No description available.

No description available.

The acute cellular responses to DNA damaging agents are critical in determining the long term outcome of disease. A cell’s susceptibility to damage, or its capacity to remove or repair this damage, all contributes to the eventual health or disease of tissues. This process is especially crucial in colonic epithelial cells and in the development of colorectal oncogenesis. The colonic lumen is constantly subjected to different environmental compounds that may have genotoxic properties that can initiate mutational events and possibly carcinogenesis. Therefore, the study of a regulatory dietary agent that improves the colonic cells ability to withstand damage, improve repair and retain its general health is a significant and practical tool in the fight against colorectal cancer. The health benefits of fish oil, including its potential chemopreventative properties, have been reported in numerous studies. However, the mechanism by which this protective effect occurs remains unclear. A gap in current literature exists that fails to explore the effect of fish oil on the early cellular responses to carcinogenic agents. Therefore, this thesis aims to firstly, better understand the specific host responses to an insult of carcinogen in vivo; secondly, to determine if regulation of these responses can be achieved by dietary fish oil; and lastly, to explore the potential consequences of this regulation for colorectal oncogenesis. All experimental work was carried out using a rat – azoxymethane (AOM) animal model of colorectal carcinogenesis. The key host responses to the carcinogen that were measured included the formation of acute O6methyldeoxyGuanosine (O6medG) DNA damage, the acute apoptotic response to genotoxic carcinogen (AARGC) and cell proliferation rates. A novel immunochemical assay was designed to detect both the levels and distribution of O6medG in colonic cells. With this established, a pattern of these host responses were mapped out over time. A dietary intervention study trialling a range of fish oil diets containing different doses and forms was then carried out to determine if modulation of responses occurred. This study was then followed on by a longer term study that explored the consequences of regulation by fish oil on pre-neoplastic lesions in the colon. The acute host responses to an insult of AOM showed that colonic O6medG formation began 2h post AOM administration and peaked at 6h. The AARGC response followed the pattern of O6medG by a 2h delay, peaking at 8h post AOM administration, while cell proliferation rates decreased significantly after 6h. The inclusion of tuna oil in the diet did not affect either the AARGC or cell proliferation rates when given in any form or at any dose. Animals fed a diet with 15% free tuna oil and 7% encapsulated tuna oil did however have significantly reduced levels of O6medG DNA damage in the distal colon. This reduction in O6medG levels did not translate into a reduction of ACF lesion, with a protective effect against ACF lesions only being observed in animals fed the high dose fish oil groups. Analysis of the data suggest that the acute host responses to an insult of DNA damaging agent appear to be closely related, all reaching their peak level of response 6-8h after the insult. The short time frame between both O6medG and apoptosis also did not support the current popular theory which explains O6medG mediated apoptosis. An alternate hypothesised BER mediated apoptotic pathway was also not supported. Regulation of the acute apoptotic response or the cell proliferation rate was not achieved by dietary fish oil. However, a high dose fish oil diet did regulate the level of O6medG in colonic epithelial cells by significantly reducing the total O6medG DNA damage load. This reduction of O6medG by a high fish oil diet however, was not translated into a protective effect against the formation of pre-neoplastic lesions. These data suggests that regulation of the acute O6medG response to a damaging agent does not necessarily imply protection for longer term colorectal oncogenesis. Additional studies exploring both the effect of fish oil on AOM metabolising enzymes and also a longer term cancer study may help to answer some pertinent questions evolving from this thesis.

