Role Of Peroxidation Research Articles

Role of Hydrogen Peroxide in Propofol Restoration of Microvascular Function Impaired by High Glucose

The University of Hong Kong, Hong Kong SAR, China. zhengyuan_xia@yahoo.comTo the Editor:— I read with great interest the recently published article by Nakahata et al. ,1“Propofol Restores Brain Microvascular Function Impaired by High Glucose via the Decrease in Oxidative Stress.” In this study, the authors observed that propofol, at potentially clinically relevant concentrations, dose-dependently attenuated or abolished rat brain microvascular dysfunction induced by high glucose, and that the protection of propofol, similar to that of the superoxide dismutase mimetic Tempol, is attributable to its inhibition of superoxide production induced by high glucose. Further, the authors found that nicotinamide adenine dinucleotide phosphate oxidase, but not xanthine oxidase, is the major source of superoxide production in the brain microvascular arteriolar wall after high glucose stimulation.1This is an interesting finding because nicotinamide adenine dinucleotide phosphate oxidase has also be reported as a major source of superoxide production in the diabetic heart2that is complicated by hypertrophic cardiomyopathy in the rat.3Therefore, theoretically, propofol may provide protection against oxidative injury of the diabetic heart through superoxide scavenging.I congratulate Nakahata et al. for the interesting and detailed results about the role of superoxide scavenging in propofol restoration of microvascular function impaired by high glucose.However, I think that the study design of Nakahata et al. 1should be debated. Oxidative stress results from an imbalance between the formation and neutralization of pro-oxidants (such as superoxide and hydrogen peroxide). Pathologic processes (such as high glucose or diabetes) disrupt this balance by increasing the formation of prooxidant in proportion to the available antioxidants (such as the intracellular antioxidant enzymes: superoxide dismutase and glutathione peroxidase) and subsequently result in oxidative injury (oxidative stress). Therefore, a more suitable title for the study of Nakahata et al. 1would be “Propofol Restores Brain Microvascular Function Impaired by High Glucose via the Decrease in Superoxide Production,” given that parameters that reflect oxidative damages were not measured in the study.High glucose has been shown to decrease intracellular levels of glutathione,4a potent endogenous antioxidant that converts hydrogen peroxide (H2O2) to water (H2O) catalyzed by glutathione peroxidase (i.e. , 2GSH + H2O2→ GSSG + 2H2O, where GSSG represents glutathione disulfide). Acute high glucose5as well as chronic hyperglycemia6can significantly increase the production of tumor necrosis factor (TNF)-α in humans. TNF-α in turn has been shown to cause significant human vascular endothelial cell apoptotic death, accompanied by more profound decreases in intracellular glutathione peroxidase activity (approximately 50% reduction vs. control) than in superoxide dismutase activity (approximately 30% reduction vs. control).7As such, a small dose of hydrogen peroxide can significantly augment TNF-α cellular toxicity, which can be attenuated by treatment with propofol.7Propofol has been shown to attenuate hydrogen peroxide–induced myocardial dysfunction in rats.8Of interest, we recently found that TNF-α (at 40 ng/ml) caused more profound increases in intracellular hydrogen peroxide (approximately 20-fold) than in superoxide (approximately 16-fold) in cultured human umbilical vein endothelial cells as measured by dihydroethidium and dichlorofluorescein fluorescence straining, respectively, and that abolishment of the increase of hydrogen peroxide but not the superoxide overproduction prevented TNF-α cellular toxicity (Fang Wang, M.D., M.Sc., Zhengyuan Xia, M.D., Ph.D., Jingping Quyang, M.D., Wuhan, Hubei, China, unpublished observation, April 2007).I am surprised that hydrogen peroxide production was not measured in the study of Nakahata et al. 1Furthermore, I propose that attenuation of hydrogen peroxide–mediated oxidative injury could be the major mechanism by which propofol restores brain microvascular function impaired by high glucose.The University of Hong Kong, Hong Kong SAR, China. zhengyuan_xia@yahoo.com

Role of hydrogen peroxide in competition and cooperation between Streptococcus gordonii and Actinomyces naeslundii.

