title: Antioxidant diet and sex interact to regulate NOS isoform expression and glomerular mesangium proliferation in Zucker diabetic rat kidney.
abstract: Oxidative stress contributes substantially to the pathophysiology of diabetic nephropathy (DN). Consumption of an antioxidant-fortified (AO) diet from an early age prevents or delays later development of DN in the Zucker rat female with type 2 diabetes. We hypothesize this is due to effects on mesangial matrix and renal nitric oxide synthase (NOS) distribution and to sex-specific differences in NOS responses in the diabetic kidney. Total glomerular tuft area (GTA) and PAS-positive tuft area (PTA), endothelial (e), neuronal (n) and inducible (i) NOS were quantified in males and females on AO or regular (REG) diet at 6 and 20 weeks of age. eNOS was observed in glomeruli and tubules. nNOS predominantly localized to tubular epithelium in both cortex and medulla. iNOS was expressed in proximal and distal tubules and collecting ducts. Sex, diabetes duration and AO diet affected the distribution of the three isoforms. GTA and PTA increased with duration of hyperglycemia and showed a negative correlation with renal levels of all NOS isoforms. AO diet in both genders was associated with less PAS-positive staining and less mesangial expansion than the REG diet, an early increase in cortical iNOS in males, and sex-specific changes in cortical eNOS at 20 weeks. These effects of AO diet may contribute to sex-specific preservation of renal function in females.
authors.affiliation: Department of Biomedical Sciences, Ohio University, Athens, OH 45701, USA; The Diabetes Institute at Ohio University, Ohio University, Athens, OH 45701, USA.
authors.forename: Yuriy
authors.initials: Y
authors.lastname: Slyvka
authors.affiliation: Department of Biomedical Sciences, Ohio University, Athens, OH 45701, USA; Program in Molecular and Cellular Biology, Ohio University, Athens, OH 45701, USA; The Diabetes Institute at Ohio University, Ohio University, Athens, OH 45701, USA.
authors.forename: Ramiro
authors.initials: R
authors.lastname: Malgor
authors.affiliation: Department of Biomedical Sciences, Ohio University, Athens, OH 45701, USA; Program in Molecular and Cellular Biology, Ohio University, Athens, OH 45701, USA; The Diabetes Institute at Ohio University, Ohio University, Athens, OH 45701, USA.
authors.forename: Sharon R
authors.initials: SR
authors.lastname: Inman
authors.affiliation: College of Natural Sciences, School of Biological Sciences, University of Texas at Austin, TX 78713, USA.
authors.forename: Julia
authors.initials: J
authors.lastname: Ding
authors.affiliation: OUHCOM Office of Research & Grants, Ohio University, Athens, OH 45701, USA.
authors.forename: Victor
authors.initials: V
authors.lastname: Heh
authors.affiliation: Department of Biomedical Sciences, Ohio University, Athens, OH 45701, USA; Program in Molecular and Cellular Biology, Ohio University, Athens, OH 45701, USA; The Diabetes Institute at Ohio University, Ohio University, Athens, OH 45701, USA. Electronic address: nowak@ohio.edu.
authors.forename: Felicia V
authors.initials: FV
authors.lastname: Nowak
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000178:diet therapy / Q000201:enzymology*; D003928:Diabetic Nephropathies / Q000178:diet therapy / Q000201:enzymology* / Q000209:etiology; D004032:Diet; D005260:Female; D007527:Isoenzymes / Q000378:metabolism; D007678:Kidney Glomerulus / Q000201:enzymology / Q000473:pathology; D008297:Male; D050527:Mesangial Cells / Q000201:enzymology*; D052248:Nitric Oxide Synthase Type I / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism*; D011924:Rats, Zucker; D012727:Sex Characteristics
chemical_list: D000975:Antioxidants; D007527:Isoenzymes; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496318:Nos2 protein, rat; C496316:Nos3 protein, rat
keywords: Antioxidant diet; Diabetic nephropathy; Mesangial matrix; Nitric oxide synthases; Obesity; Sex difference