococcaceae, Caulobacteraceae, and Lactobacillaceae, were detected in the SE group. In contrast, the bacterial families, such as Weeksellaceae, Neisseriaceae, Peptostreptococcaceae, Spirochaetaceae, and Veillonellaceae, were abundantly expressed in the FE group. Five operational taxonomic units (OTUs) were positively correlated with DOB values, while two OTUs exhibited negative trends. These different enriched OTUs were extensively involved in the 20 metabolic pathways. These results suggest that a balanced environment in the oral microbiota contributes to H. pylori eradication and metabolic homeostasis in humans. Our data demonstrated that the changes in oral microbiota might contribute to the therapeutic effects of antibiotic therapy. Therefore, a different therapy on the detrimental oral microbiota will increase the therapeutic efficacy of antibiotics on H. pylori infection. Open in a separate window     

Thermal stability of triple helical DNAs containing 2'-deoxyinosine and 2'-deoxyxanthosine

In this paper, we describe the synthesis and thermal stabilities of the triplexes containing either 2′-deoxyinosine (1) or 2′-deoxyxanthosine (3) in their second strands. It was found that the triplexes with the 2′-deoxy-5-methylcytidine(dM)•1:dC and dM•1:dA base triplets are thermally stable, but those containing the dM•1:T and dM•1:dG base triplets are unstable under both neutral and slightly acidic conditions. On the other hand, it was found that the oligonucleotide containing 3 could form thermally stable triplexes with the oligonucleotides that involve four natural bases opposite the sites of 3. The rank of the thermal stabilities of the triplexes was as follows: the triplex containing the dM•3:dC base triplet > that containing the dM•3:dA base triplet > that containing the dM•3:T base triplet > that containing the dM•3:dG base triplet.     

Mitochondrial superoxide production during oxalate-mediated oxidative stress in renal epithelial cells

Crystals of calcium oxalate monohydrate (COM) in the renal tubule form the basis of most kidney stones. Tubular dysfunction resulting from COM-cell interactions occurs by mechanism(s) that are incompletely understood. We examined the production of reactive oxygen intermediates (ROI) by proximal (LLC-PK1) and distal (MDCK) tubular epithelial cells after treatment with COM (25–250 μg/ml) to determine whether ROI, specifically superoxide (O₂^•−), production was activated, and whether it was sufficient to induce oxidative stress. Employing inhibitors of cytosolic and mitochondrial systems, the source of ROI production was investigated. In addition, intracellular glutathione (total and oxidized), energy status (ATP), and NADH were measured. COM treatment for 1–24 h increased O₂^•− production 3–6-fold as measured by both lucigenin chemiluminescence in permeabilized cells and dihydrorhodamine fluorescence in intact cells. Using selective inhibitors we found no evidence of cytosolic production. The use of mitochondrial probes, substrates, and inhibitors indicated that increased O₂^•− production originated from mitochondria. Treatment with COM decreased glutathione (total and redox state), indicating a sustained oxidative insult. An increase in NADH in COM-treated cells suggested this cofactor could be responsible for elevating O₂^•− generation. In conclusion, COM increased mitochondrial O₂^•− production by epithelial cells, with a subsequent depletion of antioxidant status. These changes may contribute to the reported cellular transformations during the development of renal calculi.     

Hyperphagia in offsprings of in utero hyperglycemic mothers is associated with increased expression of heparan sulfate proteoglycans in hypothalamus

In utero hyperglycemia has consequences on future outcomes in the offsprings. We had earlier shown that in utero hyperglycemia impacts proteoglycans/glycosaminoglycans, one of the key molecules involved in brain development. Hypothalamic HSPGs such as syndecan-1 and syndecan-3 are well known for their involvement in feeding behavior. Therefore, studies were carried out to determine the effect of maternal hyperglycemia on the expression of HSPGs in the hypothalamus of offspring brain. Results revealed increased protein abundance of Syndecan-1 and -3 as well as glypican-1 in postnatal adults from hyperglycemic mothers. This was associated with increased hyperphagia and increased expression of Neuropeptide Y. These results indicate the likely consequences on offsprings exposed to in utero hyperglycemia on its growth.

