In Parkinson's disease, severe damage to nigrostriatal neurons causes a depletion of the neurotransmitter dopamine (DA). Oxidative stress on the brain is thought to contribute to neuron cell death and to the onset of Parkinson's disease. Reactive oxygen radicals produced during oxidative stress have been implicated as an initiator of neuron destruction. Glutamate, an excitatory neurotransmitter, can initiate OH radical formation when present in excess. Oxidative stress on the brain caused by glutamate overflow may be monitored by trapping the OH radicals with salicylic acid to produce 2,3-dihydroxybenzoic acid (2,3-DHBA). Determination of this product is initially performed using capillary zone electrophoresis (CZE) coupled with UV detection to establish optimum separation conditions. These conditions were applied for rapid, efficient, and sensitive determination of 2,3-DHBA by CZE coupled with electrochemical detection. Quick and sensitive detection of 2,3-DHBA is essential in monitoring OH radical generation and identifying its role in Parkinson's disease. / Master of Science

Schizophrenia affects 1-1.5% of people in the United States alone. Haloperidol (HP), a butyrophenone and a typical antipsychotic, has been used as an antipsychotic drug in human. Unfortunately, the therapeutic effects of HP also come with severe extrapyramidal side effects, resulting in movement disorders in patients. Olanzapine, a new atypical neuroleptic, seems to have better efficacy, with less severe adverse effects. There has been increasing evidence of the role of reactive oxygen species (ROS) and oxidative stress in the pathogenesis of Schizophrenia. We therefore hypothesized that the differences between HP and Olz could be partly because of the differences in the oxidative stress they cause. We studied the pro-oxidant and antioxidant effects of these two drugs in vitro and examined the mechanism of their cytotoxicity in a neuronal cell model using PC-12 cells. HP was found to be ineffective as a superoxide radical scavenger but appeared to be a potent scavenger of hydroxyl radicals with a rate constant of ~6.78 X 109 M-1s-1. Olz on the other hand was found to scavenge hydroxyl radical at a rate of 34.1 X 109 M-1s-1. This was shown using the hydroxyl radical dependent deoxyribose degradation assay and EPR spin trapping methods. HP was also found to quench singlet oxygen in a dose-dependent manner. HP was found to enhance the microsomal lipid peroxidation in a dose-dependent manner and at 10 µM it augmented the lipid peroxide accumulation by 100% whereas Olz, at the same concentrations had trivial effects. Light microscopy and two cytometric apoptotic/viability probes (7-aminoactinomycin D and Annexin-V) were employed to evaluate mechanisms of drug-induced cell death in PC-12 pheochromocytoma cells exposed to HP or Olz. At low dose (50 µM), HP was more cytotoxic than Olz. At high concentrations (150 mM) each of these antipsychotic drugs caused a significant increase in cell death that was readily detectable by all the techniques. Light microscopy with trypan blue staining indicated that necrosis was the predominate form of cell death with both drugs. Apoptotic cells were rarely observed by microscopy in vehicle or drug-exposed cells. Further, no increase in early cellular apoptosis was observed using the Annexin-V probe. 7AAD and Annexin-V both showed drug-related increases in the late apoptotic/necrotic cell death window. These data, along with the cytologic evaluations suggest that cell death in PC-12 pheochromocytoma cells exposed to HP or Olz may primarily be necrotic in nature, rather than apoptotic. Because Olz at a low dose was less cytotoxic and was found to have lower pro-oxidant action than HP the secondary effects manifested in patients with chronic treatment with HP may, at least in part, be attributed to the pro-oxidant effects of the drug. / Master of Science

No / Vitiligo occurs in Northern Europe in one of 200 people. The disease can cause significant psychological stress for the affected individual. These patients generate and accumulate massive amounts of H2O2- and peroxynitrite in the epidermal compartment. Consequently many proteins are oxidized or nitrated, leading in turn to partial or complete loss of functionality. Moreover, presence of DNA damage in the skin as well as in plasma has been shown, while apoptosis is not enhanced. Induction of DNA repair is associated with up-regulated functioning p53 protein. Considering possible genetic predisposition and /or spontaneous mutations, autoimmune reactions in the disease are put forward in the context of oxidative stress. In addition a review of recent and novel treatment modalities including the role of oxidative stress reduction and combined climatotherapy at the Dead Sea in a group are discussed.

