Scavenging effect of nicorandil on free radicals and lipid peroxide in streptozotocin-induced diabetic rats.
Free radicals and lipid peroxide (LPO), easily formed in the diabetic state, play an important role in the development of diabetic complications. Potentially, nicorandil may reduce the production of free radicals and LPO in various organs. In fact, increased LPO levels in the serum, kidney, and cardiac muscle of diabetic (DM) rats were reduced by nicorandil treatment (N treatment). Xanthine oxidase (XOD), which produces free radicals, was decreased in the liver and increased in the kidney of DM rats compared with control rats, and these changes were prevented by N treatment. The concentration of Cu, Zn-superoxide dismutase (SOD) decreased in the cardiac muscle and increased in the kidney of DM rats, and these changes returned to normal after N treatment. The decreased concentration of Mn-SOD in the liver, kidney, and cardiac muscle from DM rats was also reversed by N treatment. The changes in catalase and glutathione peroxidase (GSH-PX) activities in DM rats were not improved effectively by N treatment. Another K-adenosine triphosphate (K-ATP) channel opener, tilisolol hydrochloride, had an effect similar to that of nicorandil. The effects of nicorandil and tilisolol were studied only in DM rats. These data imply that N treatment, as an antioxidative therapy, may be beneficial in preventing diabetic complications due to lipoperoxidation and free radicals in DM rats.
Mano
T
T
Department of Internal Medicine and Pharmacy, Fujita Health University School of Medicine and Hygiene, Toyoake, Aichi, Japan.
Shinohara
R
R
Nagasaka
A
A
Nakagawa
H
H
Uchimura
K
K
Hayashi
R
R
Nakano
I
I
Tsugawa
T
T
Watanabe
F
F
Kobayashi
T
T
Fujiwara
K
K
Nakai
A
A
Itoh
M
M
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D016166:Free Radical Scavengers / Q000494:pharmacology*; D007546:Isoquinolines / Q000494:pharmacology; D007668:Kidney / Q000201:enzymology / Q000378:metabolism; D008054:Lipid Peroxides / Q000097:blood / Q000378:metabolism*; D008099:Liver / Q000201:enzymology / Q000378:metabolism; D008297:Male; D020108:Nicorandil / Q000494:pharmacology*; D009994:Osmolar Concentration; D010210:Papillary Muscles / Q000201:enzymology / Q000378:metabolism; D015221:Potassium Channels / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000378:metabolism; D014969:Xanthine Oxidase / Q000378:metabolism
D016166:Free Radical Scavengers; D007546:Isoquinolines; D008054:Lipid Peroxides; D015221:Potassium Channels; D017382:Reactive Oxygen Species; D020108:Nicorandil; D013482:Superoxide Dismutase; D014969:Xanthine Oxidase; C036593:tilisolol