Dietary nitrite inhibits early glomerular injury in streptozotocin-induced diabetic nephropathy in rats.
Increased production of reactive oxygen species (ROS) is a key event leading to microvascular complications, including nephropathy, in diabetes mellitus (DM). Excessive ROS and oxidative stress in DM have been reported to be associated with subsequent impaired nitric oxide (NO) bioavailability. The aim of this study is to examine the beneficial function of dietary nitrite supplementation as an interventional NO donor to attenuate early progression of diabetic nephropathy. To test this hypothesis, male Sprague-Dawley rats were randomly divided into four groups: non-diabetic rats given water with or without nitrite (nitrite-treated or untreated, respectively), and streptozotocin-induced diabetic rats given water with or without nitrite (nitrite-treated or untreated, respectively). After a 4 week experimental period, untreated diabetic rats exhibited significantly higher malondialdehyde (MDA) levels in the kidney compared with untreated non-diabetic rats, accompanied by a reduction in levels of endogenous NO synthase-derived nitrite. However, dietary nitrite supplementation to diabetic rats not only decreased MDA levels but also increased nitrite levels in the kidney to the same levels as in the non-diabetic kidney. These improvements accompanied an improvement in the parameters of glomerular injury, including urinary protein and albumin excretion, histopathological glomerular hypertrophy, and mesangial matrix accumulation. These results indicate that dietary nitrite is effective in the prevention of early diabetic glomerular injury in which NO bioavailability is impaired.
Ohtake
Kazuo
K
Division of Pathophysiology, Department of Clinical Dietetics and Human Nutrition, Faculty of Pharmaceutical Science, Josai University, Saitama, Japan.
Ishiyama
Yuichi
Y
Uchida
Hiroyuki
H
Muraki
Etsuko
E
Kobayashi
Jun
J
D000818:Animals; D003928:Diabetic Nephropathies / Q000139:chemically induced / Q000150:complications* / Q000188:drug therapy; D019587:Dietary Supplements; D007668:Kidney / Q000737:chemistry; D007674:Kidney Diseases / Q000209:etiology / Q000517:prevention & control*; D008297:Male; D008315:Malondialdehyde / Q000032:analysis; D009573:Nitrites / Q000008:administration & dosage / Q000032:analysis / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species
D009573:Nitrites; D017382:Reactive Oxygen Species; D008315:Malondialdehyde