Renal cyclooxygenase and lipoxygenase products are altered in polycystic kidneys and by dietary soy protein and fish oil treatment in the Han: SPRD-Cy rat

Scope: Dietary fish oil (FO) and soy protein (SP) are two interventions that slow disease progression in the Han:SPRD-Cy rat model of polycystic kidney disease (PKD). Inhibition of cyclooxygenase (COX)-derived eicosanoids also reduces disease progression, but the role of lipoxygenase (LOX) products in this disease is not known. Methods and results: Since dietary FO and SP have been shown to alter eicosanoid formation via differing mechanisms, Han:SPRD-Cy rats were given diets containing either casein protein (CP) or SP, and soy oil (SO) or FO. Analysis of eicosanoids revealed that renal COX products were higher and LOX products were lower in diseased kidneys. SP feeding resulted in lower COX products, activity and COX1 protein and higher LOX products in the diseased kidneys in parallel with reduced renal cyst growth and fibrosis. By comparison, FO reduced both COX and LOX products produced from n-6 fatty acids and increased 3-series prostanoids in both normal and diseased cortex and medulla, but these differences did not parallel effects on disease. Conclusion: Renal COX-derived eicosanoids are elevated and LOX products are reduced in this model of kidney disease. The effects of dietary SP, but not FO, on renal eicosanoids parallel the effects on disease.