Long term glucocorticoids administration induces oxidative stress which leads to alteration of bone structure and strength. Palm oil is rich in tocotrienol, an antioxidant. It can be used for the prevention of oxidative stress related diseases. The main objective of this study was to determine the mechanism of palm tocotrienol in maintaining the bone structure and strength in glucocorticoidinduced osteoporosis. Thirty two adult male Sprague-Dawley rats, aged 3 months, weighing 300-320 g rats were used in this study. Sixteen rats undergone adrenalectomy and were administered with 120μg/kg/day intramuscular injection of dexamethasone. Eight rats were supplemented with oral palm tocotrienol 60 mg/kg/day (Adrx+Dex+PTT) and the other eight rats were given oral vehicle palm olein 0.1 ml/kg/day (Adrx+Dex). Eight rats underwent sham procedure and were given vehicle palm olein 0.05 ml/kg/day by intramuscularly and oral 0.1 ml/kg/day (Sham). The rats were euthanized after two months of treatments. Eight rats were euthanized after acclimatic action without receiving any treatment (Baseline). The right femurs were used for bone biomechanical strength and histomorphometry analysis while the left for gene expression and oxidative stress enzymes activities. The results indicated that long-term glucocorticoid treatment significantly increased bone resorption marker, CTX (6060.7 ± 410 pg/ml) and decreased bone structure and strength. Osteoblast and osteoclast related genes expressions indicated an increase in bone turnover. Supplementation of palm tocotrienol had maintained serum resorption (2619.4 + 209 pg/ml) marker level and preserved bone structure and strength. Gene expression analysis showed decrease in bone resorption. The findings suggested that palm tocotrienol has potential benefits against glucocorticoid-induced osteoporosis by regulating osteoblast and osteoclast related gene expressions.
Protective Effects of Palm Tocotrienol Against Glucocorticoid Induced Osteoporosis via Regulation of Gene Expressions
Abstrak
Pengambilan glukokortikoid jangka panjang mengaruh stres oksidatif yang mengakibatkan perubahan struktur dan kekuatan tulang. Minyak sawit kaya dengan tokotrienol yang merupakan sejenis antioksidan. Ia boleh digunakan bagi mencegah penyakit yang berkaitan dengan stres oksidatif. Kajian ini bertujuan untuk menentukan mekanisme kesan perlindungan tokotrienol sawit terhadap osteoporosis aruhan glukokortikoid. Sebanyak 32 ekor tikus Sprague-Dawley jantan telah digunakan bagi kajian ini. 16 ekor telah menjalani adrenalektomi dan diberi suntikan deksametason 120μg/kg/hari secara intramukular. Sebanyak lapan ekor tikus diberi suplementasi tokotrienol sawit 60 mg/kg/hari manakala 8 ekor lagi diberi makan vehikel minyak sawit olein 0.1 ml/kg/hari secara gavaj oral. Lapan ekor tikus menjalani pembedahan sham dan diberi vehikel minyak sawit olein 0.05 ml/kg/hari melalui suntikan intramuskular diberi makan vehikel minyak sawit olein 0.1 ml/kg/hari secara gavaj oral. Lapan ekor tikus dijadikan kumpulan kawalan asas yang dikorbankan tanpa diberikan apa-apa rawatan. Tikus-tikus tersebut dikorbankan selepas dua bulan menerima rawatan. Tulang femur kanan digunakan untuk menganalisa kekuatan biomekanikal dan histomorfometri tulang, manakala tulang femur kiri digunakan untuk menganalisa ekspresi gengen dan aktiviti enzim-enzim stress oksidatif. Hasil kajian menunjukkan rawatan glukokortikoid jangka panjang telah secara signifikan meningkatkan petanda resorpsi dan mengurangkan kekuatan dan struktur tulang. Ekspresi gen-gen yang berkaitan dengan osteoblast dan osteoklas menunjukkan peningkatan kadar tukar ganti tulang. Suplementasi tokotrienol sawit telah dapat mengekalkan petanda serap semula tulang dan memelihara struktur dan kekuatan tulang. Ekspresi gengen juga telah menunjukkan pengurangan kadar tukar ganti tulang. Melalui hasil kajian ini dapat disimpulkan bahawa tokotrienol sawit berpotensi digunakan sebagai rawatan profilaksis terhadap osteoporosis aruhan glukokortikoid melalui mekanisme pengawal seliaan ekspresi gen-gen yang berkaitan dengan osteoblas dan osteoklas.
Kata kunci
Abstract
Keywords
|
|
