Abstract

Oxidative stress (OS) mediators, together with the inflammatory processes, are considered as threatening factors for bone health. The aim of this study was to investigate effects of flavonoids naringenin and chrysin on OS, inflammation, and bone degradation in retinoic acid (13cRA)-induced secondary osteoporosis (OP) in rats. We analysed changes in body and uterine weight, biochemical bone parameters (bone mineral density (BMD), bone mineral content (BMC), markers of bone turnover), bone geometry parameters, bone histology, OS parameters, biochemical and haematological parameters, and levels of inflammatory cytokines. Osteoporotic rats had reduced bone Ca and P levels, BMD, BMC, and expression of markers of bone turnover, and increased values of serum enzymes alkaline phosphatase (ALP) and lactate dehydrogenase (LDH). Malondialdehyde (MDA) production in liver, kidney, and ovary was increased, while the glutathione (GSH) content and activities of antioxidant enzymes were reduced and accompanied with the enhanced release of inflammatory mediators TNF-α, IL-1β, IL-6, and RANTES chemokine (regulated on activation normal T cell expressed and secreted) in serum. Treatment with chrysin or naringenin improved bone quality, reduced bone resorption, and bone mineral deposition, although with a lower efficacy compared with alendronate. However, flavonoids exhibited more pronounced antioxidative, anti-inflammatory and phytoestrogenic activities, indicating their great potential in attenuating bone loss and prevention of OP.

Highlights

  • Osteoporosis (OP) is a systemic skeletal disease characterized by reduced bone mass, bone weakness, and enhanced bone fragility

  • After 14 days, osteoporosis was successfully induced with 13cRA suspension in the rat model; the values of bone mineral density (BMD) in the proximal and distal metaphysis of the femoral neck were significantly lower in 13cRA group than in the control group (BMD proximal: 0.242 ± 0.005 vs. 0.279 ± 0.013 (p < 0.05); BMD distal: 0.240 ± 0.002 vs. 0.282 ± 0.012 (p < 0.05))

  • After 2 weeks of 13cRA administration, a slight weight loss was observed compared with the control group; the changes in body weight (BW) in the 13cRA group on day 6 and 12 were 3.58% and 7.74%, respectively, whereas in healthy control rats the BW increased by 5.10% and 11.66%, respectively

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Summary

Introduction

Osteoporosis (OP) is a systemic skeletal disease characterized by reduced bone mass, bone weakness, and enhanced bone fragility. There are two major categories of OP. Primary OP is the most common form, and includes postmenopausal and senile OP. It is associated with the ageing- and hormone-depletion-related gradual bone loss, and results in microarchitectural alterations of bone tissue, low bone density, and increased fracture susceptibility [1]. Secondary OP is caused by specific clinical conditions and medications. It may arise from hormonal imbalance, nutritional disorders, free radicals, cytokines, diseases (such as renal disease and cancers), or due to adverse effects of drug therapy [2–8]

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