Hemin Induced Heme Oxygenase-1 Over Expression Involves Nuclear Factor-E2 Related Factor-2, Nuclear Factor-κB and Extracellular Regulated Kinase: An Experimental Study in a Testicular Torsion-Detorsion Rodent Model

Purpose: Nrf2 (nuclear factor-E2 related factor-2), nuclear factor-κB 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-κB, 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-κB, 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-κB and extracellular regulated kinase but not c-jun N-terminal kinase. The effects of hemin on nuclear factor-κB 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-κB and extracellular regulated kinase.