Nitrosative stress and glutathione redox system in four different tissues of alloxan-induced hyperglycemic animals

Abstract

In hyperglycemia a reduction of the antioxidant power and an increased production of nitric oxide (NO) have been reported. Because nitrotyrosine (NT) is a stable end-product of nitrosative stress, assessment of its concentration is considered a useful marker of NO-dependent damages. The level of nitrotyrosine and four antioxidant parameters were evaluated in pancreas, kidney, heart, and testis of alloxan-induced hyperglycemic rabbits after 6 and 10 weeks of persistent hyperglycemia. In hyperglycemic groups, the level of nitrotyrosine was elevated by 44 and 39%, 92 and 95%, and by 155 and 138% in pancreas, kidney, and heart, respectively, while the testicular level of NT was unaffected. The pancreatic activities of glutathione peroxidase (GPX) and catalase (CAT) increased by 64% and 50%, and by 49 and 70%, while the level of glutathione (GSH) and the activity of glutathione reductase (GR) decreased by 37 and 38%, and by 57 and 42%. In the kidney the significant changes occurred as decreases in GR activity and GSH level by 36 and 35%, and by 28 and 23%, respectively. In the heart, a significant increase in CAT activity by 90 and 23% was observed. In the testis, the CAT, GPX, and GR activities were increased by 67 and 77%, 72 and 27%, and 33 and 28%, respectively, while the level of GSH was increased by 22 and 17%. These results confirm that tissues from hyperglycemic animals differ in neutralizing nitrosative stress. This may be due to different adaptive responses of their glutathione redox cycle.