The vacuolar iron transporter mediates iron detoxification in Toxoplasma gondii

Iron is essential to living cells, acting as a cofactor in a number of important enzymes in metabolism; however in the absence of correct storage iron forms dangerous oxygen radicals. In both yeast and plants, iron is stored in a membrane-bound vacuole through the action of a vacuolar iron transporter (VIT). This transporter is conserved in the apicomplexan family of obligate intracellular parasites, including in Toxoplasma gondii, a pathogen of medical and veterinary importance. Here, we assess the role of VIT, and iron storage, in T. gondii. We show that iron is restricted to a compartment in the parasite that does not overlap with zinc. By deleting VIT we find a slight growth defect in vitro, however the absence of VIT leads to hypersensitivity to iron, confirming its essential role in iron detoxification in the parasite. This hypersensitivity can be rescued by scavenging of oxygen radicals. In the absence of VIT, parasites store less iron and are at a growth disadvantage when moving into an iron-depleted environment. We show parasite VIT expression is regulated by iron levels at both the transcript and protein level, and by altering the distribution of VIT within the cell. In the absence of VIT, we find that T. gondii responds by altering expression of genes with a role in iron metabolism and by increasing the activity of the antioxidant protein catalase. We also show that iron detoxification has an important role both in parasite survival within macrophages and in virulence in a mouse model. Together, by demonstrating a critical role for VIT during iron detoxification in T. gondii, we reveal the importance of iron storage in the parasite and provide the first insight into the machinery involved.

Markers of Neuroinflammation in the Serum of Prepubertal Children with Fetal Alcohol Spectrum Disorders

Background: Fetal Alcohol Spectrum Disorders (FASD) are the manifestation of the damage caused by alcohol consumption during pregnancy. Children with Fetal Alcohol Syndrome (FAS), the extreme FASD manifestation, show both facial dysmorphology and mental retardation. Alcohol consumed during gestational age prejudices brain development by reducing, among others, the synthesis and release of neurotrophic factors and neuroinflammatory markers. Alcohol drinking induces also oxidative stress. Hypothesis/Objective : The present study aims at investigating the potential association between neurotrophins, neuroinflammation and oxidative stress in 12 prepubertal male and female FASD children diagnosed as FAS or partial FAS (pFAS). Methods: Accordingly, we analyzed, in the serum, the level of BDNF and NGF and the oxidative stress, as free oxygen radicals test (FORT) and free oxygen radicals defense (FORD). Moreover, serum levels of inflammatory mediators (IL-1α, IL-2, IL-6, IL-10, IL-12, MCP-1, TGF-β and TNF-α) involved in neuroinflammatory and oxidative processes have been investigated. Results: We demonstrated in pre-pubertal FASD children low serum levels of NGF and BDNF, respect to healthy controls. These changes were associated with higher serum presence of TNF-α and IL-1α. Quite interestingly, an elevation in the FORD was also found despite normal FORT levels. Moreover, we found a potentiation of IL-1α, IL-2, IL-10 and IL-1α1 in the analyzed female compared to male children. Conclusion: The present investigation shows an imbalance in the peripheral neuroimmune pathways that could be used in children as early biomarkers of the deficits observed in FASD.

Role of Oxygen Radicals in Alzheimer’s Disease: Focus on Tau Protein

Oxygen free radical burst is a prominent early event in the pathogenesis of Alzheimer’s disease (AD). Posttranslational modifications of Tau protein, primarily hyper-phosphorylation and truncation, are indicated as critical mediators of AD pathology. This finding is confirmed by the high levels of oxidative stress markers and by the increased susceptibility to oxygen radicals found in cultured neurons and in brains from transgenic animal models expressing toxic Tau forms, in concomitance with a dramatic reduction in their viability/survival. Here, we collect the latest progress in research focused on the reciprocal and dynamic interplay between oxygen radicals and pathological Tau, discussing how these harmful species cooperate and/or synergize in the progression of AD. In this context, a better understanding of the role of oxidative stress in determining Tau pathology, and vice versa, primarily could be able to define novel biomarkers of early stages of human tauopathies, including AD, and then to develop therapeutic strategies aimed at attenuating, halting, or reversing disease progression.

