Alp Hamit H, Huyut Zübeyir, Yildirim Serkan, Başbugan Yıldıray, Ediz Levent, Şekeroğlu Mehmet R
1 Faculty of Medicine, Department of Biochemistry, Yuzuncu Yil University, Van 65080, Turkey.
2 Faculty of Veterinary Medicine, Department of Pathology, Ataturk University, Erzurum 25240, Turkey.
Exp Biol Med (Maywood). 2017 May;242(10):1051-1061. doi: 10.1177/1535370217703352. Epub 2017 Apr 11.
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 article Udenafil (PubChem CID: 6918523); Tadalafil (PubChem CID: 110635); Vardanafil (PubCham CID: 110634). Impact statement The 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.
骨质疏松症是一个与多种因素相关的重大公共卫生问题，它影响着超过50%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。总共50只雌性白化Wistar大鼠被分为五组。第一组被指定为未进行卵巢切除术的健康对照组。其他组的所有动物均接受双侧卵巢切除术。卵巢切除术后6个月，分别给第三、第四和第五组给予伐地那非、乌地那非和他达拉非，但不给阳性对照组用药（每天10mg/kg，持续两个月）。使用骨密度仪在所有组卵巢切除术前、术后以及治疗后测定骨矿物质密度值。使用酶联免疫吸附测定法测定一氧化氮、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型胶原羧基末端肽片段和血浆I型胶原羧基末端前肽的水平。使用高效液相色谱测定法测定丙二醛、8-羟基-2'-脱氧鸟苷、脱氧鸟苷和辅酶Q10的水平。此外，测量所有组右侧股骨小梁骨密度和骨骺板。对骨组织进行组织学观察血管生成情况。此外，我们确定这些抑制剂可能对骨量密度增加和骨吸收标志物减少产生了积极影响。我们还观察到这些抑制剂对氧化应激的积极作用。总之，这些磷酸二酯酶-5抑制剂增加了骨质疏松症大鼠骨组织中的血管生成并提高了骨的再形成率。本文研究的化合物 乌地那非（PubChem CID：6918523）；他达拉非（PubChem CID：110635）；伐地那非（PubCham CID：110634）。影响声明 我们研究的结果似乎建立了骨质疏松症模型，并提供了三种不同的磷酸二酯酶-5抑制剂（伐地那非、乌地那非和他达拉非）具有积极作用的证据。这些磷酸二酯酶-5抑制剂的积极作用通过骨量密度和骨吸收标志物进行了研究和证明。这些作用与显著的抗氧化活性相关。骨质疏松症是一个重大的公共卫生问题，尤其是在老年人群中。在识别和理解这种疾病的新潜在治疗方法方面取得进展具有重要意义。本研究提供了这样的进展。
