Protective effect of sivelestat, a neutrophil elastase inhibitor, on ipsilateral and contralateral testes after unilateral testicular ischaemia-reperfusion injury in rats.
OBJECTIVE
To investigate the effect of a neutrophil elastase inhibitor, sivelestat sodium hydrate, on testicular ischaemia-reperfusion (IR)-injury.


METHODS
Eight-week-old male Sprague-Dawley rats were divided into four groups: sham-operated control rats; IR rats (group IR); and IR rats that received intra-abdominal administration of 15 mg/kg or 60 mg/kg sivelestat (group IR15 and group IR60, respectively). Right testicular vessels were clamped for 90 min in groups IR, IR15 and IR60. Sivelestat had been administered 45 min after the induction of the ischaemia in groups IR15 and IR60. In subpopulations of IR, IR15 and IR60 rats, reperfusion was performed after ischaemia for 2 h (groups IR-A, IR15-A and IR60-A, respectively) or 48 h (groups IR-B, IR15-B and IR60-B, respectively). At the end of the reperfusion period, blood samples were aspirated from both spermatic veins of each rat and testosterone was evaluated. Then both testes from all rats were collected and tissue levels of malondialdehyde (MDA), myeloperoxidase (MPO), and heat-shock protein-70(HSP-70) were evaluated. Testicular tissue samples were also processed for histological evaluation and TUNEL staining.


RESULTS
MDA, MPO and HSP-70 levels in the ischemic testis were significantly higher in the IR group compared with the control group. MDA and HSP-70 in the contralateral testis were significantly higher in the IR group compared with the control group. Bilateral testosterone levels were lower in all rat groups in comparison with the control group. Bilateral testicular samples in group IR showed extensive histopathologic degenerative alterations and increased percentage of apoptotic cells. Sivelestat treatment lowered the MDA concentration and the percentage of apoptotic cells bilaterally and ameliorated the testicular histological pattern bilaterally.


CONCLUSIONS
Unilateral testicular ischaemia causes significant contralateral testicular damage. Sivelestat may be a novel adjunct tool for reducing oxidative stress and partially preventing bilateral testicular damage.
Tsounapi
Panagiota
P
Division of Urology, Department of Surgery, Tottori University Faculty of Medicine, Yonago, Japan.
Saito
Motoaki
M
Dimitriadis
Fotios
F
Shimizu
Shogo
S
Kinoshita
Yukako
Y
Shomori
Kohei
K
Satoh
Itaru
I
Satoh
Keisuke
K
D000818:Animals; D005998:Glycine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D008297:Male; D009195:Peroxidase / Q000378:metabolism; D053491:Proteinase Inhibitory Proteins, Secretory / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D013449:Sulfonamides / Q000627:therapeutic use*; D013737:Testis / Q000098:blood supply*; D013739:Testosterone / Q000378:metabolism
D018840:HSP70 Heat-Shock Proteins; D053491:Proteinase Inhibitory Proteins, Secretory; D013449:Sulfonamides; D013739:Testosterone; C069195:sivelestat; D009195:Peroxidase; D005998:Glycine