IJAR.2020.204
Type of Article: Original Research
Volume 8; Issue 3.3 (September 2020)
Page No.: 7728-7737
DOI: https://dx.doi.org/10.16965/ijar.2020.204
PROMISING EFFECT OF DAPAGLIFLOZIN ON OVARIECTOMIZED RAT MODEL OF OSTEOPOROSIS
Amany Ali Nawar 1, Nancy Mohamed El Sekily *2.
1 Clinical pharmacology Department, Faculty of Medicine, Alexandria University, Egypt.
*2 Anatomy and Embryology Department, Faculty of Medicine, Alexandria University, Egypt.
Corresponding author: Nancy Mohamed Aly El-Sekily, Anatomy and Embryology, Department, Faculty of Medicine, Alexandria University, Egypt. +0201222359100 E-Mail: nancyelsekily@yahoo.com
ABSTRACT
Introduction: Osteoporosis makes bones become frail thus fragile, that a fall or even gentle burdens prompting a crack. Several studies had documented that osteoporosis incidence is increased much more in diabetic patient. Dapagliflozin, is used in Type 2 diabetes management, as a selective inhibitor of sodium/glucose cotransporter-2 (SGLT2). Few study tackled the impact of dapagliflozin on bone metabolism. In this study we aim to determine the impact of dapagliflozin on a rat model of osteoporosis.
Materials and methods: Thirty adult female Wistar albino rats were used in this experiment. They were equally divided into three groups. Group I sham-operated control, group II ovariectomized (OVX), and group III ovariectomized (OVX) treated with dapagliflozin (DAPA) 10 mg/kg/day orally for 8 weeks. After 8weeks, plasma levels of calcium (Ca+2), phosphorous (P), alkaline phosphatase (ALP), Tartrate-Resistant Acid Phosphatase 5b (TRAP 5b), tumor necrosis factor-α (TNF-α), serum osteocalcin level, serum osteoprotegerin level, AMP-activated protein kinase (AMPK) and advanced glycosylation end products (AGEs) were analysed. The distal end of femur bones were excised for histological and morphometric studies.
Results: In the current study, the biochemical results of ovariectomized (OVX) rat group showed increase in serum level of phosphorus, alkaline phosphatase, Tartrate-Resistant Acid Phosphatase 5b (TRAP 5b), osteocalcin, advanced glycosylation end products (AGEs) and tumor necrosis factor-α (TNF-α) . While the serum level of calcium, osteoprotegrin and AMP-activated protein kinase (AMPK) was decreased. The biochemical results of (OVX) group treated with DAPA showed a significant change in serum level of calcium, alkaline phosphatase, TRAP 5b, osteocalcin, osteoprotegrin and AMPK. While the serum level of phosphorus, AGEs and TNF- α showed non significant change in the same group. In the present study, the (OVX) rat group showed features of osteoporosis at the epiphyseal plate of femur. These features were focal areas of disrupted arrangement of the layers of chondrocytes, some areas of the matrix appeared pale, the bone trabeculae were thinner than normal, multiple resorption cavities and some areas of hypocellularity. After oral administration of dapagliflozin to the OVX rats for eight weeks, the osteoporotic findings in femur by H&E showed improvement. The chondrocytes appeared almost normally organized and the bone trabeculae were of normal thickness. By morphometric assessment, the thickness of bone trabeculae of OVX treated with DAPA group (69.9±15.6) increased in comparaison to the OVX group (61.0± 18.2).
Conclusion: Dapaglaflozin has an antiosteoporotic effect in ovariectomy induced osteoporosis in rat.
KEY WORDS: Dapagliflozin, Osteoporosis, bilateral ovaricteomy.
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