Comparison of blood parameters associated with exercise and the total antioxidant power in sled dogs supplemented with blueberries

Thesis (M.S.) University of Alaska Fairbanks, 2003Oxidative damage from free radicals plays an important role in several diseases such as cancer, Alzheimer's disease, and heart disease. Research indicates that exercise may contribute to oxidative stress. Fruits, such as blueberries, are good antioxidants because they contain phenolics that preferentially react with free radicals. Maintaining antioxidant levels by supplementing the diet with blueberries may prevent exercise-induced oxidative damage. Additionally, oxidative damage from exercise can temporarily suppress the immune system. The goal of our study was to compare antioxidant levels in sled dogs supplemented with blueberries. Total antioxidant power (TAP), haptoglobin, isoprostane and other blood parameters were measured in plasma samples from racing sled dogs before exercise, post-exercise, 24 hours post-exercise, and 48 hours post-exercise. Though isoprostane levels did not change throughout the study, creatine kinase levels increased post-exercise for all exercise dogs regardless of blueberry supplementation. Conflicting data makes it unclear as to whether blueberry supplementation reduces muscle damage, adding confusion to the lack of sound antioxidant data available for dogs. Regardless, dogs fed blueberries had a significantly higher TAP than control post-exercise. This suggests that dogs fed blueberries while exercising as compared to dogs fed a control diet while exercising, may be better protected against oxidative damage

Sled Dogs As A Sentinel And Model For Nutritional And Physiological Adaptation In The Circumpolar North

Thesis (Ph.D.) University of Alaska Fairbanks, 2007Sled dogs were investigated as a sentinel in studying adaptation to the circumpolar north. Exploratory data were collected to study the characteristics of melatonin and thyroid hormone and revealed an impact of day length, exercise and thermoregulation on production. Before western diets, circumpolar people had a low incidence of obesity, diabetes, and cardiovascular disease. Contrary to the risks associated with a high fat, high protein diet, health benefits can be attributed to a diet rich in omega-3 fatty acids and antioxidants, offered from subsistence foods. While subsistence diets have been shown to provide substantial health benefits, there are also risks associated with them as a result of industrialization and the widespread distribution of chemicals in the environment. Native people and their sled dogs are exposed to a variety of contaminants that have accumulated in the fish and game that they consume. The sled dogs in these villages are maintained on indigenous food, primarily salmon, and therefore they can be used as models for researching the effects that a subsistence diet might have on immune parameters. Several biomarkers of immune function and inflammation were measured in village sled dogs along the Yukon River. A reference kennel, maintained on a nutritionally balanced commercial diet, was also measured in all projects for comparison. The health indicators such as antioxidant status were inversely correlated with mercury exposure

Boosted Anti-Inflammatory Profile of Alaskan Sled Dogs After Consumption of Acute Doses of Wild Alaskan Blueberries

Research Poste

A Nonpolar Blueberry Fraction Blunts NADPH Oxidase Activation in Neuronal Cells Exposed to Tumor Necrosis Factor-α

Inflammation and oxidative stress are key to the progressive neuronal degeneration common to chronic pathologies, traumatic injuries, and aging processes in the CNS. The proinflammatory cytokine tumor necrosis factor-alpha (TNF-α) orchestrates cellular stress by stimulating the production and release of neurotoxic mediators including reactive oxygen species (ROS). NADPH oxidases (NOX), ubiquitously expressed in all cells, have recently emerged as pivotal ROS sources in aging and disease. We demonstrated the presence of potent NOX inhibitors in wild Alaska bog blueberries partitioning discretely into a nonpolar fraction with minimal antioxidant capacity and largely devoid of polyphenols. Incubation of SH-SY5Y human neuroblastoma cells with nonpolar blueberry fractions obstructed the coalescing of lipid rafts into large domains disrupting NOX assembly therein and abolishing ROS production characteristic for TNF-α exposure. These findings illuminate nutrition-derived lipid raft modulation as a novel therapeutic approach to blunt inflammatory and oxidative stress in the aging or diseased CNS