In dental plaque alpha-haemolytic streptococci, including Streptococcus gordonii, are considered beneficial for oral health. These organisms produce hydrogen peroxide (H(2)O(2)) at concentrations sufficient to kill many oral bacteria. Streptococci do not produce catalase yet tolerate H(2)O(2). We recently demonstrated that coaggregation with Actinomyces naeslundii stabilizes arginine biosynthesis in S. gordonii. Protein arginine residues are sensitive to oxidation by H(2)O(2). Here, the ability of A. naeslundii to protect S. gordonii against self-produced H(2)O(2) was investigated. Coaggregation with A. naeslundii enabled S. gordonii to grow in the absence of arginine, and promoted survival of S. gordonii following growth with or without added arginine. Arginine-replete S. gordonii monocultures contained 20-30 microM H(2)O(2) throughout exponential growth. Actinomyces naeslundii did not produce H(2)O(2) but synthesized catalase, removed H(2)O(2) from coaggregate cultures and decreased protein oxidation in S. gordonii. On solid medium, S. gordonii inhibited growth of A. naeslundii; exogenous catalase overcame this inhibition. In coaggregate cultures, A. naeslundii cell numbers were >90% lower than in monocultures after 24 h. These results indicate that coaggregation with A. naeslundii protects S. gordonii from oxidative damage. However, high cell densities of S. gordonii inhibit A. naeslundii. Therefore, H(2)O(2) may drive these organisms towards an ecologically balanced community in natural dental plaque.

Role of hydrogen peroxide and Pharmaplant-turbo against cucumber powdery mildew fungus under organic and inorganic production

Cucumber leaves have been sprayed with a solution of hydrogen peroxide (H202) or Pharmaplant-turbo combined with organic or inorganic fertilizers under plasic house. Under the influence of H202, leaves exhibited resistant against Podoshaera fusca fungus, the causal agent of cucumber powdery mildew. H202 (15 mM) was able to decrease the disease severity from 90.4% to 12% in two experiments conducted in two seasons. Pharmaplant-turbo (Turbo) is new chemical compound and used as an antifungal compound. Turbo in 1 ml/L was able to decrease the disease severity from 90.4% to 11.5% in the both experiments as well. Both of H202 and Turbo were combined with organic treatment (compost + compost tea + seaweed extracts) which showed significant effect against cucumber powdery mildew fungus and strongly suppressed it as compared to control leaves. Organic treatment produced higher vegetative growth characters and greater early and total yields as compared to inorganic treatment, also organic fruits produced the lower nitrate content and the higher ascorbic acid content as compared to inorganic fruits. Our study have indicated that, H202 and Turbo combined with organic fertilizers play a role in the resistance of cucumber against powdery mildew by decreasing the disease severity. We suggest to give more attention to the direct application of H202 in low concentration and Turbo against powdery mildew diseases and other plant diseases.

Role of Hydrogen Peroxide in a Selected Emulsified Fuel Ratio and Comparing It to Diesel Fuel

In this present work, investigations are carried out to study the performance and emission characteristics of adding hydrogen peroxide (H2O2) as an additive with the selected ratio of the emulsifie...

Transient inhibitory effect of methoxychlor on testicular steroidogenesis in rat: an in vivo study

