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Purpose: 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., Materials and 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., (Copyright (c) 2010 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: Nrf2 (nuclear factor-E2 related factor-2), nuclear factor-kappaB and mitogen-activated protein kinase, including extracellular regulated kinase, c-jun N-terminal kinase and p38 mitogen-activated protein kinase, are crucial for signal transduction. We previously reported that heme oxygenase-1 over expression induced by the heme oxygenase-1 inducer hemin protected testes from torsion-detorsion injury. In this study we elucidated which of these enzymes is involved in hemin induced heme oxygenase-1 over expression in testicular tissues after torsion-detorsion injury., Materials and Methods: Adult male Sprague-Dawley rats (National Science Council, Taipei, Taiwan, Republic of China) were allocated to undergo testicular torsion-detorsion immediately followed by injection of normal saline, hemin or hemin plus tin protoporphyrin, a heme oxygenase-1 inhibitor. Another set of rats that underwent sham operation were used as controls. Testes were harvested 0 and 30 minutes after detorsion and enzyme expression was analyzed., Results: Hemin alone caused no significant effects on the expression of Nrf2, nuclear factor-kappaB, extracellular regulated kinase and c-jun N-terminal kinase. Similarly testicular torsion-detorsion injury caused no significant effects on Nrf2 expression. In the presence of torsion-detorsion injury hemin significantly up-regulated Nrf2 expression. Moreover, this effect was not affected by tin protoporphyrin. Unlike Nrf2, the expression of nuclear factor-kappaB, extracellular regulated kinase and c-jun N-terminal kinase was significantly up-regulated by testicular torsion-detorsion. Hemin significantly attenuated the testicular torsion-detorsion induced up-regulation of nuclear factor-kappaB and extracellular regulated kinase but not c-jun N-terminal kinase. The effects of hemin on nuclear factor-kappaB and extracellular regulated kinase were significantly reversed by tin protoporphyrin. However, the expression of p38 mitogen-activated protein kinase in rodent testes was not affected by these interventions., Conclusions: Hemin induced heme oxygenase-1 over expression in rodent testes after torsion-detorsion injury involves Nrf2, nuclear factor-kappaB and extracellular regulated kinase.

Purpose: Testicular torsion-detorsion has been identified as an ischemia-reperfusion type of injury. We elucidated the protective role of heme oxygenase-1 super induction on testicular torsion-detorsion injury., Materials and Methods: Adult male Sprague-Dawley rats were randomly allocated to undergo testicular torsion-detorsion, immediately followed by injection of normal saline, the heme oxygenase-1 inducer hemin or hemin plus the heme oxygenase-1 inhibitor tin protoporphyrin. Another set of rats that underwent sham operation, immediately followed by injection of normal saline, hemin or hemin plus tin protoporphyrin, served as controls. Testes were harvested 4 and 24 hours after detorsion, respectively, in the experimental groups or at comparable time points in the control groups., Results: Histological evaluation confirmed that torsion-detorsion caused significant testicular tissue injury. Torsion-detorsion also caused significant increases in the testicular levels of nitric oxide, malondialdehyde, myeloperoxidase activity and heme oxygenase-1. The heme oxygenase-1 inducer hemin significantly enhanced the heme oxygenase-1 expression induced by torsion-detorsion and in turn attenuated testicular injury, and increases in nitric oxide, malondialdehyde and myeloperoxidase activity. In addition, the protective effects of hemin were significantly offset by the heme oxygenase-1 inhibitor tin protoporphyrin., Conclusions: Super induction of heme oxygenase-1 protects testes from torsion-detorsion injury.