학술논문
Protuoksidativna i protuupalna učinkovitost flavonoida u osteoporozi izazvanoj retinoičnom kiselinom u štakoraAntioxidative and anti-inflamatory effectiveness of flavonoids in retinoic acid induced osteoporosis in rat
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TEXT
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Source
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Language
Croatian
Abstract
Osteoporoza je bolest kostura karakterizirana smanjenjem koštane mineralne gustoće (BMD) i poremećajem mikroarhitekture koštanog tkiva. Rizik za osteoporozu može biti genetski ili stečeni. Stečenom riziku pridonose brojni lijekovi, uključujući 13-cis retinoičnu kiselinu (13cRA). U ovome radu dokazano je da 13cRA u dozi od 80 mg kg-1 tijekom 14 dana uspješno uzrokuje osteoporotske promjene u štakora putem mehanizama povećanog oksidativnog stresa (OS) i stvaranja reaktivnih radikala, smanjenja aktivnosti osteoblasta i povećanja aktivnosti osteoklasta, smanjenja razine estrogena i pojavnosti upalnih citokina koji aktiviraju osteoklaste i uzrokuju apoptozu osteoblasta, smanjenja aktivnosti receptora vitamina D, smanjenja apsorpcije Ca2+ u crijevima i povećanja izlučivanja Ca bubrezima i učincima na paratireoidni hormon. Kroz model osteoporoze prouzročen 13cRA (RMO) u ovom istraživanju prikazana su protuoksidativnna, protuupalna, fitoestrogenska i regenerativna svojstva flavonoida (krizina, proantocijanida, naringenina, ikarina i kvercetina ) na osteoblaste i inhibiciju osteoklasta, što je pokazano odnosima između biljega OS, biokemijskim biljezima koštanog preokreta, mjerenjima koštane mase i geometrijskih odrednica bedrenih kosti, mjerenjima proupalnih citokina i histopatoloških oštećenja kosti. Učinci flavonoida uspoređeni su kroz navedene odrednice sa alendronatom, danas lijekom izbora u liječenju osteoporoze, a prikazana je i procjena oštećenja DNA kod RMO štakora nakon obrade flavonoidima i alendronatom. Dobiveni rezultati pokazuju mogućnost novog farmakoterapijskog pristupa u terapiji osteoporotičnih promjena u kojem laka dostupnost, ekonomska isplativost i nedostatak toksičnosti mogu biti prednost u primjeni flavonoida u odnosu na alendronat. Nadalje ovo istraživanje pridonosi boljem razumijevanju odnosa između prehrane i zdravlja te razvoja koncepta funkcionalne hrane s temeljnim ciljem postizanja boljeg zdravstvenog statusa, spriječavanja i liječenja bolesti.
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.
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.