Melatonin supports alendronate in preserving bone matrix and prevents gastric inflammation in ovariectomized rats

Esra Bihter Gürler, Özlem Tuğçe Çilingir-Kaya, Irem Peker Eyüboglu, Feriha Ercan, Mustafa Akkiprik, Russel J Reiter, Berrak Yegen

Research output: Contribution to journalArticle

Abstract

The anti-catabolic bisphosphonate alendronate is considered as the first-line medical treatment in post-menopausal osteoporosis; but several side effects, including gastric mucosal injury, are associated with its use. The aim was to elucidate whether combined treatment with melatonin plus alendronate would be more advantageous in the maintenance of bone and the prevention of gastric side effects. Under anaesthesia, female Sprague-Dawley rats underwent bilateral ovariectomy (OVX), while control group had sham surgery. Four weeks after the surgery, OVX rats were treated with saline, melatonin (25 μg/mL/d), alendronate (70 μg/kg/wk), melatonin + alendronate, melatonin + melatonin receptor antagonist (luzindole, 10 μg/kg/d) or alendronate + melatonin + luzindole for 8 weeks. Rats were euthanized at the end of 12th week. Runx2 expression, apoptotic cells, and trabecular thickness were evaluated in tibiae, while gastric tissues were analysed for oxidative injury parameters. In all OVX groups, Runx2 expression was depressed. Saline-treated OVX group presented an extreme decrease in calcified area in opposition to melatonin- or alendronate-treated groups, while the bones in alendronate + melatonin-treated group were similar to those of the sham-operated group. Concomitant with the improvements examined histologically in bone tissues, quantitative TUNEL (+) cells were similarly lower in alendronate- or melatonin-treated groups. Oxidative gastric damage was increased in saline- or alendronate-treated groups, which were depressed in the presence of melatonin. Although melatonin and alendronate exerted similar supportive effects on the maintenance of bone mass, melatonin may have a more advantageous impact by protecting against OVX-induced gastric injury, which was aggravated by alendronate use. Highlights: Our results demonstrate that alendronate and melatonin had similar supportive effects on the maintenance of bone mass, while melatonin prevented the gastric side effects of alendronate, making this combination an advisable therapeutic approach in the treatment of menopausal osteoporosis.

Original languageEnglish (US)
JournalCell Biochemistry and Function
DOIs
StatePublished - Jan 1 2019

Fingerprint

Alendronate
Bone Matrix
Melatonin
Rats
Stomach
Bone
Inflammation
Bone and Bones
Maintenance
Surgery
Wounds and Injuries
Melatonin Receptors
Tissue
Postmenopausal Osteoporosis
In Situ Nick-End Labeling
Diphosphonates
Ovariectomy
Tibia
Osteoporosis
Sprague Dawley Rats

Keywords

  • alendronate
  • gastric injury
  • melatonin
  • osteoporosis
  • post-menopausal

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Cell Biology

Cite this

Melatonin supports alendronate in preserving bone matrix and prevents gastric inflammation in ovariectomized rats. / Gürler, Esra Bihter; Çilingir-Kaya, Özlem Tuğçe; Peker Eyüboglu, Irem; Ercan, Feriha; Akkiprik, Mustafa; Reiter, Russel J; Yegen, Berrak.

In: Cell Biochemistry and Function, 01.01.2019.

Research output: Contribution to journalArticle

Gürler, Esra Bihter ; Çilingir-Kaya, Özlem Tuğçe ; Peker Eyüboglu, Irem ; Ercan, Feriha ; Akkiprik, Mustafa ; Reiter, Russel J ; Yegen, Berrak. / Melatonin supports alendronate in preserving bone matrix and prevents gastric inflammation in ovariectomized rats. In: Cell Biochemistry and Function. 2019.
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AU - Çilingir-Kaya, Özlem Tuğçe

AU - Peker Eyüboglu, Irem

AU - Ercan, Feriha

AU - Akkiprik, Mustafa

AU - Reiter, Russel J

AU - Yegen, Berrak

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