Sener Tarik Emre, Tavukcu Hasan Huseyin, Atasoy Beste Melek, Cevik Ozge, Kaya Ozlem Tugce, Cetinel Sule, Dagli Degerli Ayse, Tinay Ilker, Simsek Ferruh, Akbal Cem, Butticè Salvatore, Sener Goksel
Department of Urology, School of Medicine, Marmara University, Istanbul, Turkey.
Department of Urology, Istanbul Bilim University, Istanbul Florence Nightingale Hospital, Istanbul, Turkey.
Int J Impot Res. 2018 Aug;30(4):179-188. doi: 10.1038/s41443-018-0042-6. Epub 2018 Jul 5.
Radiotherapy (RT) for prostate cancer (PC) can cause erectile dysfunction (ED) by damaging neurovascular structures with oxidative stress. In this study, we evaluated the effects of resveratrol, an antioxidant, on post-RT ED. Fifty rats in five groups were evaluated; control (C), prostate-confined radiotherapy with short- and long-term vehicle or resveratrol treatment. Cavernosal tissues were obtained to analyze glutathione (GSH), nitric oxide (NO), cyclic guanosine monophosphate (cGMP), 8-hydroxy-2'-deoxy-guanosine (8-OHdG) levels and superoxide dismutase (SOD), caspase-3 activities, sirtuin-1, Foxo-3, nNOS, and eNOS protein expressions. Intracavernosal pressures (ICP) were measured for the long-term treatment group. In the RT + long-term vehicle treatment group, tissue GSH, NO, cGMP, and SOD activity were decreased while 8-OHdg levels and caspase-3 activities were increased. Radiotherapy caused a decrease in sirtuin-1, nNOS, and eNOS protein expressions. These parameters were reversed by resveratrol treatment. Foxo-3 protein expressions were unaltered in the RT + short-term vehicle treatment group and started to increase as a defense mechanism in the RT + long-term vehicle group; however, resveratrol treatment caused a significant increase in Foxo-3 expressions. Resveratrol preserved the metabolic pathways involved in erectile function and provided functional protection. Resveratrol can be used as a supplementary agent in patients undergoing radiotherapy to preserve erectile function.
前列腺癌(PC)的放射治疗(RT)可通过氧化应激损伤神经血管结构,从而导致勃起功能障碍(ED)。在本研究中,我们评估了抗氧化剂白藜芦醇对放疗后ED的影响。对五组共五十只大鼠进行了评估;对照组(C)、接受前列腺局限放疗并接受短期和长期载体或白藜芦醇治疗。获取海绵体组织以分析谷胱甘肽(GSH)、一氧化氮(NO)、环磷酸鸟苷(cGMP)、8-羟基-2'-脱氧鸟苷(8-OHdG)水平以及超氧化物歧化酶(SOD)、半胱天冬酶-3活性、沉默调节蛋白-1、叉头框蛋白O3(Foxo-3)、神经元型一氧化氮合酶(nNOS)和内皮型一氧化氮合酶(eNOS)蛋白表达。对长期治疗组测量海绵体内压(ICP)。在放疗+长期载体治疗组中,组织GSH、NO、cGMP和SOD活性降低,而8-OHdg水平和半胱天冬酶-3活性增加。放射治疗导致沉默调节蛋白-1、nNOS和eNOS蛋白表达下降。这些参数通过白藜芦醇治疗得到逆转。在放疗+短期载体治疗组中,Foxo-3蛋白表达未改变,而在放疗+长期载体组中作为一种防御机制开始增加;然而,白藜芦醇治疗导致Foxo-3表达显著增加。白藜芦醇保留了勃起功能所涉及的代谢途径并提供了功能保护。白藜芦醇可作为放疗患者的补充剂以保留勃起功能。