title: Cyclooxygenase product inhibition with acetylsalicylic acid slows disease progression in the Han:SPRD-Cy rat model of polycystic kidney disease.
abstract: Renal cyclooxygenase (COX) derived eicosanoids are elevated and lipoxygenase (LOX) products are reduced in the Han:SPRD-Cy rat model of polycystic kidney disease (PKD). Selective COX2 inhibition reduces kidney disease progression, but COX1 levels also are elevated in this model. Since the effect of reducing the products of both COX isoforms and the role of LOX products is not known, weanling normal and diseased Han:SPRD-cy littermates were given either low dose acetylsalicylic acid (ASA), nordihydroguaiaretic (NDGA) or no treatment for eight weeks. Renal eicosanoids were altered in the diseased compared to normal cortex, with COX products being higher and LOX products being lower. ASA reduced COX products, cyst growth and kidney water content, while NDGA reduced LOX products without altering disease progression or kidney function. Hence, a human equivalent ASA dose equal to less than one regular strength aspirin per day slowed disease progression, while further reduction of LOX products did not worsen disease progression.
authors.affiliation: Department of Human Nutritional Sciences, University of Manitoba, Winnipeg, Manitoba, Canada; Canadian Centre for Agri-Food Research in Health and Medicine, St. Boniface Hospital Research Centre, Winnipeg, Manitoba, Canada; the Richardson Center for Functional Foods and Nutraceuticals, Canada.
authors.forename: Naser H M
authors.initials: NH
authors.lastname: Ibrahim
authors.affiliation: Department of Human Nutritional Sciences, University of Manitoba, Winnipeg, Manitoba, Canada; Canadian Centre for Agri-Food Research in Health and Medicine, St. Boniface Hospital Research Centre, Winnipeg, Manitoba, Canada.
authors.forename: Melanie
authors.initials: M
authors.lastname: Gregoire
authors.affiliation: Department of Human Nutritional Sciences, University of Manitoba, Winnipeg, Manitoba, Canada; Canadian Centre for Agri-Food Research in Health and Medicine, St. Boniface Hospital Research Centre, Winnipeg, Manitoba, Canada.
authors.forename: Jessay G
authors.initials: JG
authors.lastname: Devassy
authors.affiliation: Department of Human Nutritional Sciences, University of Manitoba, Winnipeg, Manitoba, Canada; Canadian Centre for Agri-Food Research in Health and Medicine, St. Boniface Hospital Research Centre, Winnipeg, Manitoba, Canada.
authors.forename: Yinhong
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Education and Research Center of Animal Models for Human Diseases, Fujita Health University, Toyoake, Aichi, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Yoshihara
authors.affiliation: Department of Human Nutritional Sciences, University of Manitoba, Winnipeg, Manitoba, Canada; Canadian Centre for Agri-Food Research in Health and Medicine, St. Boniface Hospital Research Centre, Winnipeg, Manitoba, Canada.
authors.forename: Tamio
authors.initials: T
authors.lastname: Yamaguchi
authors.affiliation: Education and Research Center of Animal Models for Human Diseases, Fujita Health University, Toyoake, Aichi, Japan.
authors.forename: Shizuko
authors.initials: S
authors.lastname: Nagao
authors.affiliation: Department of Human Nutritional Sciences, University of Manitoba, Winnipeg, Manitoba, Canada; Canadian Centre for Agri-Food Research in Health and Medicine, St. Boniface Hospital Research Centre, Winnipeg, Manitoba, Canada; Manitoba Institute of Child Health, Manitoba, Winnipeg, Manitoba, Canada; the Richardson Center for Functional Foods and Nutraceuticals, Canada. Electronic address: Aukema@UManitoba.ca.
authors.forename: Harold M
authors.initials: HM
authors.lastname: Aukema
mesh_terms: D000818:Animals; D001241:Aspirin / Q000494:pharmacology*; D051545:Cyclooxygenase 1 / Q000494:pharmacology*; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology*; D004195:Disease Models, Animal; D006801:Humans; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D008084:Lipoxygenase / Q000378:metabolism*; D008297:Male; D009637:Masoprocol / Q000494:pharmacology*; D008565:Membrane Proteins / Q000494:pharmacology*; D007690:Polycystic Kidney Diseases / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D051381:Rats
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D008565:Membrane Proteins; D009637:Masoprocol; D008084:Lipoxygenase; D051545:Cyclooxygenase 1; C496513:Ptgs1 protein, rat; D001241:Aspirin
keywords: Acetylsalicylic acid; Eicosanoid; NDGA; Polycystic kidney disease