Selective inhibition of cyclooxygenase (COX) derived oxylipins reduces disease progression in the Han:SPRD-Cy rat model of cystic kidney disease, but the roles of lipoxygenase (LOX) and cytochrome P450 (CYP) derived products in this disease are not known. Dietary soy protein (SP), fish oil (FO) and flax oil (FXO) are beneficial in retarding renal disease progression in this and other models of cystic kidney disease and can alter renal oxylipin production through different mechanisms. The general objectives of this thesis were to: 1) investigate the effects of disease on renal oxylipin levels (produced from the three enzymatic pathways); 2) investigate the synergistic and additive effects of combining dietary SP with FO or FXO on disease progression, renal fatty acid composition, and renal oxylipin levels; 3) compare the effects of COX and LOX inhibitors on oxylipin levels and disease progression, in the Han:SPRD-Cy rat model of cystic kidney disease. Our research demonstrates that COX oxylipins are elevated and n-6 derived LOX metabolites are reduced in diseased kidneys in this model of cystic kidney disease. N-3 polyunsaturated fatty acid (PUFA) derived LOX oxylipins, including those derived from alpha-linolenic acid (ALA) and docosahexaenoic acid (DHA) were also lower in diseased kidneys, as were CYP derived oxylipins. The beneficial effect of SP on disease was associated with amelioration of several oxylipin alterations in parallel with a reduction in kidney disease progression, improvement in kidney function and blood pressure. However, adding dietary FO or FXO to the SP diet improved some but worsened other oxylipin alterations and did not provide further disease protection. Since both COX1 and COX2 activities are elevated in diseased kidneys, the effect of aspirin was examined; this treatment slowed disease progression and the decline in kidney function. On the other hand, inhibiting the LOX pathway had no effects on disease. Thus interventions that specifically inhibit COX while maintaining LOX and CYP may be more effective than general oxylipin inhibitors in slowing disease in this renal disorder. / October 2015

Gentamicin-induced nephrotoxicity varies temporally, with a peak being observed when this antibiotic is administered during the resting period and a trough when given during the activity period of rats. These variations are modified by fasting and by restricted feeding schedules. In this study, food and water intakes of adult female Sprague-Dawley rats were measured during pre-treatment (days 1 to 5) and during treatment (days 6 to 10) with gentamicin (80 mg/kg/day, i.p.) injected at 1300 h or 0100 h. A significantly higher level of serum creatinine was observed when gentamicin was administered at 1300 h compared to 0100 h, and a significantly lower creatinine clearance was found in rats treated with gentamicin at 1300 h compared to those treated with saline at the same time. Gentamicin treatment at 1300 h or 0100 h resulted in a decrease in the 24 h food intake. In addition, in the gentamicin-treated group at 0100 h, the maximal food intake observed at late dark during the pre-treatment period decreased during treatment, and early dark rather than late dark maximal intake occurred. Our data demonstrate that gentamicin induces a nephrotoxicity that varies temporally, and that gentamicin treatment inhibits food intake and alters its nocturnal variations.

<p>Research suggests that parents&rsquo / feeding practices play a critical role in the development of children&rsquo / s tastes, eating habits, nutrition and eventual weight status. Thus if parental feeding practices play such a critical role, the question arises as to whether there is a difference in parental feeding practices that determine different developments in children&rsquo / s nutritional habits. Furthermore, feeding practices are possibly based on the nutritional knowledge of parents. The aim of this study was to assess the Body Mass Index (BMI), nutritional knowledge and behaviour of primary care-givers. This study followed the quantitative research paradigm. A sample of 147 staff members, who were primary care- givers of children at a University in the Western Cape was self-selected to participate in the study. Only primary care-givers of children were invited to participate. The primary care-givers were asked to complete two online questionnaires, the Comprehensive Child Feeding Questionnaire (CFPQ) developed by Musher-E-Eisenman and Holub (2007), and the General Nutritional Knowledge Questionnaire (GNKQ) for adults. Data analysis was done by means of the Statistical Package for Social Sciences (SPSS17). Results indicated that the majority of participants were overweight (46% of the participants). Primary care-givers across all body mass index groups did not lack nutritional knowledge but variations in behaviour were found with regard to feeding practices. However similarities were found in the BMI categories in the areas of teaching about nutrition, pressure to eat at meal times<br /> and encouraging balance and variety.</p>

