Effect of a novel free radical scavenger, edaravone, on puromycin aminonucleoside induced nephrosis in rats.
Recent studies indicate that excessive production of oxidants plays a role in the pathogenesis of glomerular injury leading to proteinuria in patients with minimal-change nephrotic syndrome (MCNS). The novel free radical scavenger, edaravone (EDA), which was recently developed in Japan, is currently used in patients with stroke. We studied whether this new agent would be beneficial in patients with MCNS by its antioxidant activity and examined its effect on proteinuria in nephrosis induced by puromycin-aminonucleoside (PAN) in rats. Nineteen Wistar-Kyoto rats injected with PAN were assigned to four groups: group 1, without EDA (n=4); group 2, concomitant EDA injection from 1 day prior to PAN administration (n=5); group 3, concomitant EDA injection from 1 day after PAN administration (n=5); group 4, concomitant EDA injection from 3 days after PAN administration (n=5). Daily urinary excretions of protein and 8-hydroxy-2'-deoxyguanosine (8-OHdG), a new sensitive marker of oxidative DNA damage in vivo, were measured in each group from the 1st to the 30th day after PAN injection. In group 1 proteinuria developed from the 5th day and reached the peak level on the 9th day. In groups 2, 3, and 4 proteinuria did not appear until the 6th day. The excretions in urinary protein and 8-OHdG were significantly lower in groups 2, 3, and 4 than group 1 on days 5, 9, and 25. In conclusion, EDA could delay and ameliorate the urinary protein excretion in accordance with the urinary 8-OHdG excretion in PAN-induced nephrosis.
Someya
Tomonosuke
T
Department of Pediatrics, School of Medicine, Juntendo University, Tokyo, Japan.
Kaneko
Kazunari
K
Yamada
Toshiyuki
T
Yamashiro
Yuichiro
Y
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D000983:Antipyrine / Q000031:analogs & derivatives* / Q000494:pharmacology; D015415:Biomarkers / Q000652:urine; D004249:DNA Damage; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000652:urine; D000077553:Edaravone; D005260:Female; D016166:Free Radical Scavengers / Q000494:pharmacology*; D009401:Nephrosis / Q000139:chemically induced* / Q000652:urine*; D010084:Oxidation-Reduction; D011507:Proteinuria / Q000209:etiology / Q000652:urine; D011692:Puromycin Aminonucleoside; D051381:Rats; D011921:Rats, Inbred WKY; D013997:Time Factors
D015415:Biomarkers; D016166:Free Radical Scavengers; D011692:Puromycin Aminonucleoside; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine; D000077553:Edaravone; D000983:Antipyrine