Protective effect of edaravone, a free-radical scavenger, on ischaemia-reperfusion injury in the rat testis.
OBJECTIVE
To investigate the effect of edaravone, a radical scavenger, on ischaemia-reperfusion (I-R) injury in the testes.


METHODS
Eight-week-old male Sprague-Dawley rats were allocated to one of four groups: a no-drug group subjected to induction of 30-min of ischaemia and 60-min reperfusion; two drug groups administered edaravone at 1 or 10 mg/kg intraperitoneal and then subjected to 30-min ischaemia and 60-min reperfusion; and a sham-operated control group administered edaravone at 10 mg/kg intraperitoneal. To induce testicular I-R, the right testis was exposed outside of the body and the testicular artery was clamped with a small clip for 30 min. Blood flow and nitric oxide (NO) release were monitored in real time simultaneously with a laser Doppler flowmeter and an NO-selective electrode, respectively. After death the tissue levels of NO(2)-NO(3) (a marker of NO production), malondialdehyde (a marker of lipid peroxidation), 8-hydroxydeoxyguanosine (a marker of oxidative DNA damage), myeloperoxidase (a marker of neutrophil infiltration), and heat-shock protein 70 (HSP 70) and its mRNA were measured. The testicular tissue was also analysed histologically.


RESULTS
Clamping the testicular artery resulted in a decrease of blood flow to 0-5% of the basal level measured before clamping. NO release was increased during clamping and gradually recovered to the basal level on removing the clip. Interestingly, the peak of NO release in rats of the no-drug group occurred at the start of reperfusion, while that in the high-dose drug group occurred several minutes later. The levels of NO(2)-NO(3), malondialdehyde, 8-hydroxydeoxyguanosine, myeloperoxidase and HSP 70 and its mRNA, and histological variables, were significantly greater in the no-drug I-R group than in the control, and these variables were ameliorated by treatment with edaravone.


CONCLUSIONS
These results indicate that edaravone reduces the oxidative stress and prevents the testicular damage induced by I-R.
Tamamura
Mayuko
M
Department of Pathophysiological and Therapeutic Science, Tottori University Yonago, Japan.
Saito
Motoaki
M
Kinoshita
Yukako
Y
Shimizu
Shogo
S
Satoh
Itaru
I
Shomori
Kohei
K
Dimitriadis
Fotios
F
Satoh
Keisuke
K
D000818:Animals; D000983:Antipyrine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000077553:Edaravone; D016166:Free Radical Scavengers / Q000627:therapeutic use*; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000473:pathology; D013086:Spermatic Cord Torsion / Q000188:drug therapy*; D013737:Testis / Q000098:blood supply / Q000473:pathology*
D016166:Free Radical Scavengers; D000077553:Edaravone; D000983:Antipyrine