title: The effect of PDE5 inhibitors on bone and oxidative damage in ovariectomy-induced osteoporosis.
abstract: 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.
authors.affiliation: 1 Faculty of Medicine, Department of Biochemistry, Yuzuncu Yil University, Van 65080, Turkey.
authors.forename: Hamit H
authors.initials: HH
authors.lastname: Alp
authors.affiliation: 1 Faculty of Medicine, Department of Biochemistry, Yuzuncu Yil University, Van 65080, Turkey.
authors.forename: Zübeyir
authors.initials: Z
authors.lastname: Huyut
authors.affiliation: 2 Faculty of Veterinary Medicine, Department of Pathology, Ataturk University, Erzurum 25240, Turkey.
authors.forename: Serkan
authors.initials: S
authors.lastname: Yildirim
authors.affiliation: 3 Faculty of Veterinary Medicine, Department of Internal Diseases, Yuzuncu Yil University, Van 65080, Turkey.
authors.forename: Yıldıray
authors.initials: Y
authors.lastname: Başbugan
authors.affiliation: 4 Faculty of Medicine, Department of Physical Medicine and Rehabilitation, Yuzuncu Yil University, Van 65080, Turkey.
authors.forename: Levent
authors.initials: L
authors.lastname: Ediz
authors.affiliation: 5 Faculty of Medicine, Department of Biochemistry, Sakarya University, Sakarya 54187, Turkey.
authors.forename: Mehmet R
authors.initials: MR
authors.lastname: Şekeroğlu
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000032:analysis; D015519:Bone Density; D001842:Bone and Bones / Q000473:pathology*; D002851:Chromatography, High Pressure Liquid; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D010024:Osteoporosis / Q000188:drug therapy*; D010052:Ovariectomy / Q000009:adverse effects*; D058986:Phosphodiesterase 5 Inhibitors / Q000008:administration & dosage*; D011743:Pyrimidines / Q000008:administration & dosage*; D017208:Rats, Wistar; D013449:Sulfonamides / Q000008:administration & dosage*; D000068581:Tadalafil / Q000008:administration & dosage*; D016896:Treatment Outcome; D000069058:Vardenafil Dihydrochloride / Q000008:administration & dosage*; D000096926:Benzenesulfonamides
chemical_list: D015415:Biomarkers; D058986:Phosphodiesterase 5 Inhibitors; D011743:Pyrimidines; D013449:Sulfonamides; D000068581:Tadalafil; D000069058:Vardenafil Dihydrochloride; C419664:udenafil; D000096926:Benzenesulfonamides
keywords: Bone loss; asymmetric dimethylarginine; bone mass density; nitric oxide signalling pathway; oxidative stress; tadalafil; udenafil; vardenfil