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. MATERIALS AND 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. CONCLUSION: These results indicate that edaravone reduces the oxidative stress and prevents the testicular damage induced by I-R.

Acute urinary retention and subsequent catheterization cause lipid peroxidation and oxidative DNA damage in the bladder: preventive effect of edaravone, a free-radical scavenger.

OBJECTIVE: To investigate the effect of a free-radical scavenger, edaravone, on the changes occurring with acute urinary retention (AUR) and subsequent catheterization in the rat bladder. MATERIALS AND METHODS: Eight-week-old male Sprague Dawley rats were allocated to one of four groups; an AUR group that had urinary retention induced, with subsequent catheterization; two edaravone groups, given edaravone at 1 or 10 mg/kg body weight for 60 min and then the same urinary retention and subsequent catheterization; and a sham-operated control group given edaravone 10 mg/kg. Urinary retention was induced by the clamping the rat penile urethra with a small clip, making a cystostomy, and then infusing 3 mL (0.6 mL/min) of saline with an infusion pump. The obstruction was sustained for 30 min and then the bladder was allowed to drain with a catheter in place for 60 min as the studies continued. After killing the rats the function of the bladder was assessed, with carbachol and 100 mM KCl, and the levels of malondialdehyde (MDA, a marker of lipid peroxidation), 8-hydroxydeoxyguanosine (8-OHdG; a marker of oxidative DNA damage), heat-shock protein 70 (HSP 70) and its mRNA were measured. RESULTS: AUR increased the intravesical pressure and decreased blood flow, and subsequent catheterization decreased the intravesical pressure and increased blood flow. Edaravone induced a decrease in blood flow in the bladder during the urinary retention and subsequent catheterization compared to the blood flow in the AUR group. Edaravone resulted in protection of the contractile responses to both carbachol and KCl in a dose-dependent manner. The MDA concentration, 8-OHdG content and expressions of HSP-70 and its mRNA in the AUR group were significantly larger than those of the control group. Edaravone markedly suppressed the accumulations of MDA and 8-OHdG in the bladder, and reduced the expressions of HSP 70 and its mRNA. CONCLUSION: These results indicate that edaravone reduces the oxidative stress and prevents the bladder dysfunction caused by AUR and subsequent catheterization.