abstract: Background: Research in animal models suggests that fish oil ingestion may impair immunity and increase risk for infection. To date there are no studies examining this relationship between fish oil ingestion and risk for infection in humans. Objective: The primary aim of this randomized, placebo-controlled, double-blind, parallel-arm study was to examine the effect of 400 mg of EPA and 200 mg of DHA, the main components of fish oil (FO) supplements, on the incidence of symptoms related to upper respiratory tract infections in healthy young females, at a large southwestern university. Design: Healthy young women between 18 and 38 years of age who were non-obese (mean BMI 23.7 ± 0.6 kg/m2) were recruited from an urban southwestern university campus. Subjects were non-vegetarians, non-smokers, and reported consuming less than one serving (3.5 oz) of fish per week. Participants (n=26) were randomized according to age, body weight, BMI, and daily n-3 fatty acid (FA) intake into two groups: FO (one gel capsule of 600 mg EPA/DHA per day) or CO (one placebo gel capsule of 1000 mg coconut oil per day). Participants completed a validated daily cold symptom survey, the Wisconsin Upper Respiratory Symptom Survey-21 for 8 weeks. Fasting blood samples measuring TNF-α concentrations were taken at weeks 1 and 8, when 24-hour dietary recalls were also performed. Anthropometric measurements were recorded via bioelectrical impedance at trial weeks 1, 4, and 8. Results: The 8-week trial of FO supplementation did not significantly change the average score for perception of cold symptoms between FO and CO groups (167 ± 71 and 185 ± 56, p=0.418, respectively). Plasma TNF-α levels (pg/mL) did not differ between groups (p=0.482). TNF-α levels were significantly correlated with body weight (r=0.480, p=0.037), BMI (r=0.481, p=0.037, and percent body fat (r=0.511, p=0.025) at baseline. Conclusions: Healthy young women taking a fish oil supplement of 400 mg EPA and 200 mg DHA per day over 8 weeks does not impose unintentional health consequences. These findings do not refute the American Heart Association's current recommendations for all Americans to consume two servings (3.5 oz) of a variety of oily fish per week. Depending on the type of fish, this current recommendation equates to approximately 200-300 mg per day of EPA and DHA n-3 polyunsaturated fatty acids. Additional research is needed to investigate the effects of higher dosages of fish oils on daily cold symptoms. / Dissertation/Thesis / M.S. Nutrition 2013

Renal hypertrophy occurs early in the natural history of human and experimental diabetes and may be a manifestation of the same pathophysiological process which ultimately results in diabetic nephropathy. The precise biological events which stimulate and regulate this growth process remain incompletely understood. We postulated that renal eicosanoids contribute to the development of renal hypertrophy in diabetes. We elected to test the effects of suppression of dienoic eicosanoid metabolism (arachidonic acid metabolism) on renal hypertrophy in diabetic rats by feeding fish oil. Diabetic rats fed fish oil had markedly reduced insulin requirements compared to control rats pair-fed a beef tallow-rich diet. The concentrations of prostaglandin E2, 6-keto-prostaglandin F1α, and thromboxane B2 were depressed in the renal cortex of diabetic rats fed fish oil. This alteration in eicosanoid metabolism was associated with a substantial enhancement of diabetic renal hypertrophy. These results indicate that dietary fish oil has profound effects on renal eicosanoid metabolism in experimental diabetes and that these autocoids may participate in the biological events which regulate diabetic renal hypertrophy.

No description available.

Obesity is the most prevalent nutritional disorder encountered in small animal medicine. Problems related with obesity are the higher incidence of morbidity and mortality. Nutritional and physical activity interventions have been common strategies employed; however, they have shown low compliance rates. Because of it more attention has been given to the nutrient composition of diets. Using the canine model, three experiments were conducted to examine the effect of fish oil or barley on protein and lipid metabolism, as well as postprandial glycemia, and nutrient digestibility in mature and in young adult dogs. In Exp. 1, seven female dogs were randomly assigned to one of two isonitrogenous and isocaloric diets, control (CO) or fish oil (FO), in a crossover design. Animals fed the FO diet tended to be more sensitive to glucose, showing a lower glucose half life. Cholesterol and HDL decreased (p<0.05) on the FO treatment. Overall, the supplementation of fish oil may improve glucose clearance rate and is effective in decreasing cholesterol in mature overweight dogs. In Exp. 2, eight female Beagles were randomly assigned to one of two isonitrogenous and isocaloric diets, control (CO) or fish oil (FO), in a crossover design. Overall, feeding a FO containing diet showed a protective effect against the rise of plasma CHOL and it increased plasma ghrelin levels. However, it did not appear to improve protein metabolism or postprandial glycemia in adult lean dogs. In Exp. 3, sixteen female dogs were randomly assigned to four experimental diets; control (40% corn) or three levels of barley (10, 20, 40%). The data suggest that inclusion of barley up to 40% in diets for adult dogs is well tolerated and does not negatively impact nutrient digestibility of the diets. However, inclusion of barley did not improve aspects related to fecal odor, postprandial glycemia, or plasma cholesterol. Overall, the research presented herein suggests that different nutritional strategies - dietary lipid or carbohydrate manipulation - may be beneficial in ameliorating health issues (e.g., hyperlipidemia) or in improving the health status of dogs (e.g., gut health by increased SCFA production).

