Sains Malaysiana 42(11)(2013): 1591–1597

 

Membandingkan Kesan antara Fraksi-kaya Tokotrienol, Kalsium dan Estrogen Terhadap Metabolisme Tulang Tikus Terovariektomi

(Comparing the Effects of Tocotrienol-rich Fraction, Calcium and Estrogen

on Bone Metabolism in Ovariectomized Rats)

 

Norliza Muhammad*, Surayya Razali, Ahmad Nazrun Shuid, Norazlina Mohamed

& Ima Nirwana Soelaiman

Jabatan Farmakologi, Fakulti Perubatan Universiti Kebangsaan Malaysia

Jalan Raja Muda Abdul Aziz, 50300 Kuala Lumpur, Malaysia

 

Diserahkan: 27 Oktober 2011/Diterima: 19 April 2013

 

ABSTRAK

Beberapa kajian sebelum ini menunjukkan penglibatan pengaruh tekanan pengoksidaan dalam patogenesis osteoporosis. Justeru agen antioksida berpotensi untuk digunakan bagi merawat dan mencegah osteoporosis. Dalam kajian ini, vitamin E sawit dalam bentuk fraksi-kaya tokotrienol ('tocotrienol-rich fraction', TRF) telah digunakan. Perbandingan dibuat antara rawatan TRF, kalsium dan estrogen terhadap parameter histomorfometri struktur tulang, kandungan kalsium dan kekuatan biomekanikal tulang pada tikus betina terovariektomi. Sebanyak 48 ekor tikus betina Sprague-Dawley dibahagikan kepada enam kumpulan, iaitu kawalan asas, sham, ovariektomi (OVX) dan kumpulan ovariektomi yang diberi rawatan samada kalsium, estrogen atau TRF. Rawatan diberikan secara paksaan oral selama dua bulan. Berdasarkan ujian histomorfometri tulang, tikus-tikus terovariektomi yang diberi kalsium, estrogen atau TRF menunjukkan peningkatan isi padu trabekular dan pengurangan jarak antara tulang trabekular secara signifikan berbanding dengan tikus kawalan ovariektomi. Disamping itu, rawatan estrogen dan TRF meningkatkan ketebalan trabekular secara signifikan berbanding dengan kumpulan OVX dan kalsium. Melalui ujian kandungan kalsium tulang, tikus yang diberi rawatan kalsium mempunyai aras kandungan kalsium dalam vertebra lumbar ke-empat yang lebih tinggi berbanding dengan kumpulan sham dan OVX. Kesimpulannya, rawatan kalsium, estrogen dan TRF berupaya memberikan kesan positif terhadap struktur tulang trabekular. TRF dan estrogen mampu mencegah penipisan tulang. Rawatan kalsium meningkatkan kandungan kalsium tulang, namun ia tidak berupaya untuk mencegah penipisan tulang.

 

Kata kunci: Estrogen; histomorfometri struktur tulang; mineral tulang; osteoporosis; tokotrienol; vitamin E

 

ABSTRACT

Previous studies showed the role of oxidative stress in the pathogenesis of osteoporosis. Thus antioxidant agents have the potential to be used in the treatment and prevention of osteoporosis. In this study, vitamin E in the form of tocotrienol-rich fraction (TRF) was used. Comparison of the effects of treatments was made among TRF, calcium and estrogen. A total of 48 female Sprague-Dawley rats were divided into six groups: baseline, sham-operated, ovariectomized control and ovariectomized given calcium, estrogen or TRF. The treatment agents were administered via oral gavage for two months. Bone histomorphometry showed that treatment with either calcium, estrogen or tocotrienol was able to increase the trabecular volume and reduce the distance between the trabecular bone significantly compared with the ovariectomy control group. Treatment with either estrogen or tocotrienol showed significant increase in the thickness of the trabecular compared with the control group. Based on the calcium content test, supplementation with calcium increased the levels of calcium content in the fourth vertebral lumbar significantly compared with the sham and ovariectomy group. In conclusion, calcium, estrogen and tocotrienol had positive effects on the trabecular bone. However, tocotrienol was more superior to calcium or estrogen in preventing bone loss in postmenopausal osteoporosis. Tocotrienol prevented bone thinning and loss of volume without the side effects as estrogen. Although calcium can improve the bone calcium content, still, it was unable to prevent bone thinning.

 

Keywords: Bone mineral content; estrogen; osteoporosis; structural histomorphometry; tocotrienol; vitamin E

RUJUKAN

Ahmad, N.S., Khalid, B.A.K., Luke, D.A. & Ima-Nirwana, S. 2005. Tocotrienol offers better protection than tocopherol from free radical induced damage on rat bone. Clinical & Experimental Pharmacology & Physioliology 32: 761-770.

Ahmad, N.S., Zulfadli, M., Norazlina, M., Norliza, M.& Ima Nirwana, S. 2010. Vitamin E exhibits bone anabolic actions in normal male rats. Journal of Bone and Mineral Metabolism 28(2): 149-156.

Ainslie, D.A., Morris, M.J., Wittert, G., Turnbull, H., Proietto, J. & Thorburn, A.W. 2001. Estrogen deficiency causes central leptin insensitivity and increased hypothalamic neuropeptide Y. International Journal of Obesity and Related Metabolic Disorders 25: 1680-1688.

Amir, Q., Snow, V., Shekelle, P., Hopkins, R., Forciea, M.A. & Owens, D.K. 2008. Pharmacologic treatment of low bone density or osteoporosis to prevent fractures: A clinical practice guideline from the American College of Physicians. Annals of Internal Medicine 149: 404-415.