Methoxychlor, an organochlorine pesticide, has been reported to induce reproductive abnormalities in male reproductive tract. To get more insight into the mechanism(s) of gonadal toxicity provoked by methoxychlor, we investigated whether treatment with methoxychlor at low observed adverse effect level (LOAEL) would alter the activities of steroidogenic enzymes such as Delta(5)3beta-hydroxysteroid dehydrogenase (3beta-HSD) and Delta(5)17beta-hydroxysteroid dehydrogenase (17beta-HSD), the expression levels of steroidogenic acute regulatory (StAR) protein and androgen binding protein (ABP) in the testis of adult male rats. The experimental rats were exposed to a single dose of methoxychlor (50 mg/kg body weight) orally. The rats were killed at 0, 3, 6, 12, 24 and 72 h following treatment using anesthetic ether and testes were collected, processed and used to measure the activities of 3beta-HSD, 17beta-HSD, levels of hydrogen peroxide produced and the expression levels of StAR protein, and ABP. Methoxychlor administration resulted in a sequential reduction in the expression of StAR protein and activities of 3beta-HSD, 17beta-HSD with concomitant increase in the levels of hydrogen peroxide in the testis. These changes were significant between 6-12 h following treatment. The levels of ABP declined at 6-12 h following exposure to methoxychlor. The present study demonstrates transient effect of methoxychlor at LOAEL on testicular steroidogenesis and the possible role of hydrogen peroxide in mediating these effects.

Abscisic acid-induced hydrogen peroxide is required for anthocyanin accumulation in leaves of rice seedlings

The role of hydrogen peroxide (H(2)O(2)) in abscisic acid (ABA)-induced anthocyanin accumulation in detached and intact leaves of rice seedlings was investigated. Treatment with ABA resulted in an accumulation of anthocyanins in detached rice leaves. Dimethylthiourea, a chemical trap for H(2)O(2), was observed to be effective in inhibiting ABA-induced accumulation of anthocyanins. Inhibitors of NADPH oxidase (diphenyleneiodonium chloride and imidazole), phosphatidylinositol 3-kinase (wortmannin and LY 294002), and a donor of nitric oxide (N-tert-butyl-alpha-phenylnitrone), which have previously been shown to prevent ABA-induced H(2)O(2) accumulation in detached rice leaves, inhibited ABA-induced anthocyanin increase. Exogenous application of H(2)O(2), however, was found to increase the anthocyanin content of detached rice leaves. In terms of H(2)O(2) accumulation, intact (attached) leaves of rice seedlings of cultivar Taichung Native 1 (TN1) are ABA sensitive and those of cultivar Tainung 67 (TNG67) are ABA insensitive. Upon treatment with ABA, H(2)O(2) and anthocyanins accumulated in leaves of TN1 seedlings but not in leaves of TNG67. Our results, obtained from detached and intact leaves of rice seedlings, suggest that H(2)O(2) is involved in ABA-induced anthocyanin accumulation in this species.

Nitrogen Dioxide-Induced Responses in Brassica campestris Seedlings: The Role of Hydrogen Peroxide in the Modulation of Antioxidative Level and Induced Resistance

