Baset Marwan Abdel, El Awdan Sally A, Khattab Marwa S, El-Marasy Salma A
Department of Pharmacology, Medical Research and Clinical Studies Institute, National Research Centre, Giza, Egypt.
Department of Pathology, Faculty of Veterinary Medicine, Cairo University, Giza, Egypt.
Sci Rep. 2025 Jul 29;15(1):27711. doi: 10.1038/s41598-025-10395-2.
This study investigated the protective effects of Rivaroxaban (RVX) against testicular ischemia-reperfusion (IR) injury in rats with a secondary aim of studying the involvement of hypoxia-inducible factor1-alpha testicular protection against ischemic insults. Twenty-four male rats were divided into four groups: sham control, testicular IR, and two RVX treatment groups (7 and 14 mg/kg) administered for one week prior to IR. Testicular IR led to significant impairment in testicular function, evidenced by an 86.5% reduction in testosterone levels and marked oxidative stress with an 189.3% increase in malondialdehyde (MDA). IR injury also triggered substantial elevations in apoptotic markers (271% increase in Bax (Bcl2-associated X protein) and 65.9% decrease in BCL2 (B-cell lymphoma 2), and inflammatory mediators (285.7% increase in NFκB (nuclear factor-kappa B). Additionally, angiogenic markers showed dramatic increases, with VEGF (vascular endothelial growth factor) and HIF-1 (Hypoxia inducible factor-1) rising by 431.8% and 519%, respectively. RVX treatment demonstrated dose-dependent protective effects, with the 14 mg/kg dose showing superior outcomes compared to 7 mg/kg. The higher dose significantly improved hormonal function (486.8% increase in testosterone), reduced oxidative stress (51.8% reduction in MDA), modulated apoptotic markers (68.3% decrease in BAX, 159.1% increase in BCL2), and normalized angiogenic factors (71.8% reduction in HIF-1). In conclusion, RVX demonstrated significant therapeutic potential in protecting against testicular IR injury, with the 14 mg/kg dose showing optimal protective effects. Reduction in HIF-1α and VEGF protein expression mediated RVX's anti-oxidant, anti-inflammatory, and anti-apoptotic effect in rats subjected to testicular IR.
本研究调查了利伐沙班（RVX）对大鼠睾丸缺血再灌注（IR）损伤的保护作用，其次要目的是研究缺氧诱导因子1α在睾丸对缺血性损伤的保护作用中的参与情况。24只雄性大鼠分为四组：假手术对照组、睾丸IR组以及两个RVX治疗组（7和14mg/kg），在IR前一周给药。睾丸IR导致睾丸功能显著受损，表现为睾酮水平降低86.5%，氧化应激明显，丙二醛（MDA）增加189.3%。IR损伤还引发凋亡标志物大幅升高（Bax（Bcl2相关X蛋白）增加271%，BCL2（B细胞淋巴瘤2）降低65.9%）以及炎症介质升高（核因子κB（NFκB）增加285.7%）。此外，血管生成标志物显著增加，血管内皮生长因子（VEGF）和缺氧诱导因子-1（HIF-1）分别升高431.8%和519%。RVX治疗显示出剂量依赖性保护作用，14mg/kg剂量组的效果优于7mg/kg剂量组。较高剂量显著改善了激素功能（睾酮增加486.8%），降低了氧化应激（MDA降低51.8%），调节了凋亡标志物（BAX降低68.3%，BCL2增加159.1%），并使血管生成因子恢复正常（HIF-1降低71.8%）。总之，RVX在预防睾丸IR损伤方面显示出显著的治疗潜力，14mg/kg剂量显示出最佳保护效果。HIF-1α和VEGF蛋白表达的降低介导了RVX在睾丸IR大鼠中的抗氧化、抗炎和抗凋亡作用。
