Oxysterols increase in diabetic rats.
To address whether diabetes enhances lipid peroxidation and attenuates nitric oxide (NO) generation resulting in tissue complications, we measured oxysterols and NO metabolites (NOx) in the tissues of diabetic Wistar rats. After 4 weeks of streptozotocin injection (STZ, 80 mg/kg, i.p.), we measured 7 alpha- and 7 beta-hydroperoxycholest-5-en-3 beta-ol (7 alpha-OOH and 7 beta-OOH), 7 alpha- and 7 beta-hydroxycholesterol (7 alpha-OH and 7 beta-OH) and 7-ketocholesterol (7-keto) by HPLC in the kidneys, heart, and liver. All the oxysterols were much higher in the diabetic than in sham rats, while the extent of the increase was higher in the order of the kidney, heart, and liver. Together with high blood urea nitrogen, the data indicate that the kidney is the predominant target of early diabetic complications. Plasma NOx were decreased by 20% in the STZ rats. The enhanced oxidative stress in diabetes would increase oxysterols by peroxidation, while superoxide is known to reduce NO by reaction to form another potent oxidant peroxynitrite.
Yoshioka
Naoki
N
Department of Legal Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan.
Adachi
Junko
J
Ueno
Yasuhiro
Y
Yoshida
Ken-Ichi
K
D000818:Animals; D001806:Blood Urea Nitrogen; D002784:Cholesterol / Q000031:analogs & derivatives* / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D048909:Diabetes Complications; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism* / Q000473:pathology; D006321:Heart / Q000502:physiology; D007668:Kidney / Q000378:metabolism; D015227:Lipid Peroxidation; D008099:Liver / Q000378:metabolism; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D018384:Oxidative Stress; D030421:Peroxynitrous Acid / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013311:Streptozocin / Q000633:toxicity; D013481:Superoxides / Q000378:metabolism
D013481:Superoxides; D030421:Peroxynitrous Acid; D009569:Nitric Oxide; D013311:Streptozocin; D002784:Cholesterol