This article investigates the responses of Brassica campestris seedlings to an acute level of nitrogen dioxide (NO 2) exposure in a plant growth chamber, and examines whether pretreating plants with hydrogen peroxide (H 2O 2) will alleviate NO 2-caused injury. Twenty-eight-day-old B. campestris plants sprayed with 10 mmol L −1 H 2O 2 aqueous solution (corresponding to approximate 1.0 mg H 2O 2 per single plant) were exposed to different concentrations of NO 2 (0.25, 0.5, 1.0, and 2.0 μL L −1, respectively) for 24 h under controlled environment. To measure the plant biomass, the plants were fumigated with the same NO 2 concentrations as mentioned above for 7 h per day (8.00-15.00) for 7 days. As a control, charcoal filtered air alone was applied. Data were collected on plant biomass, total chlorophyll, photosynthetic rate, stomatal conductance, nitrate and nitrate reductase (NR), antioxidative enzymes, ascorbate (ASA), and malondialdehyde (MDA), immediately after exposure. The results showed that exposure to a moderate dose of NO 2 (e.g., 0.25 μL L −1) had a favorable effect on plants, and the dry weight of the above-ground part increased, whereas the exposure to high NO 2 concentrations (e.g., 0.5 μL L −1 or higher) caused a reduction in the plant biomass and the total chlorophyll, when compared with the control. In addition, at 0.5 μL L −1 or higher NO 2 concentrations, prominent increases in the MDA level and superoxide dismutase (SOD) and NR activities were observed. Exposure to 1 μL L −1 and higher NO 2 resulted in necroses appearing on older leaves, and an increase in catalase (CAT) activity, decrease in ASA content, increased accumulation of NO 3, and reduction in photosynthesis, when compared with the controls. No changes were detected in stomatal conductance under NO 2 fumigation. The pretreatment with 10 mmol L −1 H 2O 2 alleviated significantly NO 2-caused biomass decrease and photosynthetic inhibition when compared with H 2O 2-untreated plants. Under NO 2 fumigation, further induction in SOD and CAT activities occurred in H 2O 2 treated plants when compared with H 2O 2-untreated plants. The effect of NO 2 on the ASA and MDA contents was also absent in H 2O 2-treated plants. However, the H 2O 2 treatment did not alter the nitrate content and NR activity in plants under NO 2 fumigation. The H 2O 2 treatment caused a lower rate of stomatal conductance. Taken together, these data suggest that fumigation with an acute level of NO 2 causes oxidative damage to B. campestris seedlings. The H 2O 2 pretreatment markedly protects plants against NO 2 stress and this may be associated with inducible antioxidative level. NO 2 fumigation contributes, at least in part, to the enhanced levels of nitrate in B. campestris leaves.

Roles of Hydrogen Peroxide in Thyroid Physiology and Disease

The long-lived thyroid cell generates, for the synthesis of thyroid hormones, important amounts of H2O2 that are toxic in other cell types. This review analyzes the protection mechanisms of the cell and the pathological consequences of disorders of this system. The literature on H2O2 generation and disposal, thyroid hormone synthesis, and their control in the human thyroid is analyzed. In humans, H2O2 production by dual-oxidases and consequently thyroid hormone synthesis by thyroperoxidase are controlled by the phospholipase C-Ca2+-diacylglycerol arm of TSH receptor action. H2O2 in various cell types, and presumably in thyroid cells, is a signal, a mitogen, a mutagen, a carcinogen, and a killer. The various protection mechanisms of the thyroid cell against H2O2 are analyzed. They include the separation of the generating enzymes (dual-oxidases), their coupling to thyroperoxidase in a proposed complex, the thyroxisome, and H2O2 degradation systems. It is proposed that various pathologies can be explained, at least in part, by overproduction and lack of degradation of H2O2 (tumorigenesis, myxedematous cretinism, and thyroiditis) and by failure of the H2O2 generation or its positive control system (congenital hypothyroidism).

Hydrogen Peroxide in the Troposphere

The past few decades saw a rising interest in the role of hydrogen peroxide (H2O2) in atmospheric chemistry and its contribution to the formation of free radicals. Free radicals (oxidants) are formed by photochemical reactions between ozone and H2O2. Free radicals formed within cells can oxidise biomolecules, and this may lead to cell death and tissue injury. For this reason, free radicals are believed to cause more than 100 diseases. H2O2 has been suggested as a better indicator of atmospheric oxidation capacity than ozone. Atmospheric H2O2 can appear in the gas phase or in the aqueous phase. It shows typical diurnal and seasonal variations. However, measurements of H2O2 with expensive and sophisticated equipment are rare and limited to but a few sites in the world. Measurements in Greenland ice cores showed that H2O2 concentrations increased over the last 200 years and most of the increase has occurred over the last 20 years. Evaluations show that concentrations will still rise as a result of decreasing SO2 emission. H2O2 measurements have not been carried out in Croatia until now, and, accompanied by the existing longterm measurements of ozone and nitrogen oxides, they will provide an idea of the oxidative capacity of the atmosphere and its influence on oxidative stress.