Graphical abstract

     

Mast cells in allergy and beyond

Mast cells (MC) are highly granulated tissue dwelling cells, widely distributed throughout the body in connective tissues and on mucosal surfaces. They are derived from bone marrow progenitors that migrate into the blood and subsequently into the tissues, where they undergo final maturation. Mast cell proliferation, differentiation, survival and activation are regulated by stem cell factor, the ligand for the c-kit tyrosine kinase receptor, expressed on the mast cell surface. They release a large number of pro-inflammatory and immunoregulatory mediators after activation induced by either immunoglobulin E-dependent or immunoglobulin E-independent mechanisms. Mast cells have been most widely studied in the context of allergic reactions and parasite infections, but there is now compelling evidences that they are important players in innate and acquired immunity, wound healing, fibrosis, tumors and autoimmune diseases. This review will discuss current advances in these fields.Cell facts

• Mast cells are high affinity IgE receptor bearing tissue dwelling cells containing prominent cytoplasmic granules and key cells in allergy.

• Mast cell proliferation, differentiation, survival and activation are regulated by stem cell factor.

• Mast cells and their mediators participate in innate and acquired immunity, wound healing, tissue remodeling, angiogenesis and autoimmune diseases.

     

Expressed Salmonella antigens within macrophages enhance the proliferation of CD4+ and CD8+ T lymphocytes by means of bystander dendritic cells

ATP-dependent Lon protease-deficient Salmonella enterica serovar Typhimurium (strain CS2022) appeared to invade successfully the mesenteric lymph nodes (MLN) and Peyer's patches (PP) of BALB/c mice and appeared to be easily eradicated by the host after oral immunization. As detected by flow cytometry, the population of major histocompatibility complex class I (MHC-I)-expressing macrophages and dendritic cells (DCs) was increased in the PP of mice immunized with CS2022 on day 6 after immunization. Thereafter, the population of splenic surface CD69(+) T lymphocytes prepared from mice immunized with CS2022 6 weeks prior to measurement increased as a result of the administration of the extracellular vesicles of RAW264.7 macrophage-like cells derived by Salmonella challenge. In addition, the proliferation of CD8(+) and even of CD4(+)T cells isolated from mouse spleens immunized with CS2022 was enhanced after cocultivation with naive DCs in the presence of the extracellular vesicles. These findings indicate that the extracellular vesicles prepared from the Salmonella-challenged macrophages carried salmonellae antigens to bystander DCs, thereby stimulating T-cell responses. Therefore, as antigen presentation after phagocytosis should be a central process in the T-cell activation that occurs in response to Salmonella infection, an oral immunization with CS2022 sufficiently induces T cell-mediated immunity in mice.     

Contribution of changes in demography and in the risk factors to the predicted pattern of cancer mortality among Spanish women by 2022

BackgroundChanges in the burden of cancer mortality are expected to be observed among Spanish women. We predict those changes, in Spain, for breast cancer (BC), colorectal cancer (CRC), lung cancer (LC) and pancreatic cancer (PC) from 2013 to 2022.MethodsBayesian age–period–cohort modeling was used to perform projections of the cancer burden in 2013–2022, extrapolating the trend of cancer mortality data from 1998 to 2012. We assessed the time trends of the crude rates (CRs) during 1998–2012, and compared the number of cancer deaths between the periods 2008–2012 and 2018–2022 to assess the contribution of demographic changes and changes in the risk factors for cancer.ResultsDuring 1998–2012, CRs of cancer decreased for BC (0.3% per year) and increased for LC (4.7%), PC (2%) and CRC (0.7%). During 2013–2022, CRs might level off for CRC, whereas the time trends for the remaining cancers might continue at a similar pace. During 2018–2022, BC could be surpassed by CRC as the most frequent cause of cancer mortality among Spanish women, whereas LC could be the most common cause of cancer mortality among women aged 50–69 years (N/year = 1960 for BC versus N/year = 1981 for LC). Comparing 2018–2022 and 1998–2012, changes in the risk factors for cancer could contribute 37.93% and 18.36% to the burden of LC and PC, respectively, and demographic shifts – mainly due to ageing (19.27%) – will drive the burden of CRC.ConclusionsDuring 2018–2022, demographic changes (ageing) and changes in risk factors could have a different impact on the lifetime risk of cancer among Spanish women.     

