Reactive Species Generation Rate Research Articles

Unexpected effect of iodine atoms in heptamethine cyanine dyes on the photodynamic eradication of Gram-positive and Gram-negative pathogens

The introduction of heavy atoms such as iodine into organic dye molecules is known to improve the efficacy of photodynamic therapy (PDT) in general and antimicrobial photodynamic therapy (APDT) in particular. Such a phenomenon is attributed to the increasing probability of spin–orbit coupling resulting in the elevated rates of reactive species generation. In this work, we synthesize a series of novel, near-IR, iodinated heptamethine cyanine dyes containing carboxylic function and report on the unexpected effect of the increasing number of iodine atoms (up to six) on the photodynamic eradication of Gram-positive (Staphylococcus aureus) and Gram-negative (Escherichia coli and Pseudomonas aeruginosa) microbial pathogens. The efficacy of S. aureus photo-eradication by non-charged, zwitterionic cyanines increases with increasing the number of iodine atoms up to two, remains almost unchanged for the two-, three- and four-iodinated dyes, and reduces in the case of the hexa-iodinated cyanine. However, the mono-iodinated dye exhibits the most pronounced phototoxic effect to E. coli and P. aeruginosa. An additional positive charge provided by a triethylammonium group decreases photokilling of S. aureus but improves inactivation of E. coli and P. aeruginosa.

Possible role of seasonality and harmful algal blooms (HAB) on the oxidative and nitrosative metabolisms in hemocytes

Bivalves survive to biotoxin consumption but their metabolism could be affected. The objective of this work was to study the oxidative and nitrosative changes in the hemocytes of the mussel Mytilus edulis platensis in different seasons, including spring, characterized by the appearance of harmful algal blooms (HAB). Reactive species generation rate (measured as the 2′,7′dichlorofluorescein diacetate oxidation rate) was increased by 2.5- and 8.3-fold in hemocytes from spring and summer, respectively, as compared to winter samples. Neither total Fe nor labile Fe pool content was changed in the three seasons. Superoxide anion generation rate was 3-fold higher in spring as compared to winter and summer samples. Catalase content in spring cells were significantly higher as compared to winter (60%) and summer (3-fold increase) but glutathione-S-transferase activity only increased compared to summer season (125% increase). Lipid radical content in spring samples was 140 and 50% higher as compared to cells from winter and summer, respectively. Nitric oxide and nitro-tyrosine content were significantly higher in samples from spring as compared to values obtained either in winter or summer cells. Considering the aspects that influence metabolism, changes in temperature seem to mainly affect the oxidative over the nitrosative condition of the hemocytes. Nevertheless, HAB biotoxins seem as a contributing factor to affect not only reactive oxygen species generation, antioxidant activity and protein/lipid damage, but also the nitrosative metabolism. In this regard, the changes in the nitric oxide content are new and critical evidence that HAB-related toxins could affect reactive nitrogen species metabolism.

Potential biomarkers associated with oxidative stress for risk assessment of colorectal cancer.

Cells are continuously threatened by the damage caused by reactive oxygen/nitrogen species (ROS/RNS), which are produced during physiological oxygen metabolism. In our review, we will summarize the latest reports on the role of oxidative stress and oxidative stress-induced signaling pathways in the etiology of colorectal cancer. The differences in ROS generation may influence the levels of oxidized proteins, lipids, and DNA damage, thus contributing to the higher susceptibility of colon. Reactive species (RS) of various types are formed and are powerful oxidizing agents, capable of damaging DNA and other biomolecules. Increased formation of RS can promote the development of malignancy, and the "normal" rates of RS generation may account for the increased risk of cancer development in the aged. In this review, we focus on the role of oxidative stress in the etiology of colorec-tal cancer and discuss free radicals and free radical-stimulated pathways in colorectal carcinogenesis.

A new paradigm for XOR-catalyzed reactive species generation in the endothelium.

A plethora of vascular pathology is associated with inflammation, hypoxia and elevated rates of reactive species generation. A critical source of these reactive species is the purine catabolizing enzyme xanthine oxidoreductase (XOR) as numerous reports over the past 30 years have demonstrated XOR inhibition to be salutary. Despite this long standing association between increased vascular XOR activity and negative clinical outcomes, recent reports reveal a new paradigm whereby the enzymatic activity of XOR mediates beneficial outcomes by catalyzing the one electron reduction of nitrite (NO2(-)) to nitric oxide (NO) when NO2(-) and/or nitrate (NO3(-)) levels are enhanced either via dietary or pharmacologic means. These observations seemingly countervail numerous reports of improved outcomes in similar models upon XOR inhibition in the absence of NO2(-) treatment affirming the need for a more clear understanding of the mechanisms underpinning the product identity of XOR. To establish the micro-environmental conditions requisite for in vivo XOR-catalyzed oxidant and NO production, this review assesses the impact of pH, O2 tension, enzyme-endothelial interactions, substrate concentrations and catalytic differences between xanthine oxidase (XO) and xanthine dehydrogenase (XDH). As such, it reveals critical information necessary to distinguish if pursuit of NO2(-) supplementation will afford greater benefit than inhibition strategies and thus enhance the efficacy of current approaches to treat vascular pathology.

Dispelling dogma and misconceptions regarding the most pharmacologically targetable source of reactive species in inflammatory disease, xanthine oxidoreductase.

Xanthine oxidoreductase (XOR), the molybdoflavin enzyme responsible for the terminal steps of purine degradation in humans, is also recognized as a significant source of reactive species contributory to inflammatory disease. In animal models and clinical studies, inhibition of XOR has resulted in diminution of symptoms and enhancement of function in a number of pathologies including heart failure, diabetes, sickle cell anemia, hypertension and ischemia-reperfusion injury. For decades, XOR involvement in pathologic processes has been established by salutary outcomes attained from treatment with the XOR inhibitor allopurinol. This has served to frame a working dogma that elevation of XOR-specific activity is associated with enhanced rates of reactive species generation that mediate negative outcomes. While adherence to this narrowly focused practice of designating elevated XOR activity to be "bad" has produced some benefit, it has also led to significant underdevelopment of the processes mediating XOR regulation, identification of alternative reactants and products as well as micro-environmental factors that alter enzymatic activity. This is exemplified by recent reports: (1) identifying XOR as a nitrite reductase and thus a source of beneficial nitric oxide ((•)NO) under in vivo conditions similar to those where XOR inhibition has been assumed an optimal treatment choice, (2) describing XOR-derived uric acid (UA) as a critical pro-inflammatory mediator in vascular and metabolic disease and (3) ascribing an antioxidant/protective role for XOR-derived UA. When taken together, these proposed and countervailing functions of XOR affirm the need for a more comprehensive evaluation of product formation as well as the factors that govern product identity. As such, this review will critically evaluate XOR-catalyzed oxidant, (•)NO and UA formation as well as identify factors that mediate their production, inhibition and the resultant impact on inflammatory disease.