Effects of N-hexacosanol on nitric oxide synthase system in diabetic rat nephropathy.
We attempted to clarify the effects of cyclohexenonic long-chain fatty alcohol (N-hexacosanol) on nitric oxide synthase (NOS) in streptozotocin-induced diabetic nephropathy. After induction of experimental diabetes with streptozotocin, rats were maintained for 8 weeks with or without treatment by N-hexacosanol (8 mg/kg i.p. every day). Urinary albumin excretion, blood chemistry, immunoblot analysis, and real-time polymerase chain reactions (real-time PCR) of endothelial nitric oxide synthase (eNOS), inducible NOS (iNOS), and neuronal NOS (nNOS) were investigated. Although N-hexacosanol had no effects on serum glucose or insulin level, it normalized serum creatinine and urinary albumin excretion. N-hexacosanol was found to improve the diabetes-induced alterations in the eNOS, iNOS, and nNOS protein and their mRNA levels. Histologically, N-hexacosanol inhibited the progression to glomerular sclerosis. Our data suggest that N-hexacosanol improves diabetes-induced NOS alterations in the kidney, resulting in the amelioration of diabetic nephropathy.
Division of Pediatrics and Perinatology, Tottori University, 36-1 Nishi-machi, Yonago, Tottori, Japan.
Shinichi
S
Okada
Motoaki
M
Saito
Emi
E
Kazuyama
Takuya
T
Hanada
Yasuo
Y
Kawaba
Atsushi
A
Hayashi
Keisuke
K
Satoh
Susumu
S
Kanzaki
D000818:Animals; D003928:Diabetic Nephropathies / Q000201:enzymology* / Q000473:pathology; D005233:Fatty Alcohols / Q000494:pharmacology*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D015151:Immunoblotting; D007668:Kidney / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D008297:Male; D009566:Nitrates / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000378:metabolism*; D052248:Nitric Oxide Synthase Type I / Q000235:genetics / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000235:genetics / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D005233:Fatty Alcohols; D009566:Nitrates; D009573:Nitrites; D012333:RNA, Messenger; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C051942:1-hexacosanol