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Effects of edaravone against glomerular injury in rats with chronic puromycin aminonucleoside nephrosis

Tokushi Nakajima, Koichi Kanozawa, Tetsuya Mitarai
Department of Nephrology and Hypertension, Saitama Medical Center, Saitama Medical University

<Background> Excessive oxidants play roles in the pathogenesis of glomerular injury. Several studies have demonstrated protective effects of edaravone, a free radical scavenger, against renal injury. To clarify the protective effects of edaravone, we investigated changes in chemical markers of lipid peroxidation and renal histology in rats with chronic puromycin aminonucleoside (PAN) nephrosis (C-PAN).
<Methods>C-PAN was induced by intraperitoneal injections of PAN (130 mg/kg on day 1 and 60 mg/kg on day 14). Rats administered normal saline served as controls (n＝5). C-PAN rats were divided into two groups (each group: n＝4). In one group (C-PAN＋Eda), rats received 3.0 mg/kg/day of edaravone for five weeks. Blood and urinary samples were collected every week. Animals were sacrificed at the end of experiment for histological analysis.
<Results> In C-PAN＋Eda rats, urinary excretion of albumin and 8-isoPGF2α were significantly decreased compared with that in C-PAN rats (p＜0.01), whereas levels of urinary thiobarbituric acid-reactive substances (TBARS) did not differ between the two groups. On histological examination, the scores for glomerular injury and area positive for 4-HNE were significantly lower in C-PAN＋Eda than in C-PAN rats (p＜0.05, p＜0.01, respectively). Infiltration of macrophages was also suppressed in C-PAN＋Eda rats.
<Conclusion> Edaravone treatment of C-PAN was able to decrease albuminuria and to ameliorate glomerular injury. Levels of several markers related to oxidative stress and lipid peroxidation were reduced after treatment, accompanied by reduction of macrophage infiltration and decrease in apoptotic cells in the glomeruli. These findings indicate that edaravone has protective effects against the glomerular injury observed in C-PAN nephrosis.
J Saitama Medical University 2010; 37: 1-10
(Received February 23, 2009 / Accepted February 8, 2010)

Keywords: 1) oxidative stress, 2) puromycin aminonucleoside, 3) edaravone, 4) lipid peroxidation