Effects of Diet and Disease on Renal Oxylipins and Related Enzymes in the Han:SPRD-Cy rat Model of Cystic Kidney Disease

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dc.contributor.authorIbrahim, Naser
dc.contributor.examiningcommitteeSuh, Miyoung (Human Nutritional Sciences) House, James (Human Nutritional Sciences) Wigle, Jeffrey (Biochemistry and Medical Genetics) Duncan, Alison (University of Guelph, Human health and Nutritional Sciences)en_US
dc.contributor.supervisorAukema, Harold (Human Nutritional Sciences)en_US
dc.date.accessioned2015-09-09T13:11:06Z
dc.date.available2015-09-09T13:11:06Z
dc.date.issued2014-04en_US
dc.date.issued2015-01en_US
dc.degree.disciplineHuman Nutritional Sciencesen_US
dc.degree.levelDoctor of Philosophy (Ph.D.)en_US
dc.description.abstractSelective 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.en_US
dc.description.noteOctober 2015en_US
dc.identifier.citationMolecular Nutrition & Food Researchen_US
dc.identifier.citationProstaglandins and Other Lipid Mediatorsen_US
dc.identifier.urihttp://hdl.handle.net/1993/30734
dc.language.isoengen_US
dc.publisherJohn Wiley and Sonsen_US
dc.publisherElsevieren_US
dc.rightsopen accessen_US
dc.subjectHuman Nutritional Sciencesen_US
dc.titleEffects of Diet and Disease on Renal Oxylipins and Related Enzymes in the Han:SPRD-Cy rat Model of Cystic Kidney Diseaseen_US
dc.typedoctoral thesisen_US
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