The decline of honey bee (Apis mellifera) colony numbers in recent years presents an economic and ecological threat to agriculture. One outstanding threat to honey bees is the unintended exposure to agricultural pesticides. Previous studies report that acute exposures to the common-use herbicide atrazine elicit oxidative stress in non-target insects; however, little information is currently available on the exposure risk of atrazine to honey bees. This project examined biochemical and molecular oxidative stress response markers of honey bees following laboratory and field treatments of atrazine. Laboratory experiments were conducted with honey bees exposed to increasing concentrations of atrazine for 24 h whereas hive experiments were conducted with bees exposed to one sub-lethal concentration of atrazine for 28 d. The overall antioxidant enzyme activities of atrazine-treated honey bees were decreased compared to the untreated honey bees in both the laboratory and hive experiments. After exposure to atrazine in the laboratory and field, semi-quantitative RT-PCR analysis of antioxidant-encoding genes reveals the differential expression of genes in atrazine-treated bees that are important for oxidative stress tolerance in the laboratory and field experiments. Here, we provide evidence that the laboratory and hive exposure of honey bees to the common-use herbicide atrazine results in oxidative stress responses that can compromise the health of bee colonies. The data will be discussed with regard to the protection of these pollinators against the untended exposure of agricultural pesticides. / Master of Science in Life Sciences / The pollination service provided by insects, primarily honey bees, is estimated to contribute approximately one-third of the diet consumed by the average American. Honey bees are vitally important pollinators due to their broad range of foraging activities and ease of husbandry within a managed colony. In recent decades, colony numbers have decreased in the developed areas of the planet and pesticide usage has been implicated in these losses. Atrazine is the second most commonly used agricultural herbicide in the country and has been linked to oxidative stress in beneficial insects in the past. Oxidative stress is the result of an uncontrolled build-up of reactive oxygen species in an aerobic organism. These reactive oxygen species are dangerous because they are capable of damaging proteins, DNA, and cell walls. Every aerobic organism also possesses antioxidant function which serves to prevent or counteract damage caused by reactive oxygen species. This study examined antioxidant enzyme activities and antioxidant-encoding gene expression levels, which were used as indicators of oxidative stress biomarkers, in honey bees exposed to atrazine in the laboratory and in the hive environment. Honey bees were exposed to atrazine at increasing concentrations in the laboratory for 24 h and at one environmentally relevant dose for 28 d in the hive. After exposure to atrazine in the laboratory and the hive, four out of five antioxidant enzyme levels of honey bees decreased which implied an increase in oxidative stress and a decrease in antioxidant defenses. Activity of one enzyme, lipid peroxidase, increased in honey bees after exposure to atrazine. Lipid peroxidase is the most common measure of cellular injury during oxidative stress, once again signifying an increase in reactive oxygen species production and oxidative stress. Expression levels of seven antioxidantencoding genes were examined in honey bees after atrazine exposure and expression levels of some genes changed compared to the untreated control and expression levels in some genes remained the same compared to the untreated control. These changes in antioxidant-encoding gene expression levels may imply an increase in oxidative stress due to exposure of the honey bees to atrazine. This study aimed to examine biomarkers of oxidative stress in honey bees exposed to the commonly used herbicide atrazine with the hope of raising awareness of harmful effects caused by atrazine and protecting these important pollinators from unintended exposure to agricultural pesticides.

