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Effects of nitrosonifedipine, a photodegradation product of nifedipine, on diabetic nephropathy in type II diabetic mice
Author(s) -
Sakurada Takumi,
Ishizawa Keisuke,
Fujii Shoko,
Izawa-Ishizawa Yuki,
Imanishi Masaki,
Nuno Asami,
Kihira Yoshitaka,
Ikeda Yasumasa,
Tomita Shuhei,
Tsuchiya Koichiro,
Tamaki Toshiaki
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.691.2
Subject(s) - endocrinology , oxidative stress , medicine , diabetic nephropathy , kidney , reactive oxygen species , diabetes mellitus , nephropathy , renal hypertrophy , chemistry , biochemistry
As the number of the patients with diabetic nephropathy (DN) has been increasing worldwide despite current treatment, more patients have received dialysis treatment. Oxidative stress and endothelial damage are involved in the development and progression of DN. Recently, we have demonstrated that Nitrosonifedipine (NO‐NIF), a photolytic compound of nifedipine, possesses radical scavenging activity and improves endothelial cell damage induced by tumor necrosis factor‐α (TNF‐α). Therefore, in this study, we investigated the effect of NO‐NIF on DN by using KKAy mice developing type II diabetes. In NO‐NIF treated KKAy mice, the urinary protein and albumin were significantly decreased compared with non‐treated KKAy mice. The pathological analysis showed expanded glomerular mesangium in KKAy mice, which was suppressed by NO‐NIF administration. NO‐NIF decreased urinary 8‐hydroxy‐20‐deoxyguanosine and reactive oxygen species detected by dihydroethidium staining in kidney. The mRNA expression of TNF‐α in kidney was also inhibited by NO‐NIF. However, NO‐NIF had no effect on body weight, kidney weight, adipocyte hypertrophy, blood glucose levels, insulin resistance, and systolic blood pressure. We conclude that NO‐NIF protects diabetic renal dysfunction via the attenuation of oxidative stress, and it might be a potential drug for the prevention of DN.