Identification of the hydroxyl radical and other reactive oxygen species in human neutrophil granulocytes exposed to a fragment of the amyloid beta peptide

A fragment of the amyloid beta protein, βA(25-35), was investigated for its effect on production of reactive oxygen species (ROS) in human neutrophil granulocytes. The formation and identification of ROS were examined by using a 2',7'-dichlorofluorescin (DCF) fluorescence assay, a luminol chemiluminescence assay, electron paramagnetic resonance (EPR) spectroscopy with DEPMPO as a spin trap, and hydroxylation of 4-hydroxybenzoate (4-HBA). The DCF assay showed that βA(25-35) stimulated formation of ROS in a concentration and time dependent manner. The inverted peptide, βA(35-25), gave no response. Also, luminol-amplified chemiluminescence was stimulated by βA(25-35). Incubation with diethyldithiocarbamate (a superoxide dimustase inhibitor) and salicylhydroxamate (SHA; a myeloperoxidase inhibitor) reduced the chemiluminescence. This indicates that hypochlorous acid (HOCl) is formed after exposure to βA(25-35). The EPR spectra indicated a concentration dependent formation of superoxide ( O 2 • - ) - and hydroxyl ( •OH)- radicals. Hydroxylation of 4-HBA to 3,4,-dihydroxybenzoate confirmed production of •OH. This response was attenuated by SHA, indicating involvement of HOCl in formation of •OH. The DCF fluorescence was inhibited with U0126 (an extracellular signal regulated protein kinase (ERK) inhibitor). Further analysis with western blot confirmed phosphorylation of ERK1/2 after exposure to βA(25-35). The phospholipase A 2 (PLA 2 ) inhibitor 7,7-dimethyl-(5Z,8Z)-eicosadienoic acid, and diphenyleneiodonium, which inhibits the NADPH oxidase, also led to a reduction of the DCF fluorescence. The present findings indicate that βA(25-35) stimulates the NADPH oxidase by activating the ERK pathway and PLA 2 . Production of O 2 • - can lead to HOCl and further formation of •OH, which both have a cytotoxic potential.     

To what end does nature produce superoxide? NADPH oxidase as an autocrine modifier of membrane phospholipids generating paracrine lipid messengers

Production of superoxide anion O2<sup>••- by the membrane-bound enzyme NADPH oxidase of phagocytes is a long-known phenomenon; it is generally assumed that O2• kill bacterial intruders. The details and the chemistry of the killing process have, however, remained a mystery. Isoforms of NADPH oxidase exist in membranes of nearly every cell, suggesting that reactive oxygen species (ROS) participate in intra- and intercellular signaling processes. What the nature of the signal is exactly, how it is transmitted, and what structural characteristics a receptor of a "radical message" must have, have not been addressed convincingly. This review discusses how the action of messengers is in agreement with radical-specific behavior.

In search for the smallest common denominator of cellular free radical activity we hypothesize that O2•e acid, HO2&bull under primordial conditions as regulators of membrane mechanics and that isoprostanes, widely used markers of "oxidative stress", may be an adventitious correlate of this biologic activity of O2•location="post" arrange="compact">2&bullre is presented that suggests that O2•location="post" arrange="compact">2&bullfying cell membranes, help other agents gain access to the hydrophobic region of phospholipid bilayers and hence contribute to lipid-dependent signaling cascades. With this, O2•location="post" arrange="compact">2&bullndispensable adjuvants for the generation of cellular signals, for membrane transport, channel gating and hence, in a global sense, for cell viability and growth. We also suggest that many of the allegedly O2•ial pathologies and carcinogenic derailments are due to membrane-modifying activity rather than other chemical reactions of O2•location="post" arrange="compact">2&bull this picture is the potential evolution of the "radical theory of ageing" to a "lipid theory of aging".</sup>     

The EU Biocidal Products Directive and the consequences for Dinsinfectants

The title of my presentation suggests or at least anticipates that the EU legislative process, to provide a harmonised regulatory platform for biocides in the EU, has been finalised when this symposium takes place.When adapted and subsequently implemented in the EU member states (estimation Q3 1999), this directive will have a major impact on the market of disinfectants for both the suppliers of active substances and formulators supplying disinfectant products to customers and consumers. This presentation will focus on (technical) regulatory consequences rather than economical or business effects.

