[Role of free radicals and reactive nitrogen species in the late complications of diabetes mellitus in rats].
In this time-course study the levels of different reactive species, especially those of nitric oxide and peroxynitrite were determined in streptozotocin-induced diabetic rat tissues at different time-points after the onset of the disease, before the development of histopathological damages. Significantly higher steady state free radical concentrations were found in the liver 3 weeks after the onset of diabetes, compared to age matched control groups. Increased nitric oxide levels in diabetic vasculature and kidney, and its rapid reaction with reactive oxygen species, resulted in high peroxynitrite generation. This suggested the onset of processes characteristic to premature aging of the endothelium. According to the histopathological results, there were no signs of late complications in the tissues up to seven weeks after induction of diabetes. In conclusion, the authors' experimental evidences support the idea of a complex role for nitric oxide, reactive oxygen species and peroxynitrite in the development of early diabetic tissue injury before the evolution of late complications. This study showed for the first time a time-course dependence for changes in nitric oxide production in diabetic tissues compared to age-matched controls at an early stage of the disease. These results suggest that oxidative stress in increased at a very early stage of diabetes and, in particular, that high levels of nitric oxide and peroxynitrite could play a decisive role in the development of late complications in the diabetic vasculature and kidney.
Stadler
Krisztián
K
Magyar Tudományos Akadémia Kémiai Kutatóközpont Kémiai Intézet, Biooxidációs csoport, Budapest. krisz@chemres.hu
Jenei
Veronika
V
von Bölcsházy
Gábor
G
Somogyi
Anikó
A
Jakus
Judit
J
D000375:Aging / Q000378:metabolism*; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000378:metabolism*; D003925:Diabetic Angiopathies / Q000378:metabolism*; D003928:Diabetic Nephropathies / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000378:metabolism; D005609:Free Radicals / Q000378:metabolism*; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D030421:Peroxynitrous Acid / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D026361:Reactive Nitrogen Species / Q000378:metabolism*; D019459:Urothelium / Q000378:metabolism
D005609:Free Radicals; D026361:Reactive Nitrogen Species; D030421:Peroxynitrous Acid; D009569:Nitric Oxide