Antioxidative and anti-inflamatory effectiveness of flavonoids in retinoic acid induced osteoporosis in rat

Nemrava, Johann (2016) Antioxidative and anti-inflamatory effectiveness of flavonoids in retinoic acid induced osteoporosis in rat. Doctoral thesis, Faculty of Science > Department of Biology.

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Abstract

Osteoporosis is a skeletal disease characterized by decreased bone mineral density (BMD) and bone microarchitecture disorder. The risk of osteoporosis can be genetic or acquired. Numerous medications including 13-cis retinoic acid (13cRA) contribute to the acquired risk. In this PhD thesis it has been proved that 13cRA at a dose of 80 mg kg-1 during 14 days successfully causes osteoporotic changes in the rats through the mechanisms of increased oxidative stress (OS) and the formation of reactive radicals, reduced activity of osteoblasts and increased osteoclast activity, decreased estrogen levels and the appearance of inflammatory cytokines which activate osteoclasts and cause osteoblasts apoptosis, reduction in vitamin D receptor activity, decreased absorption of Ca2+ in the intestine, increase the Ca secretion by kidneys and the effects on the parathyroid hormone. Through the model of osteoporosis caused by 13cRA (RMO) in this study are shown antioxidative, anti-inflammatory, phytoestrogenic and regenerative features of flavonoids (chrysin, proanthocyanidins, naringenin, icariin and quercetin) on osteoblasts and osteoclasts inhibition, which has been shown by the relationships between markers of OS, biochemical markers of bone turnover, measurements of bone mass and geometric determinants of thigh bones, measurements of proinflammatory cytokines and histopathological bone damage. The effects of flavonoids are compared through these features with alendronate, nowadays the medication of choice to treat osteoporosis, and the evaluation of DNA damage at RMO rats after the treatment with flavonoids and alendronate is presented. The results show the possibility of a new pharmacological approach for the treatment of osteoporotic changes, where easy accessibility, cost-effectiveness and lack of toxicity may be an advantage in the application of flavonoids with respect to alendronate. Furthermore, this study contributes to a better understanding of the relationship between diet and health and development of the concept of functional foods with the fundamental aim of achieving better health status, prevention and treatment of disease.

Item Type: Thesis (Doctoral thesis)
Keywords: Osteoporosis, 13-cis retinoic acid (13cRA), oxidative stress (OS), reactive radicals, inflammatory cytokines, osteoblasts and osteoclasts, flavonoids
Supervisor: Oršolić, Nada
Date: 2016
Number of Pages: 255
Subjects: NATURAL SCIENCES > Biology
Divisions: Faculty of Science > Department of Biology
Depositing User: Grozdana Sirotic
Date Deposited: 11 Jan 2017 11:21
Last Modified: 11 Jan 2017 11:21
URI: http://digre.pmf.unizg.hr/id/eprint/5396

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