25(OH)D levels in trained versus sedentary university students at 64° north

Purpose: 25-hydroxyvitamin D (25[OH]D) deficiency is associated with compromised bone mineralisation, fatigue, suppressed immune function and unsatisfactory skeletal muscle recovery. We investigated the risk of 25(OH)D insufficiency or deficiency in endurance athletes compared to sedentary non-athletes living at 64° north. Methods: University student-athletes (TS) and sedentary students (SS) volunteered to participate in this study. TS engaged in regular exercise while SS exercised no more than 20 minutes/week. Metabolic Equivalent of Task (MET) scores for participants were determined. Vitamin D intake was assessed using the National Cancer Institute’s 24-hour food recall (ASA24). Fasting plasma 25(OH)D levels were quantified via enzyme-linked immunosorbent assay. Results: TS reported higher activity levels than SS as assessed with MET-minutes/week and ranking of physical activity levels (p < 0.05). The reported mean daily intake of vitamin D was higher in TS compared to SS (p < 0.05) while 25(OH)D plasma levels were lower in TS than in SS (p < 0.05). In total, 43.8% of the TS were either insufficient (31.3%) or deficient (12.5%) in 25(OH)D, while none of the SS were insufficient and 13.3% were deficient. Conclusion: TS are at increased risk of 25(OH)D insufficiency or deficiency compared to their sedentary counterparts residing at the same latitude, despite higher vitamin D intake

Selected plasma fatty acid levels in subsistence fed sled dogs along the Yukon River: a pilot study for biomonitoring

The introduction of the ‘western diet' marked a decline in omega-3 fatty acids rich foods and a concurrent increase in saturated and omega-6 fatty acids that persists today. Historically, circumpolar people have had a low incidence of obesity, diabetes and cardiovascular disease and this has been largely attributed to polyphenolic compounds and omega-3 fatty acids offered from subsistence foods. In this report, we studied sled dogs as an Arctic sentinel species for monitoring the effect of a changing diet on lipid profiles along the Yukon River. Subsistence fed village sled dogs along the Yukon River, maintained largely on salmon were compared with a control kennel maintained on commercial food. Profiles showed higher levels for long chain omega-3 fatty acids in village subsistence fed dogs compared to control dogs and an opposite trend for omega-6 fatty acids, establishing baseline levels for follow up studies. A comparison with data for previously published mercury levels from the same cohort of dogs revealed a positive correlation with alpha-linolenic fatty acid and a negative correlation with linoleic fatty acid. Food and nutritional security is a concern in the Arctic as the impacts of climate change and transport of contaminants become obvious. This study supports not only the nutritional value of a subsistence diet but also the utility of sled dogs as a sentinel for human dietary chang

Effects of Methylmercury exposure in 3T3-L1 Adipocytes

Mercury-containing compounds are environmental pollutants that have become increasingly consequential in the Arctic regions of North America due to processes of climate change increasing their release and availability at northern latitudes. Currently, the form of mercury known to be most detrimental to human health is methylmercury, CH3Hg+, which is found in the environment and accumulates in the tissues of piscivores, including those consumed by Alaska Natives through subsistence gathering. Much is known about the neurotoxicity of methylmercury after exposure to high concentrations, but little is known about toxicity to other tissues and cell types, particularly for long-term exposure and the lower concentrations that would occur through fish consumption. Effects of methylmercury exposure on 3T3-L1 adipocytes in culture were assessed using assays for cytotoxicity and an ELISA assay for vascular endothelial growth factor (VEGF), a signaling molecule shown to be important for maintaining metabolic status in adipose tissue. Results showed that exposure to methylmercury leads to significant toxicity in adipocytes at exposures of 100 ng/mL during later stages of differentiation, but lower methylmercury concentrations produced little to no toxicity. Results also showed that VEGF secretion is elevated in adipocytes exposed to methylmercury after the process of differentiating into mature, fat-storing cells. These results provide a basis for further exploration into metabolic consequences of methylmercury exposure on specific cell types and cell models

Bias, complexity, and uncertainty in ecosystem risk assessment: pharmaceuticals, a new challenge in scale and perspective

