The effect of PDE5 inhibitors on bone and oxidative damage in ovariectomy-induced osteoporosis
The effect of PDE5 inhibitors on bone and oxidative damage in ovariectomy-induced osteoporosis
复制标题
DOI：
10.1177/1535370217703352
复制
发表时间：
2017-05-01
影响因子：
3.2
通讯作者：
Sekeroglu, Mehmet R.
中科院分区：
文献类型：
--
作者：
Alp, Hamit H.;Huyut, Zubeyir;Sekeroglu, Mehmet R.
骨质疏松症是一个与多种因素相关的重大公共卫生问题，影响着50%以上的50岁以上女性。在本研究中，我们的目的是通过一氧化氮/3 '，5'-环磷酸鸟苷/蛋白激酶G信号通路研究磷酸二酯酶-5抑制剂对骨质疏松症的影响。将50只雌性白化病Wistar大鼠分为5组。第一组为健康对照组，不做卵巢切除术。其他组中的所有动物均接受双侧卵巢切除术。卵巢切除术后6个月，第3、4和5组分别给予伐地那非、乌地那非和他达拉非，但阳性对照组不给予（10 mg/kg/天，持续2个月）。在卵巢切除术前后以及治疗后，使用骨密度测定仪测定所有组的骨密度值。用酶联免疫吸附法测定血浆中一氧化氮、内皮型一氧化氮合酶、不对称二甲基精氨酸、3 '，5'-环磷酸鸟苷、蛋白激酶G、磷酸二酯酶-5、吡啶啉、脱氧吡啶啉、I型胶原羧基端肽片段和羧基端前肽的水平。采用高效液相色谱法测定丙二醛、8-羟基-2-脱氧鸟苷、脱氧鸟苷和辅酶Q10的水平。此外，测量各组右侧股骨松质骨密度和骺板。组织学上观察到骨组织中的血管生成。此外，我们确定抑制剂可能对骨密度增加和骨吸收标志物减少产生积极影响。我们还观察到这些抑制剂对氧化应激的积极影响。总之，这些磷酸二酯酶-5抑制剂增加了骨组织中的血管生成，提高了骨质疏松症大鼠骨的重建率。（PubChem CID：6918523）;他达拉非（PubChem CID：110635）;伐地那非（PubCham CID：110634）。影响声明我们的研究结果似乎建立了骨质疏松症模型，并提供了三种单独的PDE 5抑制剂的积极作用的证据。（伐地那非、乌地那非和他达拉非）。研究了这些PDE 5抑制剂的积极作用，并通过骨质量密度和骨吸收标志物证实。这些影响与显着的抗氧化活性有关。骨质疏松症是一个重大的公共卫生问题，特别是在老年人群中。在识别和理解这种疾病的新的潜在治疗方式方面取得了重大进展。这项研究提供了这样一个进步。
Osteoporosis is a major public health problem associated with many factors, and it affects more than 50% of women over 50 years old. In the current study, our purpose was to investigate the effects of phosphodiestarase-5 inhibitors on osteoporosis via the nitric oxide/3',5'-cyclic guanosine monophosphate/protein kinase G signalling pathway. A total of 50 female albino Wistar rats were separated into five groups. The first group was appointed as the healthy control group with no ovariectomy. All animals in the other groups underwent a bilateral ovariectomy. Six months after the ovariectomy, vardenafil, udenafil and tadalafil were given to the third, fourth and fifth groups, respectively, but were not administered to the positive control group (10 mg/kg per day for two months). The bone mineral density values were determined using a densitometry apparatus for all groups pre- and post-ovariectomy as well as after treatment. The levels of nitric oxide, endothelial nitric oxidesynthase, asymmetric dimethylarginine, 3',5'-cyclic guanosine monophosphate, protein kinase G, phosphodiestarase-5, pyridinoline, deoxypyridinoline, carboxyterminal telopeptide fragments and plasma carboxy terminal propeptide of type I collagen were determined using an enzyme linked immunosorbent assay. The levels of malondialdehyde, 8-hydroxy-2-deoxy guanosine, deoxyguanosine and coenzyme Q10 were determined by a high-performance liquid chromatography assay. Additionally, the right femoral trabecular bone density and the epiphyseal plate were measured in all groups. Angiogenesis was histologically observed in the bone tissue. In addition, we determined that the inhibitors may have caused a positive impact on the increased bone mass density and reduction of bone resorption markers. We also observed the positive effects of these inhibitors on oxidative stress. In conclusion, these phosphodiestarase-5 inhibitors increase angiogenesis in bone tissue and improve the re-formation rate of bone in rats with osteoporosis.Chemical compounds studied in this articleUdenafil (PubChem CID: 6918523); Tadalafil (PubChem CID: 110635); Vardanafil (PubCham CID: 110634).Impact statementThe results in our study appear to establish the osteoporosis model and provide evidence of the positive effects of three separate PDE5 inhibitors (vardenafil, udenafil, and tadalafil). The positive effects of these PDE5 inhibitors are investigated and demonstrated by the bone mass density and bone resorption markers. These effects are associated with significant demonstrated antioxidant activities. Osteoporosis is a significant major public health problem especially in more aged populations. Advances in identifying and understanding new potential therapeutic modalities for this disease are significant. This study provides such an advance.