Caffeine has been implicated in a number of health conditions, but the mechanisms and physiological pathways affected are not all well understood. Genetic variation in the caffeine metabolizing gene, CYP1A2 (rs762551), is associated with differences in caffeine metabolism and disease risk. The objectives of this thesis were to determine the association between caffeine intake and the plasma proteome and whether CYP1A2 genotype modifies any associations. Subjects (n=1095) were from the Toronto Nutrigenomics and Healthy Study. Initially, no significant associations were seen between caffeine intake and 54 high-abundance plasma proteins. After stratification by CYP1A2 genotype, plasma gelsolin levels decreased significantly with increasing caffeine intake among the slow metabolizers (A/C +C/C). These results suggest that plasma gelsolin levels are affected by caffeine intake and this association is only evident among slow metabolizers. Gelsolin may have a role in mediating some of the biological effects of caffeine.

Caffeine has been implicated in a number of health conditions, but the mechanisms and physiological pathways affected are not all well understood. Genetic variation in the caffeine metabolizing gene, CYP1A2 (rs762551), is associated with differences in caffeine metabolism and disease risk. The objectives of this thesis were to determine the association between caffeine intake and the plasma proteome and whether CYP1A2 genotype modifies any associations. Subjects (n=1095) were from the Toronto Nutrigenomics and Healthy Study. Initially, no significant associations were seen between caffeine intake and 54 high-abundance plasma proteins. After stratification by CYP1A2 genotype, plasma gelsolin levels decreased significantly with increasing caffeine intake among the slow metabolizers (A/C +C/C). These results suggest that plasma gelsolin levels are affected by caffeine intake and this association is only evident among slow metabolizers. Gelsolin may have a role in mediating some of the biological effects of caffeine.

Macronutrient composition of food was shown to have a potent impact in modulating circadian rhythms of gentamicin toxicity. In the present study, adult female Sprague-Dawley rats fully adapted to isocaloric 20 casein-containing, 20% soy-containing (both semi-purified with 10% safflower oil and 58.55% carbohydrate) or a standard chow diet (non-purified with 18.1% mixed proteins, 4.5% fat and 57.3% carbohydrate) were chronically treated for 10 days with a nephrotoxic dose of gentamicin sulfate (40 mg/kg/day, i.p.) or a saline solution given in the middle of their resting period or in the middle of their activity period. Body weights, 24-h, 12-h light and 12-h dark food intakes were measured before (Days 1 to 5) and during treatment (Days 6 to 15). Gentamicin nephrotoxicity indices including serum creatinine, creatinine clearance, urinary proteins, urinary enzymes activities, corticocefular regeneration and cortical accumulation of gentamicin were measured at specific time points during the experiment. (Abstract shortened by UMI.)

All aminoglycosides have the potential to cause nephrotoxicity. Previous studies have shown that this toxicity was altered according to the macronutrient composition of dietary regimens offered to female rats. In a first study, adult female Sprague-Dawley rats adapted to a standard chow diet, the standard chow with 20% added casein or with 55% added casein were treated for 10 days with a nephrotoxic dose of gentamicin sulfate (40 mg/kg/day, i.p.) or a saline solution. Food ingestion patterns and gentamicin nephrotoxicity indices were measured. In a second study, rats were fed the same diets, however, the treatment given was a sham injection. Results suggest that chronic gentamicin treatment leads to a decrease in food intake and flattening of the rhythms of food ingestion. Also, chow feeding and chow added with 20% casein were found to be more protective against gentamicin-induced nephrotoxicity than chow added with 55% casein.

Graduation date: 1979

Thesis (M.S)--Oklahoma State University, 2007. / Vita. Includes bibliographical references.

Thesis (M.S.)--Oklahoma State University, 2007. / Vita. Includes bibliographical references.