8-hydroxy-2--deoxyguanosine and Nephritis--Interstitial

It is well known that oxidative stress is related to the pathogenesis of adriamycin (ADR) nephropathy. However, it is unclear how nitric oxide (NO) is associated with the pathophysiological process after ADR administration. The NO level in a kidney homogenate was assayed by electron paramagnetic resonance (EPR) spectrometry using a direct in vivo NO trapping technique after ADR administration. N-(3-(aminomethyl)benzyl)acetamidine (1400W) was used as a specific, inducible nitric oxide synthase (iNOS) inhibitor. The levels of NO after ADR administration gradually increased for 6 h and then decreased until 24 h after ADR administration. The fractional excretion of Na (FE(Na)) in the urine was elevated in the ADR group on day 1. Pre-treatment of the animals with 1400W attenuated the increase in NO levels despite further elevation of FE(Na). These findings suggest that iNOS-derived NO does not produce a harmful effect but rather protects the ADR-treated kidney against sodium excretion.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Amidines; Animals; Benzylamines; beta-N-Acetylhexosaminidases; Deoxyguanosine; Doxorubicin; Electron Spin Resonance Spectroscopy; Enzyme Inhibitors; Kidney; Male; Nephritis, Interstitial; Nitrates; Nitric Oxide; Nitric Oxide Synthase Type II; Nitrites; Rats

Oxidative stress is at play in the progression of chronic renal failure (CRF) and in the genesis of atherosclerosis. The aim of the present study was to evaluate the factors that might influence the oxidative-antioxidative balance in patients on hemodialysis. The study group consisted of 71 hemodialysis patients due to CRF. Sixteen healthy subjects constituted a control group. The levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG), C-reactive protein (CRP), and the blood lipid profile were measured in both groups. The results showed significantly higher mean levels of both 8-OHdG and CRP in the hemodialysis patients compared with that in the control subjects. The highest level of 8-OHdG was found in the subgroups of the patients with CRF primarily caused by diabetes (16.4 ng/ml) and with hypertensive nephropathy (15.8 ng/ml). More than a 2.5-fold higher level of 8-OHdG in the hemodialysis patients compared with the control subjects points to the presence of intensive oxidative stress in the patients.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Aged; C-Reactive Protein; Deoxyguanosine; Diabetes Complications; Glomerulonephritis; Humans; Hypertension; Kidney Failure, Chronic; Middle Aged; Nephritis, Interstitial; Oxidative Stress; Renal Dialysis

Oxidative stress is an important pathogenetic factor in underlying diabetic complications. Recently, 8-hydroxy-2'-deoxyguanosine (8-OHdG) has been reported to serve as a new sensitive biomarker of the oxidative DNA damage in vivo. We studied the relationship between oxidative DNA damage and tubulointerstitial injury in patients with diabetic nephropathy.. Type 2 diabetic patients (n = 25) and healthy control subjects (n = 20) were studied. The urine concentrations of 8-OHdG were measured by a competitive ELISA. The severity of the glomerular changes was graded using Gellman's criteria, and the severity of the tubulointerstitial lesions was determined by a semiquantitative estimate of the space occupied by the fibrous tissue and/or interstitial infiltrates.. The urinary 8-OHdG excretion were significantly higher in the diabetics than in the healthy controls, and tended to increase with severity of the glomerular diffuse lesion, but it was not significant. The urinary 8-OHdG excretion significantly increased with severity of the tubulointerstitial lesion.. Oxidative stress may contribute to the progression of tubulointerstitial injury in patients with diabetic nephropathy.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Biomarkers; Deoxyguanosine; Diabetic Nephropathies; Disease Progression; DNA Damage; Female; Humans; Male; Middle Aged; Nephritis, Interstitial; Oxidative Stress