Photodynamic therapy in tuberculous pleural empyema

as a lethal outcome predictor. To enhance treatment efficacy, TPE local sanitation method utilizing antimicrobial photodynamic therapy (PDT) has been developed. This technique is based on the generation of oxygen radicals by the interaction of photosensitizers and light quanta which inactivate Mycobacterium tuberculosis and pyogenic flora. To assess the sanitizing and antimicrobial efficacy of PDT, 96 procedures were performed in 16 patients (in 14 cases, TPE was complicated by bronchopleural fistula, in 10 cases it developed after surgical treatment of pulmonary tuberculosis). After intrapleural instillation of phthalocyanine aluminum 0.5 mg, all walls of the empyema cavity were irradiated by laser radiation with the wavelength of 662 nm and light density of 30-100 J/cm2. The response to PDT of tuberculous pleural empyema was reported in 93.75% of cases (n = 15), with complete response observed in 75% of cases (n = 12).

Role of Oxidative Stress in the Pathogenesis of Amyotrophic Lateral Sclerosis: Antioxidant Metalloenzymes and Therapeutic Strategies

Amyotrophic lateral sclerosis (ALS) affects motor neurons in the cerebral cortex, brainstem and spinal cord and leads to death due to respiratory failure within three to five years. Although the clinical symptoms of this disease were first described in 1869 and it is the most common motor neuron disease and the most common neurodegenerative disease in middle-aged individuals, the exact etiopathogenesis of ALS remains unclear and it remains incurable. However, free oxygen radicals (i.e., molecules containing one or more free electrons) are known to contribute to the pathogenesis of this disease as they very readily bind intracellular structures, leading to functional impairment. Antioxidant enzymes, which are often metalloenzymes, inactivate free oxygen radicals by converting them into a less harmful substance. One of the most important antioxidant enzymes is Cu2+Zn2+ superoxide dismutase (SOD1), which is mutated in 20% of cases of the familial form of ALS (fALS) and up to 7% of sporadic ALS (sALS) cases. In addition, the proper functioning of catalase and glutathione peroxidase (GPx) is essential for antioxidant protection. In this review article, we focus on the mechanisms through which these enzymes are involved in the antioxidant response to oxidative stress and thus the pathogenesis of ALS and their potential as therapeutic targets.

The influence of gamma radiation on organic compounds having carbon ring and its application in dosimetry

The formation of highly oxidizing radicals in multifunctional-solid compounds upon irradiation with gamma-ray had been investigated. Five organic compounds having a single carbon ring had been used in the present investigation; these materials are 1-chloro-4-nitrobenzene, 4′-aminoacetophenone, 3′-hydroxyacetophenone, n-anthranilic acid, and triphenylmethane. These material were irradiated using 60Co radiation with different doses between 20 and 100 kGy. Electron spin resonance spectroscopy spotted increases of the resonance absorption having landé factor around 2.0113 ± 0.003 upon irradiation with the increasing of dose. This resonance absorption was related to the formation of long-lived oxygen radicals that were attached to one of the radiation synthesized compounds. The method of infrared absorption spectroscopy emphasized the formation of cyclic and aliphatic hexane in addition to the active oxygen radicals. n-Anthranilic acid was found to be suitable for radiation the dosimetry with long-lasting radiation signature as electron spin and also to determine the exposure dose. The time-lapse infrared and electron spin resonance measurements had been used to tracked the formation of active species within the time-lapsed after the end of exposure; results showed that the dosimetric signature may be used as a tracker for the time when the exposure happens.

Hydrogen Gas: A Novel Type of Antioxidant in Modulating Sexual Organs Homeostasis

Sex is a science of cutting edge but bathed in mystery. Coitus or sexual intercourse, which is at the core of sexual activities, requires healthy and functioning vessels to supply the pelvic region, thus contributing to clitoris erection and vaginal lubrication in female and penile erection in male. It is well known that nitric oxide (NO) is the main gas mediator of penile and clitoris erection. In addition, the lightest and diffusible gas molecule hydrogen (H2) has been shown to improve erectile dysfunction (ED), testis injuries, sperm motility in male, preserve ovarian function, protect against uterine inflammation, preeclampsia, and breast cancer in female. Mechanistically, H2 has strong abilities to attenuate excessive oxidative stress by selectively reducing cytotoxic oxygen radicals, modulate immunity and inflammation, and inhibit injuries-induced cell death. Therefore, H2 is a novel bioactive gas molecule involved in modulating sexual organs homeostasis.