Oxidant stress and injury is inherent in many human diseases such as ischemic vascular and respiratory diseases, heart failure, myocardial infarction, stroke, perinatal and placental insufficiencies, diabetes, cancer, and numerous psychiatric and neurodegenerative disorders. Finding novel therapeutics to combat the deleterious effects of oxidative stress is critical to create better therapeutic strategies for many conditions that have few treatment options. This study used the anoxia-tolerant fruit fly, Drosophila melanogaster, to investigate endogenous cellular protection mechanisms and potential interactions to determine their ability to regulate synaptic functional tolerance and cell survival during acute oxidative stress. The Drosophila larval neuromuscular junction (NMJ) was used to analyze synaptic transmission and specific motor axon contributions. Drosophila Schneider 2 (S2) cells were used to assess viability. Acute oxidative stress was induced using p harmacological paradigms that generate physiologically relevant oxidant species: mitochondrial superoxide production induced by sodium azide (NaN3) and hydroxyl radical formation via hydrogen peroxide (H2O2). A combination of genetic and pharmacological approaches were used to explore the hypothesis that endogenous protection mechanisms control cellular responses to stress by manipulating ion channel conductance and neurotransmission. Furthermore, this study analyzed a group of marine natural products, pseudopterosins, to identify compounds capable of modulating synaptic transmission during acute oxidative stress and potential novel neuromodulatory agents. / Includes bibliography. / Dissertation (Ph.D.)--Florida Atlantic University, 2015. / FAU Electronic Theses and Dissertations Collection

Zhang, Yang. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2013. / Includes bibliographical references (leaves 147-169). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese.

Lifestyle diseases such as cardiovascular diseases, hypertension, cancer, type 2 diabetes are the major causes of mortality and morbidity worldwide. The prevalence of these diseases is high in New Zealand as well. It is believed that promoting a healthy diet and increased physical activity can make beneficial changes and extend the healthy life expectancy. This twelve week study with follow-up at 52 weeks was designed to demonstrate if a diet and physical activity group intervention in the workplace would result in changes in risk factors for antioxidant damage and therefore reduce the risk for lifestyle diseases. The effect of the addition of kiwifruit to the diet on markers of oxidative stress was also measured in a crossover sub study within this study. Fifty two healthy subjects (male 24, female 28, mean age 46), completed the 12 week study with measurements points being at 0, 3, 6, 9 and 12 weeks. Thirty eight subjects presented for another set of measurements at 52 weeks. The intervention started at week 3 and the kiwifruit crossover treatment was launched between weeks 6 and 12.Ferric reducing ability of plasma (FRAP) assay was utilized to measure the changes in plasma antioxidant activity(AOA) and thiobarbituric acid reactive substances (TBARS) assay to measure the changes in plasma malondialdehyde (MDA), as a marker of lipid peroxidation (LP) at each measurement point. Since almost all participants had a normal range of baseline measurements of plasma AOA and LP (plasma MDA), they were categorized as relatively low and high AOA (1200micromol/L cut off point) and LP groups (1.70mmol/L cut off point), as well as divided into male and female groups. The effect of changed diet and increased physical activity during the 12 week study period resulted in a significant increase (P<0.05) in plasma AOA. The changes were much higher in low AOA group (P=0.005) and in male subjects (P<0.005), while no changes were observed in subjects with already high AOA at baseline. The increased plasma AOA level was maintained and increased even more over the year. No changes were observed in LP (plasma MDA). The effect of kiwifruit on the markers of oxidative stress was modest, the 3-week daily kiwifruit consumption (2-3 kiwifruit per day) resulted in significant increase (P=0.01) in plasma AOA only in female subjects within the low AOA group. However, the precision and validity of the measurements were limited by a possible loss of vitamin C due to storage of the plasma samples rather than analysis when fresh. Given that kiwifruit is particularly high in vitamin C the effect of the addition of kiwifruit to the diet might not have been detected. In this study it was shown that a group diet and physical activity intervention within the workplace can increase the level of plasma antioxidant activity and thereby reduce the risk for oxidative stress and related lifestyle diseases.

Thesis (Ph. D.)--West Virginia University, 2004. / Title from document title page. Document formatted into pages; contains ix, 148 p. : ill. (some col.). Includes abstract. Includes bibliographical references (p. 132-148).