Bagi, C.M., Wilkie, D., Georgelos, K., Williams, D. & Bertolini, D. 1997. Morphological and structural characteristics of the proximal femur in human and rat. International Bone and Mineral Society 21(3): 261-267.

Casanueva, F.F. & Dieguez, C. 1999. Neuroendocrine regulation and actions of leptin. Front. Neuroendocrinology 20: 317- 363.

Draper, C.R., Dick, I.M. & Prince, R.L. 1999. The effect of estrogen deficiency on calcium balance in mature rats. Calcified Tissue International 64: 325-328.

Fathilah, S.N., Ahmad, N.S., Norazlina, M., Norliza, M. & Ima Nirwana, S. 2012. Labisia pumila protects the bone of estrogen-deficient rat model: A histomorphometric study. Journal of Ethnopharmacology 142(1): 294-299.

Gal-Moscovici, A.M. & Popovtzer, M.M. 2005. Treatment of osteoporotic ovariectomized rats with 24, 25(OH)2D3. European Journal of Clinical Investigation 35: 375-379.

Hapidin, H., Othman, F., Soelaiman, I.N., Shuid, A.N. & Luke, D.A. 2007. Negative effects of nicotine on bone-resorbing cytokines and bone histomorphometric parameters in male rats. Journal of Bone & Mineral Metabolism 25: 93-98.

Hazenberg, J.G., Taylor, D. & Lee, T.C. 2007. The role of osteocytes and bone microstructure in preventing osteoporotic fractures. Osteoporosis International 18: 1-8.

Henderson, B.E., Ross, R. & Bernstein, L. 1988. Estrogens as a cause of human cancer. The Richard and Hinda Rosenthal Cancer Research 48: 246-253.

Ima-Nirwana, S. & Fakhrurazi, H. 2002. Palm vitamin E protects bone against dexamethasone-induced osteoporosis in male rats. Medical Journal of Malaysia 57(2): 133-141.

Kessenich, C.R. 2007. Calcium and vitamin D supplementation for postmenopausal bone health. The Journal for Nurse Practitioners 3(3): 155-159.

Kolios, L., Hoerster, A.K., Sehmisch, S., Malcherek, M.C., Rack, T., Tezval, M., Seidlova-Wuttke, D., Wuttke, W., Stuermer, K.M. & Stuermer, E.K. 2009. Do estrogen and alendronate improve metaphyseal fracture healing when applied as osteoporosis prophylaxis? Calcified Tissue International 86(1): 23-32.

Li, X., Ominsky, M.S., Warmington, K.S., Morony, S., Gong, J., Cao, J., Gao, Y., Shalhoub, V., Tipton, B., Haldankar, R., Chen, Q., Winters, A., Boone, T., Geng, Z., Niu, Q.T., Ke, H.Z., Kostenuik, P.J., Simonet, W.S., Lacey, D.L. & Paszty, C. 2009. Sclerostin antibody treatment increases bone formation, bone mass, and bone strength in a rat model of postmenopausal osteoporosis. Journal of Bone & Mineral Research 24: 578-588.

Morris, H.A., O’Loughlin, P.D., Mason, R.A. & Schulz, S.R. 1995. The effect of oophorectomy on calcium homeostasis. Bone 17(4): 169S-174S.

Nancy, E.L. 2005. Epidemiology, etiology, and diagnosis of osteoporosis. American Journal of Obstetrics & Gynecology 194(2): S3-S11.

Norazlina, M., Soelaiman, I., Mohd, T.A.G. & Khalid, B.A.K. 2002. Tocotrienols are needed for normal bone calcification in growing female rats. Asia Pacific Journal of Clinical Nutrition 11(3): 194-199.

Osakada, F., Hashino, A. & Kume, T. 2003. Neuroprotective effects of α-tocopherol on oxidative stress in rat striatal cultures. European Journal of Pharmacology 465: 15-22.

Parfit, A.M., Drezner, M.K., Glorieux, F.H., Kanis, J.A., Malluche, H., Meuner, P.J., Ott, S.M. & Recker, R.R. 1987. Bone histomorphometry: Standardization of nomenclature, symbols and units. Journal of Bone & Mineral Research 6: 595-610.

Reid, I.R., Ames, R.W., Evans, M.C., Gamble, G.D. & Sharpe, S.J. 1995. Long-term effects of calcium supplementation on bone loss and fractures in postmenopausal women: A randomized controlled trial. American Journal of Medicine 98: 331-335.

Sheehan, D. & Hrapchak, B. 1980. Theory and Practice of Histotechnology. Ed. Ke-2. Elsevier Health Sciences New York. Hlmn. 226-227.

Shinoda, M., Latour, M.G. & Lavoie, J.M. 2002. Effects of physical training on body composition and organ weights in ovariectomized and hyperestrogenic rats. International Journal of Obesity 26: 335-343.

Steven, T.H., Leder, B. & Pinkerton, J. 2010. Breast cancer and bone loss. The Journal of Clinical Endocrinology & Metabolism 95(70): 212-220.

Torto, R., Boghossian, S., Dube, M.G., Kalra, P.S & Kalra, S.P. 2006. Central leptin gene therapy blocks ovariectomy-induced adiposity. Obesity 14: 1312-1319.

 

 

*Pengarang untuk surat-menyurat; email: norliza_ssp@yahoo. com

 

 

 

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