A role for hydrogen peroxide in inflammatory hyperalgesia of the mouse hindpaw

Reactive oxygen species, including hydrogen peroxide (H2O2), are released from activated leucocytes and resident cells in the joint during inflammation. We hypothesize that H2O2 is an important mediator of inflammatory pain and, thus, the aim of our experiments was to investigate the effect of H2O2 on inflammation of the mouse hindpaw. We performed behavioural studies in CD1 mice to determine the effect of H2O2 on both thermal and mechanical hyperalgesia and oedema formation 20 minutes after intraplantar injection into the mouse hindpaw. The Hargreaves technique was used to test thermal hyperalgesia and a dynamic plantar aesthesiometer was used for mechanical hyperalgesia studies. Oedema was determined by measuring paw mass. Our experiments showed intraplantar injection of H2O2 (2200–8800 nmoles) causes significant thermal and mechanical hyperalgesia of the mouse hindpaw. H2O2 also causes significant oedema formation. Thus, we propose that H2O2 is a potential target for the treatment of inflammatory pain.

Role of hydrogen peroxide during the interaction between the hemibiotrophic fungal pathogen Septoria tritici and wheat

Hydrogen peroxide (H(2)O(2)) is reported to inhibit biotrophic but benefit necrotrophic pathogens. Infection by necrotrophs can result in a massive accumulation of H(2)O(2) in hosts. Little is known of how pathogens with both growth types are affected (hemibiotrophs). The hemibiotroph, Septoria tritici, infecting wheat (Triticum aestivum) is inhibited by H(2)O(2) during the biotrophic phase, but a large H(2)O(2) accumulation occurs in the host during reproduction. Here, we infiltrated catalase, H(2)O(2) or water into wheat during the biotrophic or the necrotrophic phase of S. tritici and studied the effect of infection on host physiology to get an understanding of the survival strategy of the pathogen. H(2)O(2) removal by catalase at both early and late stages made plants more susceptible, whereas H(2)O(2) made them more resistant. H(2)O(2) is harmful to S. tritici throughout its life cycle, but it can be tolerated. The late accumulation of H(2)O(2) is unlikely to result from down-regulation of photosynthesis, but probably originates from damage to the peroxisomes during the general tissue collapse, which is accompanied by release of soluble sugars in a susceptible cultivar.

The role of hydrogen peroxide in regulation of plant metabolism and cellular signalling in response to environmental stresses.

Hydrogen peroxide (H2O2) is produced predominantly in plant cells during photosynthesis and photorespiration, and to a lesser extent, in respiration processes. It is the most stable of the so-called reactive oxygen species (ROS), and therefore plays a crucial role as a signalling molecule in various physiological processes. Intra- and intercellular levels of H2O2 increase during environmental stresses. Hydrogen peroxide interacts with thiol-containing proteins and activates different signalling pathways as well as transcription factors, which in turn regulate gene expression and cell-cycle processes. Genetic systems controlling cellular redox homeostasis and H2O2 signalling are discussed. In addition to photosynthetic and respiratory metabolism, the extracellular matrix (ECM) plays an important role in the generation of H2O2, which regulates plant growth, development, acclimatory and defence responses. During various environmental stresses the highest levels of H2O2 are observed in the leaf veins. Most of our knowledge about H2O2 in plants has been obtained from obligate C3 plants. The potential role of H2O2 in the photosynthetic mode of carbon assimilation, such as C4 metabolism and CAM (Crassulacean acid metabolism) is discussed. We speculate that early in the evolution of oxygenic photosynthesis on Earth, H2O2 could have been involved in the evolution of modern photosystem II.

Role of Hydrogen Peroxide in Mycoplasma pneumoniae-induced Mast Cell IL-4 Production

RATIONALE: We have previously described activation of mast cells for cytokine production by Mycoplasma pneumoniae, which is known to produce large amounts of H2O2 during normal metabolism. H2O2 is now recognized to function as a signaling molecule, augmenting tyrosine phosphorylation by oxidizing an essential cysteine within the active site of protein tyrosine phosphatases. We hypothesized that adherent M. pneumoniae activates mast cells through H2O2 produced at the mast cell membrane contact point.

