Simvastatin attenuates testicular injury induced by torsion-detorsion.
OBJECTIVE
The lipid lowering agent simvastatin has potent anti-oxidation capacity. We elucidated the potential of simvastatin to attenuate testicular injury induced by testicular torsion-detorsion. We also investigated simvastatin effects on nuclear factor-kappaB expression.


METHODS
We allocated 60 adult male Sprague-Dawley(R) rats to testicular torsion-detorsion, torsion-detorsion plus simvastatin (1 or 5 mg/kg), sham operation or sham operation plus simvastatin (5 mg/kg). There were 12 rats per group. Simvastatin was administered immediately after detorsion or immediately after sham operation. Testes were harvested 30 minutes and 24 hours after detorsion to facilitate the evaluation of nuclear factor-kappaB and testicular injury, respectively.


RESULTS
Histological findings revealed severe injury in testes of the torsion-detorsion and torsion-detorsion-simvastatin (1 mg/kg) groups while testes in the torsion-detorsion-simvastatin (5 mg/kg) group showed moderate injury. Myeloperoxidase activity, and cytokines, nitric oxide and malondialdehyde in testes in the torsion-detorsion-simvastatin (5 mg/kg) group were significantly lower than in the torsion-detorsion group. Values were comparable in the torsion-detorsion-simvastatin (1 mg/kg) and torsion-detorsion groups. Testicular concentrations of nuclear factor-kappaB in nuclear extracts and phosphorylated inhibitor-kappaB in cytosolic extracts in the torsion-detorsion-simvastatin (5 mg/kg) group were significantly lower than in the torsion-detorsion group. Values were comparable in the torsion-detorsion-simvastatin (1 mg/kg) and torsion-detorsion groups.


CONCLUSIONS
Simvastatin protected testes from torsion-detorsion injury in a dose dependent manner. Mechanisms may involve attenuating nuclear factor-kappaB activation and decreasing oxidative stress induced by torsion-detorsion.
Yang
Stone
S
Department of Urology, Mackay Memorial Hospital, Taipei, Taiwan, Republic of China.
Shih
Hung-Jen
HJ
Chow
Yung-Chiong
YC
Wang
Tao-Yeuan
TY
Tsai
Pei-Shan
PS
Huang
Chun-Jen
CJ
D000818:Animals; D000960:Hypolipidemic Agents / Q000627:therapeutic use*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D019821:Simvastatin / Q000627:therapeutic use*; D013086:Spermatic Cord Torsion / Q000150:complications*; D013737:Testis / Q000293:injuries* / Q000378:metabolism; D014947:Wounds and Injuries / Q000209:etiology / Q000517:prevention & control
D000960:Hypolipidemic Agents; D019821:Simvastatin