Master of Science / Department of Kinesiology / Timothy I. Musch / Impaired vasomotor control in chronic heart failure (CHF) limits the delivery of O[subscript]2 to skeletal muscle during exercise. Previous results demonstrate significant increases in skeletal muscle blood flow (BF) during exercise with omega-3 polyunsaturated fatty acid (PUFA) supplementation via fish oil (FO) versus safflower oil (SO) in healthy rats (Stebbins CL et al., Int J Sport Nutr Exerc Metab 20:475-86, 2010). Whether PUFA supplementation with FO will improve vasomotor control in CHF and skeletal muscle BF during exercise remains to be determined. This investigation tested the hypothesis that PUFA supplementation with FO would augment the skeletal muscle BF response to exercise in rats with CHF when compared to SO. CHF was induced in male Sprague-Dawley rats by myocardial infarction produced via left coronary artery ligation. Rats were then randomized to dietary FO (20% docosahexaenoic acid and 30% eicosapentaenoic acid, n = 8) or SO (5% safflower, n = 6) supplementation for 6 weeks. Rats remained on their respective diets until final experiments were conducted. Following acute instrumentation and recovery (> 1 hour), mean arterial pressure (MAP), skeletal muscle BF to the total hindlimb and individual muscles (via radiolabeled microspheres), and blood lactate concentration were determined during rest, submaximal treadmill exercise and exercise+LNAME (20 m · min[superscript]-[superscript]1, 5% incline). Left ventricular end-diastolic pressure (LVEDP) measured in the SO and FO groups during instrumentation were similar and demonstrated moderate CHF (LVEDP; SO: 14 ± 2; FO: 11 ± 1 mmHg, P>0.05). During submaximal exercise, MAP (SO: 128 ± 3; FO: 132 ± 3 mmHg) and blood lactate (SO: 3.8 ± 0.4; FO: 4.6 ± 0.5 mmol · l[superscript]-[superscript]1) were similar (P>0.05) between groups. Exercising hindlimb skeletal muscle BF was higher in SO compared to FO (SO: 120 ± 11; FO: 93 ± 4 ml · min[superscript]-[superscript]1 · 100 g[superscript]-[superscript]1). Specifically, 17 of 28 individual hindlimb muscle BF’s were higher (P<0.05) in SO. These data suggest that PUFA supplementation with FO in rats with moderate CHF decreases the skeletal muscle BF response to submaximal whole body exercise.

Thesis (MTech (Business Administration))--Peninsula Technikon, 2002. / Word processed copy. Summary in English. Includes bibliographical references (leaves 80-82). Also available online.

Although quality of commercial fish oil is of the upmost importance to both suppliers and consumers, it can be difficult to maintain due to rapid lipid oxidation attributable to the high levels of EPA and DHA. Fish oil quality can be assessed in a number of ways; this paper focuses on ethyl ester (EE) content and oxidation products. Fish oil supplements are sold as both triacylglycerols (TAG) and EE. TAG products are more resistant to oxidation, have better bioavailability and are generally considered to be of higher quality. Here, a method is described to quantify EE in fish oil using solid phase microextraction (SPME) headspace analysis and gas chromatography-mass spectrometry (GCMS). A related aspect of quality is state of oxidation and although the causes of oxidation in fish oil are well known, there is little research on the kinetics of the oxidation process. The work presented here monitors hydroperoxides to model the kinetics of oxidation in two commercially available fish oil supplements by fitting the data to the Arrhenius model. It was determined that the same mechanisms of oxidation hold at temperatures ? 40 °C and thus, this temperature was used in the final stages of this work where accelerated stability testing of fish oil was conducted. Currently, taste panels are the only reliable method to assess the sensory properties of fish oil, but these are costly and subjective. Described here is an alternative method using SPME-GCMS to monitor volatile oxidation products. Two different statistical methods were used to identify oxidative volatiles that correlate with sensory characteristics of fish oil. First, stepwise discriminant function analysis (DFA) was used to identify volatiles that could be used to classify oil as acceptable or unacceptable based on sensory analysis. Principal component analysis (PCA) and linear regression were then applied with greater success. Both techniques identified similar oxidative volatiles as being important to sensory properties. It is anticipated that these methods could be adopted by fish oil manufacturers as measures of quality.