Coumarin derivatives protection against ROS production in cellular models of Aβ toxicities

The role of oxidative stress and free radicals in the development of Alzheimer's disease (AD) has been the focus of many recent studies. The role of hydrogen peroxide (H2O2) in AD is thought to be associated with Aβ (amyloid – β) damage in cells. A number of coumarin derivatives were previously found to be potent anti-inflammatory and antioxidant agents. Herein, these coumarin derivatives were tested as H2O2 scavengers with the DCF assay using two types of neuronal cells: (a) wild type (N2a) neuroblastoma cells and (b) APP/PS1 transgenic cell line expressing Aβ. Their scavenging activity was varied between the types of cell cultures and it was found to be concentration and time dependent in the mutant cells. Their protective role against cell death further supports this notion. These results suggest that these compounds could be used as a template in the design of new molecules with a possible role in AD.

Role of hydrogen peroxide and apoplastic peroxidase in tomato — Botrytis cinerea interaction

The aim of the research was to estimate the sensitivity of tomato tissue and spore from necrotrophic isolate of B. cinerea on H2O2. The influence of exogenic H2O2 and B. cinerea on plant tissue and on the activity of peroxidases (PO), catalase (CAT) and superoxide dismutase (SOD) in apoplastic tomato leaves fraction were investigated.

Fragmentation of the gastrodermis and detachment of zooxanthellae in symbiotic cnidarians: a role for hydrogen peroxide and Ca2+ in coral bleaching and algal density control

Coral bleaching involves the detachment of zooxanthellae and the simultaneous fragmentation of the gastrodermis. Results obtained with a cell permeant fluorescent probe for calcium ions (Ca2+) indicates that “thermal” bleaching is the result of a temperature related breakdown of the Ca2+ exclusion system. “Solar” bleaching, which takes place at lower temperatures and is driven by light, is the result of a build-up of photosynthetically produced hydrogen peroxide in the tissues. Gastrodermal tissue with its symbionts, scraped from between septa of corals, was observed under controlled conditions of high light and temperature. Pieces of gastrodermis round off, zooxanthellae move to the surface, protrude from the surface and after a delay, detach, surrounded by a thin layer of host cytoplasm, inclusions and plasma membrane. The higher the temperature and light level the shorter the delay and higher the rate of algal detachment. Fragmentation by the ballooning-out and detachment of small spheres of cytoplasm (bleb formation) takes place simultaneously. This is likely to be due to oxidation, by hydrogen peroxide (H2O2), of -SH groups on the cytoskeleton and its attachment to the plasma membrane. Ground, polished and stained thin acrylic resin sections reveal similar processes taking place in artificially bleached corals. Isolated zooxanthellae and whole corals are shown to release H2O2 in the light. This process of algal detachment and fragmentation that takes place at normal sea temperatures may underlie the mechanism limiting algal populations in the gastrodermis and may be localized to areas with a concentration of algae near the membrane. At above-normal temperatures under the synergistic effect of light and temperature, the rate of production of H2O2 exceeds the rate at which can it be lost by diffusion or destroyed and H2O2 accumulates. This results in damage to the calcium exclusion system, detachment of zooxanthellae into the coelenteron and fragmentation of the gastrodermis. Rev. Biol. Trop. 54 (Suppl. 3): 79-96. Epub 2007 Jan. 15.