• • scope: which products will fall under the regime of this directive, which are excluded?

• • principle: one product—one authorization and mutual recognition; lead times involved?

• • procedure: how will the simplified procedures foreseen (hopefully) help the disinfectant supplier?

• • data requirements: why do the dossier requirements for products and particularly actives need to be so excessively costly and what is the role of risk assessment?

• • transitional arrangements: what can and can't disinfectant suppliers do to keep their products on the market or to introduce new products?

• • review programme: what will happen to the availability of active substances?

The directive itself will not give sufficiient answers to all issues mentioned above to allow a harmonised interpretation across the EU. A number of technical guidance documents is therefore being developed covering Common Principles, Data Requirements and Conditions to include an Active Substance on Annex I. The workability of the whole directive will very much be dependent on the practical details to be dealt with in these documents.Disinfectant suppliers also do recognize the merits of the directive (improved protection of man and the environment, harmonisation across EU, etc.), provided however that it does not undermine the efforts of our industry to deliver better hygiene with safe, effective but also affordable disinfectants.     

浙江鹿城发现云开脊蛇和黄家岭脊蛇

2022年9月和2023年4月在浙江省温州市鹿城区仰义水库分别采集到1条脊蛇属（Achalinus）物种幼体尸体标本（标本编号分别为2022AZJLCN1和2023AZJLCN2）。形态上它们分别与黄家岭脊蛇（A. huangjietangi）和云开脊蛇（A. yunkaiensis）接近。基于线粒体COI基因片段的最大似然树结果,两蛇样本序列分别与这两种脊蛇聚为一个支系;2023AZJLCN2标本与云开脊蛇的遗传距离为0.10,低于中国境内分布脊蛇属物种间的遗传距离（0.12～0.16）;2022AZJLCN1标本与黄家岭脊蛇的遗传距离为0.09,在黄家岭脊蛇种内遗传距离（0.04～0.12）范围内。综上,鉴定2023AZJLCN2标本为云开脊蛇,2022AZJLCN1标本为黄家岭脊蛇。此前记录云开脊蛇分布于我国广东和广西,本次在浙江温州市鹿城区的发现为浙江蛇类新分布记录种;黄家岭脊蛇分布于安徽和浙江,此次在在温州市鹿城区的发现是温州市首次新分布记录。这两种脊蛇的新分布记录提示它们有更广的分布范围。     

Transgenic Mice With Elevated Level of CuZnSOD Are Highly Susceptible to Malaria Infection

Copper/zinc superoxide dismutase (CuZnSOD) catalyses the conversion of O₂^•− into H₂O₂. Constitutive overexpression of CuZnSOD in cells and animals creates an indigenous oxidative stress that predisposes them to added insults. In this study, we used transgenic CuZnSOD (Tg-CuZnSOD) mice with elevated levels of CuZnSOD to determine whether overexpression of CuZnSOD affected the susceptibility of these mice to plasmodium infection. Acute malaria is associated with oxidative stress, mediated by redox-active iron released from the infected RBC. Two independently derived Tg-CuZnSOD lines showed higher sensitivity than control mice to infection by Plasmodium berghei (P. berghei), reflected by an earlier onset and increased rate of mortality. Nevertheless, while Tg-CuZnSOD mice were more vulnerable than control mice, the levels of parasitemia were comparable in both strains. Moreover, treatment of infected red blood cells (RBC) with oxidative stress inducers, such as ascorbate or paraquat, reduced the viability of parasites equally in both transgenic and control RBC. This further confirms that increased CuZnSOD does not support plasmodia development. The data are consistent with the possibility that the combination of increased redox-active iron and elevated H₂O₂ in the plasmodium-infected Tg-CuZnSOD mice, led to an enhanced Fenton’s reaction-mediated HO^• production, and the resulting oxidative injury renders the transgenic mice more vulnerable to parasite infection.