Because thousands of pharmaceutical and industrial compounds are in use today and distributed into ecosystems via waste water, effective analysis of environmental risk needs to change as our understanding of the complexity of ecosystem services grows. Klaminder et al (2014 Environ. Res. Lett. http://dx.doi.org/10.1088/1748-9326/9/8/084003 9 http://dx.doi.org/10.1088/1748-9326/9/8/084003 ) now provide some important observations on a methodological bias in standardized ecotoxicological tests. First, the authors show that the formalized use of control species in risk assessment impacts how data is judged and valued. Reducing quantitative uncertainty may improve the rigor of toxicological assays, but may also increase the risk of missing likely ecosystem-scale impacts, essentially ‘throwing the baby out with the bathwater’. Second, we should recognize the importance of integrating nature, complexity, and dynamics across temporal and spatial scales in relation to the unintended consequences of pharmaceuticals and their partial degradation products in the environment. Since ecosystems and our broader life support system are composed of various stability states with dynamic cycles, feedback can destabilize a system as we know it. Complex systems have emergent properties with high degrees of uncertainty and ecosystem risk assessments must report not only toxicological risks but also ‘benefits’. In addition, risk assessment must expand its scale from the molecular and cellular to that of the ecosystem with real world conditions. The authors’ findings that exposure to Oxazepam led to increased survival and aggressiveness should inform changes in standardized testing methodology as well as improvements in regulatory policy

Involvement of Cytokine IL-1Ra in Regulating the Secretion of VEGF in SH-SY5Y Neuroblastoma

Inflammation, neurodevelopment, and cancer areassociated with cellular features of signal transduction usingmolecules originally identified with functions that are part of theextended immune system. The expression of interleukin-1 (IL-1)and interleukin-1 receptor antagonist (IL-1Ra) is currently notwell understood in human neuronal cell types. The developmentof neutraceuticals from natural products as inexpensivepreventative therapies to protect against neurodevelopmentdisorders, neurodegeneration and cancer is a current focus ofbiotechnology research. To further study the role of cytokines inearly stage neuroinflammation, neurodegeneration and braincancer, SH-SY5Y neuroblastoma cells were characterized for thepresence of the IL-1 and IL1Ra, as well as vascular endothelialgrowth factor (VEGF). The expression of these cytokines wasmeasured using sensitive ELISA assays before and after stressingthe cells with TNF-. Using partially purified extract fractions ofthe wild Alaskan Bog Blueberries (BBX) on these cytokines andVEGF, the cells were pretreated with different BBX extract priorto TNF- exposure, and cytokine measurement. Intracellular IL-1Ra levels increased (13.6 g/mL) after exposure to TNF- whencompared to non-treated cells (6.7 g/mL). VEGF levels in theculture supernatant also increased compared to the control, 217.3g/mL versus 172.2 g/mL, respectively. BBX 8 increasedintracellular IL-1Ra protein levels (25.2 g/mL), while returningVEGF levels to normal. We hypothesize that compounds inblueberries enhance the signal transduction feedback leading to arestoration of the intracellular balance between IL-1 and IL-1Rasignals

A nonpolar blueberry fraction blunts NADPH oxidase activation in neuronal cells exposed to tumor necrosis factor alpha. Oxid Med Cell Longev. 2012: 1–12. doi: 10.1155/2012/768101 (open access article

Inflammation and oxidative stress are key to the progressive neuronal degeneration common to chronic pathologies, traumatic injuries, and aging processes in the CNS. The proinflammatory cytokine tumor necrosis factor-alpha (TNF-α) orchestrates cellular stress by stimulating the production and release of neurotoxic mediators including reactive oxygen species (ROS). NADPH oxidases (NOX), ubiquitously expressed in all cells, have recently emerged as pivotal ROS sources in aging and disease. We demonstrated the presence of potent NOX inhibitors in wild Alaska bog blueberries partitioning discretely into a nonpolar fraction with minimal antioxidant capacity and largely devoid of polyphenols. Incubation of SH-SY5Y human neuroblastoma cells with nonpolar blueberry fractions obstructed the coalescing of lipid rafts into large domains disrupting NOX assembly therein and abolishing ROS production characteristic for TNF-α exposure. These findings illuminate nutrition-derived lipid raft modulation as a novel therapeutic approach to blunt inflammatory and oxidative stress in the aging or diseased CNS