Department of Urology, Mustafa Kemal University, Tayfur Ata Sökmen Medical School, Hatay, Turkey.
Hum Exp Toxicol. 2011 Aug;30(8):897-903. doi: 10.1177/0960327110382564. Epub 2010 Sep 2.
Thymoquinone is the major active component derived from Nigella sativa. Methotrexate is a folic acid antagonist widely used in clinic. Aim of this study was to investigate the possible protective role of thymoquinone on testicular toxicity of methotrexate. Experiments were performed on male C57BL/6 mice (6 weeks old, 20 ± 2 g). The animals were divided into four groups with six mice in each group. Equivalent volumes of saline were injected intraperitoneally (i.p.) in the control group. In the thymoquinone group, mice received thymoquinone i.p. with a dose of 10 mg/kg/day for 4 days. Mice in the methotrexate group received single dose of methotrexate i.p., with a dose of 20 mg/kg. Finally, in the methotrexate plus thymoquinone group, in the first and the following 3 days after methotrexate administration, thymoquinone was injected with a dose of 10 mg/kg/day, i.p. At the end of the experiment, the left testis was quickly removed and divided into two parts for histological examination and biochemical analysis. Methotrexate alone increased total antioxidant capacity and myeloperoxidase activity compared to the controls. Thymoquinone treatment decreased total antioxidant capacity and prevented the increase in the myeloperoxidase activity. Light microscopy showed in mice that receiving methotrexate resulted in interstitial space dilatation, edema, severe disruption of the seminiferous epithelium and reduced diameter of the seminiferous tubules. Administration of thymoquinone reversed histological changes of methotrexate significantly. We suggest that thymoquinone use may decrease the destructive effects of methotrexate on testicular tissue of patients using this agent.
姜黄素是从黑种草中提取的主要活性成分。甲氨蝶呤是一种广泛应用于临床的叶酸拮抗剂。本研究旨在探讨姜黄素对甲氨蝶呤睾丸毒性的可能保护作用。实验在雄性 C57BL/6 小鼠（6 周龄，20±2 g）上进行。动物分为四组，每组 6 只。对照组腹腔注射等体积生理盐水。姜黄素组腹腔注射姜黄素，剂量为 10mg/kg/天，连续 4 天。甲氨蝶呤组单次腹腔注射甲氨蝶呤，剂量为 20mg/kg。最后，在甲氨蝶呤加姜黄素组中，在甲氨蝶呤给药后的第 1 天和随后的 3 天内，腹腔注射姜黄素，剂量为 10mg/kg/天。实验结束时，迅速取出左侧睾丸，分为两部分进行组织学检查和生化分析。与对照组相比，甲氨蝶呤单独使用可增加总抗氧化能力和髓过氧化物酶活性。姜黄素处理可降低总抗氧化能力并防止髓过氧化物酶活性增加。光镜下观察到，接受甲氨蝶呤治疗的小鼠出现间质空间扩张、水肿、生精上皮严重破坏和生精小管直径减小。姜黄素的给药显著逆转了甲氨蝶呤引起的组织学变化。我们认为，姜黄素的使用可能会降低该药物患者睾丸组织中甲氨蝶呤的破坏性作用。
