Nitric oxide protection against adriamycin-induced tubulointerstitial injury.
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.
Oteki
Takaaki
T
International University of Health and Welfare, Nasushiobara, Tochigi, Japan. oteki@iuhw.ac.jp
Nagase
Sohji
S
Shimohata
Homare
H
Hirayama
Aki
A
Ueda
Atsushi
A
Yokoyama
Hidekatsu
H
Yoshimura
Tetsuhiko
T
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000578:Amidines / Q000494:pharmacology; D000818:Animals; D001596:Benzylamines / Q000494:pharmacology; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000652:urine; D004317:Doxorubicin; D004578:Electron Spin Resonance Spectroscopy; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007668:Kidney / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008297:Male; D009395:Nephritis, Interstitial / Q000139:chemically induced* / Q000188:drug therapy / Q000473:pathology; D009566:Nitrates / Q000652:urine; D009569:Nitric Oxide / Q000378:metabolism* / Q000652:urine; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors / Q000378:metabolism; D009573:Nitrites / Q000652:urine; D051381:Rats; D001619:beta-N-Acetylhexosaminidases / Q000652:urine
D000578:Amidines; D001596:Benzylamines; D004791:Enzyme Inhibitors; C104820:N-(3-(aminomethyl)benzyl)acetamidine; D009566:Nitrates; D009573:Nitrites; D009569:Nitric Oxide; D004317:Doxorubicin; D000080242:8-Hydroxy-2'-Deoxyguanosine; D052247:Nitric Oxide Synthase Type II; D001619:beta-N-Acetylhexosaminidases; D003849:Deoxyguanosine