Sesamol Protects Testis from Ischemia-Reperfusion Injury through Scavenging Reactive Oxygen Species and Upregulating CREM<i>τ</i> Expression
Siming Wei, Rongyun Wang, Yansong Chen
Abstract
Testicular torsion/detorsion-induced damage is considered as a typical ischemia-reperfusion injury attributed to excessive reactive oxygen species (ROS) production. ROS may regulate many genes whose expression affects cell-cycle regulation, cell proliferation, and apoptosis. The cAMP-responsive element modulator- τ (CREM τ ) gene expression in the testis is essential for normal germ cell differentiation. The present study was aimed at investigating the effect of sesamol, a powerful antioxidant, on testicular ischemia-reperfusion injury and related mechanisms in an experimental testicular torsion-detorsion rat model. The type of our study was a randomized controlled trial. Sixty rats were randomly divided into the following 3 groups: (1) sham-operated control group (<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M1"><mml:mi>n</mml:mi><mml:mo>=</mml:mo><mml:mn>20</mml:mn></mml:math>), (2) testicular ischemia-reperfusion group (<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M2"><mml:mi>n</mml:mi><mml:mo>=</mml:mo><mml:mn>20</mml:mn></mml:math>), and (3) testicular ischemia-reperfusion+sesamol-treated group (<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M3"><mml:mi>n</mml:mi><mml:mo>=</mml:mo><mml:mn>20</mml:mn></mml:math>). Testicular ischemia-reperfusion was induced by left testicular torsion (720° rotation in a counterclockwise direction) for 2 hours, followed by detorsion. Orchiectomy was performed at 4 hours or 3 months after detorsion. The testis was obtained for the analysis of the following parameters, including malondialdehyde level (a sensitive indicator of ROS), CREM τ expression, and spermatogenesis. In the testicular ischemia-reperfusion group, the malondialdehyde level was significantly increased with a concomitant significant decrease in CREM τ expression and spermatogenesis in ipsilateral testis. These results suggest that overproduction of ROS after testicular ischemia-reperfusion may downregulate CREM τ expression, which causes spermatogenic injury. Sesamol treatment resulted in a significant reduction in the malondialdehyde level and significant increase in CREM τ expression and spermatogenesis in ipsilateral testis. These data support the above suggestion. Our study shows that sesamol can attenuate testicular ischemia-reperfusion injury through scavenging ROS and upregulating CREM τ expression.