Lifestyle diseases such as cardiovascular diseases, hypertension, cancer, type 2 diabetes are the major causes of mortality and morbidity worldwide. The prevalence of these diseases is high in New Zealand as well. It is believed that promoting a healthy diet and increased physical activity can make beneficial changes and extend the healthy life expectancy. This twelve week study with follow-up at 52 weeks was designed to demonstrate if a diet and physical activity group intervention in the workplace would result in changes in risk factors for antioxidant damage and therefore reduce the risk for lifestyle diseases. The effect of the addition of kiwifruit to the diet on markers of oxidative stress was also measured in a crossover sub study within this study. Fifty two healthy subjects (male 24, female 28, mean age 46), completed the 12 week study with measurements points being at 0, 3, 6, 9 and 12 weeks. Thirty eight subjects presented for another set of measurements at 52 weeks. The intervention started at week 3 and the kiwifruit crossover treatment was launched between weeks 6 and 12.Ferric reducing ability of plasma (FRAP) assay was utilized to measure the changes in plasma antioxidant activity(AOA) and thiobarbituric acid reactive substances (TBARS) assay to measure the changes in plasma malondialdehyde (MDA), as a marker of lipid peroxidation (LP) at each measurement point. Since almost all participants had a normal range of baseline measurements of plasma AOA and LP (plasma MDA), they were categorized as relatively low and high AOA (1200micromol/L cut off point) and LP groups (1.70mmol/L cut off point), as well as divided into male and female groups. The effect of changed diet and increased physical activity during the 12 week study period resulted in a significant increase (P<0.05) in plasma AOA. The changes were much higher in low AOA group (P=0.005) and in male subjects (P<0.005), while no changes were observed in subjects with already high AOA at baseline. The increased plasma AOA level was maintained and increased even more over the year. No changes were observed in LP (plasma MDA). The effect of kiwifruit on the markers of oxidative stress was modest, the 3-week daily kiwifruit consumption (2-3 kiwifruit per day) resulted in significant increase (P=0.01) in plasma AOA only in female subjects within the low AOA group. However, the precision and validity of the measurements were limited by a possible loss of vitamin C due to storage of the plasma samples rather than analysis when fresh. Given that kiwifruit is particularly high in vitamin C the effect of the addition of kiwifruit to the diet might not have been detected. In this study it was shown that a group diet and physical activity intervention within the workplace can increase the level of plasma antioxidant activity and thereby reduce the risk for oxidative stress and related lifestyle diseases.

[Truncated abstract] Current understanding of atherosclerosis suggests that it is a chronic inflammatory disease, and that increased oxidative stress may be an important pathological event contributing to the disease process. There has been interest in the ability of dietary derived nutrients such as vitamin E, to act as antioxidants and protect against atherosclerosis. Despite promising epidemiological data which suggested benefits from a higher intake of &alpha-tocopherol (&alphaT), one of the major forms of dietary vitamin E, for protection against atherosclerosis, large scale, randomised controlled trials have generally shown no protective effect of high dose &alphaT supplementation. Recent studies suggest that the other major dietary tocopherol isomer, &gamma-tocopherol (&gammaT), may possess biological activities not shared by &alphaT. Supplementation with &gammaT, or mixtures of tocopherols rich in &gammaT, have shown biological activities that may help protect against atherosclerosis. The aim of this PhD project is to further characterise the biological relevance of ?T for protection against CVD... Both ?- and mixed tocopherol supplementation resulted in reduced plasma F2-isoprostanes (P < 0.001 and P = 0.001, respectively) but did not affect 24 hour urinary F2-isoprostanes and erythrocyte antioxidant enzyme activities. Neither &alphaT nor mixed tocopherol supplementation affected any measured plasma markers of inflammation. The tocopherol supplementation also did not affect COX-2 activity as assessed by 14 stimulated whole blood prostaglandin E2 synthesis, and urinary prostacyclin metabolite output. Compared to the placebo group, stimulated neutrophil leukotriene B4 (LTB4) production decreased significantly in the mixed tocopherol group (P=0.02) but not in the &alphaT group (P=0.15). The ability of both pure &alphaT and mixed tocopherol supplementation to reduce systemic lipid peroxidation in patients with type 2 diabetes, suggests potential benefits of vitamin E supplementation in this population. However, despite decreasing oxidative stress, our results also suggests that in populations with well controlled type 2 diabetes, supplementation with either &alphaT, or mixed tocopherol rich in &gammaT, is unlikely to confer further benefits in reducing systemic inflammation. Future research into the possible unique biological activity of different tocopherol isomers other than &alphaT, for example, their ability to affect the 5-LO pathway and production of inflammatory mediators such as LTB4, is warranted.