Osteoprotective Effects in Postmenopausal Osteoporosis Rat Model: Oral Tocotrienol vs. Intraosseous Injection of Tocotrienol-Poly Lactic-Co-Glycolic Acid Combination

Osteoporosis, the most common bone disease, is associated with compromised bone strength and increased risk of fracture. Previous studies have shown that oxidative stress contributes to the progression of osteoporosis. Specifically, for postmenopausal osteoporosis, the reduction in estrogen levels l...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Nurul ‘Izzah Ibrahim, Hasnul ‘Iffah Mohd Noor, Ahmad Naqib Shuid, Sharlina Mohamad, Mohd Maaruf Abdul Malik, Putri Ayu Jayusman, Ahmad Nazrun Shuid, Isa Naina Mohamed
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	osteoporosis oxidative stress tocotrienol PLGA intraosseous Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/1430ba1163d045ebb27966a6258456e1
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:1430ba1163d045ebb27966a6258456e1
record_format	dspace
spelling	oai:doaj.org-article:1430ba1163d045ebb27966a6258456e12021-11-18T07:52:35ZOsteoprotective Effects in Postmenopausal Osteoporosis Rat Model: Oral Tocotrienol vs. Intraosseous Injection of Tocotrienol-Poly Lactic-Co-Glycolic Acid Combination1663-981210.3389/fphar.2021.706747https://doaj.org/article/1430ba1163d045ebb27966a6258456e12021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fphar.2021.706747/fullhttps://doaj.org/toc/1663-9812Osteoporosis, the most common bone disease, is associated with compromised bone strength and increased risk of fracture. Previous studies have shown that oxidative stress contributes to the progression of osteoporosis. Specifically, for postmenopausal osteoporosis, the reduction in estrogen levels leads to increased oxidative stress in bone remodeling. Tocotrienol, a member of vitamin E that exhibits antioxidant activities, has shown potential as an agent for the treatment of osteoporosis. Most studies on the osteoprotective effects of tocotrienols had used the oral form of tocotrienols, despite their low bioavailability due the lack of transfer proteins and high metabolism in the liver. Several bone studies have utilized tocotrienol combined with a nanocarrier to produce a controlled release of tocotrienol particles into the system. However, the potential of delivering tocotrienol–nanocarrier combination through the intraosseous route has never been explored. In this study, tocotrienol was combined with a nanocarrier, poly lactic-co-glycolic acid (PLGA), and injected intraosseously into the bones of ovariectomized rats to produce targeted and controlled delivery of tocotrienol into the bone microenvironment. This new form of tocotrienol delivery was compared with the conventional oral delivery in terms of their effects on bone parameters. Forty Sprague–Dawley rats were divided into five groups. The first group was sham operated, while other groups were ovariectomized (OVX). Following 2 months, the right tibiae of all the rats were drilled at the metaphysis region to provide access for intraosseous injection. The estrogen group (OVX + ESTO) and tocotrienol group (OVX + TTO) were given daily oral gavages of Premarin (64.5 mg/kg) and annatto-tocotrienol (60 mg/kg), respectively. The locally administered tocotrienol group (OVX + TTL) was given a single intraosseous injection of tocotrienol–PLGA combination. After 8 weeks of treatment, both OVX + TTO and OVX + TTL groups have significantly lower bone markers and higher bone mineral content than the OVX group. In terms of bone microarchitecture, both groups demonstrated significantly higher trabecular separation and connectivity density than the OVX group (p < 0.05). Both groups also showed improvement in bone strength by the significantly higher stress, strain, stiffness, and Young’s modulus parameters. In conclusion, daily oral tocotrienol and one-time intraosseous injection of tocotrienol–PLGA combination were equally effective in offering protection against ovariectomy-induced bone changes.Nurul ‘Izzah IbrahimHasnul ‘Iffah Mohd NoorAhmad Naqib ShuidSharlina MohamadMohd Maaruf Abdul MalikPutri Ayu JayusmanAhmad Nazrun ShuidIsa Naina MohamedFrontiers Media S.A.articleosteoporosisoxidative stresstocotrienolPLGAintraosseousTherapeutics. PharmacologyRM1-950ENFrontiers in Pharmacology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	osteoporosis oxidative stress tocotrienol PLGA intraosseous Therapeutics. Pharmacology RM1-950
spellingShingle	osteoporosis oxidative stress tocotrienol PLGA intraosseous Therapeutics. Pharmacology RM1-950 Nurul ‘Izzah Ibrahim Hasnul ‘Iffah Mohd Noor Ahmad Naqib Shuid Sharlina Mohamad Mohd Maaruf Abdul Malik Putri Ayu Jayusman Ahmad Nazrun Shuid Isa Naina Mohamed Osteoprotective Effects in Postmenopausal Osteoporosis Rat Model: Oral Tocotrienol vs. Intraosseous Injection of Tocotrienol-Poly Lactic-Co-Glycolic Acid Combination