The involvement of hydrogen peroxide in UV-B-inhibited pollen germination and tube growth of Paeonia suffruticosa and Paulownia tomentosa in vitro

Previous studies have shown that UV-B could affect pollen germination and tube growth. However, the mechanism of response of pollen to UV-B has not been clear. The purpose of this study was to investigate the role of hydrogen peroxide (H2O2) in the UV-B-induced reduction of in vitro pollen germination and tube growth of Paeonia suffruticosa Andr. and Paulownia tomentosa Steud. Exposure of pollen of the two species to 0.4 and 0.8 W m−2 UV-B radiation for 3 h resulted in not only the reduction of pollen germination and tube growth, but also the H2O2 production in pollen grain and tube. Also, exogenous H2O2 inhibited pollen germination and tube growth of the two species in a dose-dependence manner. Two scavengers of H2O2, ascorbic acid and catalase, largely prevented not only the H2O2 generation, but also the reduction of pollen germination and tube growth induced by UV-B radiation in the two species. These results indicate that H2O2 is involved in the UV-B-inhibited pollen germination and tube growth.

Involvement of calcium-mediated apoptotic signals in H 2O 2-induced MIN6N8a cell death

Reactive oxygen species are believed to be the central mediators of beta-cell destruction that leads to type 1 and 2 diabetes, and calcium has been reported to be an important mediator of beta cell death. In the present study, the authors investigated whether Ca 2+ plays a role in hydrogen peroxide (H 2O 2)-induced MIN6N8a mouse beta cell death. Treatment with low concentration H 2O 2 (50 μM) was found to be sufficient to reduce MIN6N8a cell viability by 55%, largely via apoptosis. However, this H 2O 2-induced cell death was near completely blocked by pretreatment with BAPTA/AM (5 μM), a chelator of intracellular Ca 2+. Moreover, the intracellular calcium store channel blockers, such as, xestospongin c and ryanodine, significant protected cells from 50 μM H 2O 2-induced cell death and under extracellular Ca 2+-free conditions, 50 μM H 2O 2 elicited transient [Ca 2+] i increases. In addition, pharmacologic inhibitors of calpain, calcineurin, and calcium/calmodulin-dependent protein kinase II were found to have a protective effect on H 2O 2-induced death. Moreover, H 2O 2-induced apoptotic signals, such as c-JUN N-terminal kinase activation, cytochrome c release, caspase 3 activation, and poly (ADP-ribose) polymerase cleavage were all down-regulated by the intracellular Ca 2+ chelation. These findings show that [Ca 2+] i elevation, possibly due to release from intracellular calcium stores and the subsequent activation of Ca 2+-mediated apoptotic signals, critically mediates low concentration H 2O 2-induced MIN6N8a cell death. These findings suggest that a breakdown of calcium homeostasis by low level of reactive oxygen species may be involved in beta cell destruction during diabetes development.

Point:Counterpoint: Hypoxic pulmonary vasoconstriction is/is not mediated by increased production of reactive oxygen species

This series of debates was initiated for the Journal of Applied Physiology because we believe an important means of searching for truth is through debate where contradictory viewpoints are put forward. This dialectic process whereby a thesis is advanced, then opposed by an antithesis, with a

Reactive Oxygen Species Augment the Angiogenic Response in Rat Skeletal Muscle

Reactive oxygen species have previously been shown to play a role in angiogenesis. The goal of this study was to determine if blocking the action of the enzyme catalase to increase levels of hydrogen peroxide would increase the angiogenic response in exercising skeletal muscle. Seven week old male Sprague Dawley rats were implanted with an electrical stimulator on the peroneal nerve, and the tibialis anterior muscle was subjected to intermittent stimulation for 8 hours per day for 7 days to induce unilateral hind limb angiogenesis. Rats received either 1 ml of saline or 1 ml of 3-amino-1,2,4-triazole (3AT, 1mg/kg) daily for three days before surgery, and for the duration of the experiment. Control and 3AT animals both underwent significant angiogenesis in the stimulated leg as compared to the unstimulated leg (11.4% increase in control, 15.5% increase in 3AT). Additionally, administration of 3AT resulted in a significant increase in baseline vessel density as well as an augmentation of the angiogenic response to stimulation (17.9%). These data suggest a possible role for hydrogen peroxide in the angiogenic response and provide insight into the role of other reactive oxygen species and nitric oxide in angiogenesis in exercising skeletal muscle. Support, NIH HL 29587.