Dipyridamole and dilazep suppress oxygen radicals in puromycin aminonucleoside nephrosis rats.
BACKGROUND
Reactive oxygen species (ROS) are involved in the pathophysiology of puromycin aminonucleoside (PAN) nephrosis. To elucidate further the role of radicals in PAN nephrosis and the to determine the particular radical species scavenged by dipyridamole (DPM) and dilazep (DZ), we applied chemiluminescence and electron spin resonance (ESR) techniques.


METHODS
Chemiluminescence of glomeruli, which were isolated on day 7 from rats injected with 100 mg kg-1 PAN, was measured with or without scavengers. The inhibitory effects of DPM and DZ on hydroxyl radical adduct formation in the Fenton's reaction were evaluated using ESR.


RESULTS
Chemiluminescence was greater in glomeruli from rats with PAN nephrosis than in the the glomeruli of control rats. This increase was suppressed by superoxide dismutase, catalase, dimethylthiourea and also by DPM and DZ. ESR indicated that DPM and DZ inhibited hydroxyl radical adduct formation with a second-order rate constant of 2.9 x 10(10) and 1.6 x 10(10) (mol L(-1) s(-1) respectively, similar to that of dimethylthiourea.


CONCLUSIONS
DPM and DZ scavenge hydroxyl radicals, thereby alleviating PAN nephrosis.
Nakamura
K
K
Teikyo University School of Medicine, Tokyo.
Kojima
K
K
Arai
T
T
Shirai
M
M
Usutani
S
S
Akimoto
H
H
Masaoka
H
H
Nagase
M
M
Yamamoto
M
M
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000633:toxicity; D004109:Dilazep / Q000494:pharmacology*; D004176:Dipyridamole / Q000494:pharmacology*; D004578:Electron Spin Resonance Spectroscopy; D016166:Free Radical Scavengers / Q000494:pharmacology; D005609:Free Radicals / Q000378:metabolism; D017665:Hydroxyl Radical / Q000378:metabolism; D007678:Kidney Glomerulus / Q000187:drug effects / Q000378:metabolism; D008163:Luminescent Measurements; D008297:Male; D009401:Nephrosis / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism*; D011692:Puromycin Aminonucleoside / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000494:pharmacology; D013997:Time Factors
D000903:Antibiotics, Antineoplastic; D016166:Free Radical Scavengers; D005609:Free Radicals; D017382:Reactive Oxygen Species; D017665:Hydroxyl Radical; D011692:Puromycin Aminonucleoside; D004176:Dipyridamole; D013482:Superoxide Dismutase; D004109:Dilazep