description	Osteoporosis, the most common bone disease, is associated with compromised bone strength and increased risk of fracture. Previous studies have shown that oxidative stress contributes to the progression of osteoporosis. Specifically, for postmenopausal osteoporosis, the reduction in estrogen levels leads to increased oxidative stress in bone remodeling. Tocotrienol, a member of vitamin E that exhibits antioxidant activities, has shown potential as an agent for the treatment of osteoporosis. Most studies on the osteoprotective effects of tocotrienols had used the oral form of tocotrienols, despite their low bioavailability due the lack of transfer proteins and high metabolism in the liver. Several bone studies have utilized tocotrienol combined with a nanocarrier to produce a controlled release of tocotrienol particles into the system. However, the potential of delivering tocotrienol–nanocarrier combination through the intraosseous route has never been explored. In this study, tocotrienol was combined with a nanocarrier, poly lactic-co-glycolic acid (PLGA), and injected intraosseously into the bones of ovariectomized rats to produce targeted and controlled delivery of tocotrienol into the bone microenvironment. This new form of tocotrienol delivery was compared with the conventional oral delivery in terms of their effects on bone parameters. Forty Sprague–Dawley rats were divided into five groups. The first group was sham operated, while other groups were ovariectomized (OVX). Following 2 months, the right tibiae of all the rats were drilled at the metaphysis region to provide access for intraosseous injection. The estrogen group (OVX + ESTO) and tocotrienol group (OVX + TTO) were given daily oral gavages of Premarin (64.5 mg/kg) and annatto-tocotrienol (60 mg/kg), respectively. The locally administered tocotrienol group (OVX + TTL) was given a single intraosseous injection of tocotrienol–PLGA combination. After 8 weeks of treatment, both OVX + TTO and OVX + TTL groups have significantly lower bone markers and higher bone mineral content than the OVX group. In terms of bone microarchitecture, both groups demonstrated significantly higher trabecular separation and connectivity density than the OVX group (p < 0.05). Both groups also showed improvement in bone strength by the significantly higher stress, strain, stiffness, and Young’s modulus parameters. In conclusion, daily oral tocotrienol and one-time intraosseous injection of tocotrienol–PLGA combination were equally effective in offering protection against ovariectomy-induced bone changes.
format	article
author	Nurul ‘Izzah Ibrahim Hasnul ‘Iffah Mohd Noor Ahmad Naqib Shuid Sharlina Mohamad Mohd Maaruf Abdul Malik Putri Ayu Jayusman Ahmad Nazrun Shuid Isa Naina Mohamed
author_facet	Nurul ‘Izzah Ibrahim Hasnul ‘Iffah Mohd Noor Ahmad Naqib Shuid Sharlina Mohamad Mohd Maaruf Abdul Malik Putri Ayu Jayusman Ahmad Nazrun Shuid Isa Naina Mohamed
author_sort	Nurul ‘Izzah Ibrahim
title	Osteoprotective Effects in Postmenopausal Osteoporosis Rat Model: Oral Tocotrienol vs. Intraosseous Injection of Tocotrienol-Poly Lactic-Co-Glycolic Acid Combination
title_short	Osteoprotective Effects in Postmenopausal Osteoporosis Rat Model: Oral Tocotrienol vs. Intraosseous Injection of Tocotrienol-Poly Lactic-Co-Glycolic Acid Combination
title_full	Osteoprotective Effects in Postmenopausal Osteoporosis Rat Model: Oral Tocotrienol vs. Intraosseous Injection of Tocotrienol-Poly Lactic-Co-Glycolic Acid Combination
title_fullStr	Osteoprotective Effects in Postmenopausal Osteoporosis Rat Model: Oral Tocotrienol vs. Intraosseous Injection of Tocotrienol-Poly Lactic-Co-Glycolic Acid Combination
title_full_unstemmed	Osteoprotective Effects in Postmenopausal Osteoporosis Rat Model: Oral Tocotrienol vs. Intraosseous Injection of Tocotrienol-Poly Lactic-Co-Glycolic Acid Combination
title_sort	osteoprotective effects in postmenopausal osteoporosis rat model: oral tocotrienol vs. intraosseous injection of tocotrienol-poly lactic-co-glycolic acid combination
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/1430ba1163d045ebb27966a6258456e1
work_keys_str_mv	AT nurulizzahibrahim osteoprotectiveeffectsinpostmenopausalosteoporosisratmodeloraltocotrienolvsintraosseousinjectionoftocotrienolpolylacticcoglycolicacidcombination AT hasnuliffahmohdnoor osteoprotectiveeffectsinpostmenopausalosteoporosisratmodeloraltocotrienolvsintraosseousinjectionoftocotrienolpolylacticcoglycolicacidcombination AT ahmadnaqibshuid osteoprotectiveeffectsinpostmenopausalosteoporosisratmodeloraltocotrienolvsintraosseousinjectionoftocotrienolpolylacticcoglycolicacidcombination AT sharlinamohamad osteoprotectiveeffectsinpostmenopausalosteoporosisratmodeloraltocotrienolvsintraosseousinjectionoftocotrienolpolylacticcoglycolicacidcombination AT mohdmaarufabdulmalik osteoprotectiveeffectsinpostmenopausalosteoporosisratmodeloraltocotrienolvsintraosseousinjectionoftocotrienolpolylacticcoglycolicacidcombination AT putriayujayusman osteoprotectiveeffectsinpostmenopausalosteoporosisratmodeloraltocotrienolvsintraosseousinjectionoftocotrienolpolylacticcoglycolicacidcombination AT ahmadnazrunshuid osteoprotectiveeffectsinpostmenopausalosteoporosisratmodeloraltocotrienolvsintraosseousinjectionoftocotrienolpolylacticcoglycolicacidcombination AT isanainamohamed osteoprotectiveeffectsinpostmenopausalosteoporosisratmodeloraltocotrienolvsintraosseousinjectionoftocotrienolpolylacticcoglycolicacidcombination
_version_	1718422807210098688

Osteoprotective Effects in Postmenopausal Osteoporosis Rat Model: Oral Tocotrienol vs. Intraosseous Injection of Tocotrienol-Poly Lactic-Co-Glycolic Acid Combination

Ejemplares similares