Suplemen Calcitriol Dosis Tinggi Mencegah Osteoporosis dan Memicu Urolitiasis pada Tikus Ovariektomi

https://doi.org/10.22146/jsv.47032

hartiningsih hartiningsih(1*), devita anggraeni(2)

(1) Fakultas Kedokteran Hewan, Universitas Gadjah Mada
(2) Fakultas Kedokteran Hewan, UGM
(*) Corresponding Author

Abstract


Calcitriol supplementation in ovariectomized rats for 8 weeks reduce osteoporosis risk and safe for kidney depend a proper dose. The objective of the research was to study the efectivity of high dose calcitriol for osteoporosis prevention and safe for kidney  in ovariectomized Wistar rats. Fifteen female Wistar rats at 8 weeks of age were randomly divided into three  groups of five which were sham operated rats (KN), ovariectomized rats (KOV), and ovariectomized rats+calcitriol supplementation 200ng/day (OVD200). After 8 weeks of treatment, blood samples were taken from plexus orbitalis medialis for estrogen analysis. All rats were then euthanized, left tibia and left kidney were taken for histopathological examination using hematoxylin and eosin stain. Immunohistochemistry using anti TRAP5b monoclonal antibody was also done for left tibia by streptavidin-biotin.  The results showed that estradiol level of KOV was significantly decreased compared with KN (P<0.05), meanwhile, estradiol levels of OVD200 were not significantly different compared with KOV. Histopathologic figure of kidney in KOV was not different compared with KN. Glomerulus was surrounded by Bowman‘s capsule, proximal and distal convoluted tubulus were lined with typical cuboidal epithelium. Immunohistochemistry result of proximal tibial epiphysis in KOV were shown more tartrate resistant alkaline phosphatase 5b (TRAP5b) expression in trabecular bone, which was located in bone marrow space, and trabecular speculum surface as well. Meanwhile, proximal tibia epiphysis in OVD200 had less tartrate resistant alkaline phosphatase 5b (TRAP5b) expression compared with KOV. Histopathologic figure  of proximal tibia epiphysis in group OVD200 was shown more trabecular bone speculum and less adipocyte in the bone marrow compared with KOV. Histopathologic figure of kidney in OVD200 was showed glomerular  hypertrophy and atrophy, as well as protein deposits in proximal convoluted tubules epithelium.  In conclusion, calcitriol supplementation 200ng/day in ovariectomized rats for 8 weeks prevented osteoporosis risk but trigger urolithiasis.

 

Key words :  : Calcitriol, osteoporosis, ovariectomized rats, urolithiasis


Keywords


Calcitriol; osteoporosis; ovariectomized rats; urolithiasis

Full Text:

PDF


References

Akil et al., (2006) Akil I, Kavukcu S, Inan S, Yilmaz O, Atilla P, Islekel H, Nese N, and Muftuoglu S. 2006. Evaluation of histologic changes in the urinary tract of hypercalciuric rats. Pediatr Nephrol 21: 1681-1689.

Alatalo SL, Halleen JM, Hentunen TA, Monkkonen J, Vaananen HK. 2000. Rapid screening method for osteoclast differentiation in vitro that measures tartrate-resistant acid phosphatase 5b activity secreted into the culture medium. Clin Chem 46: 1751–4.

Anderson, G.L., Chlebowski R.T., Rossouw J.E. (2006) Prior hormone therapy and breast cancer risk in the women’s health initiative randomized trial of estrogen plus progestin. Maturutas, 55:.103-115.

Bartges JW, 2011. Urinary saturation testing In: Bartges J, Polzin DJ, eds. Nephrology and urology of small animals. Ames: Wiley-Blackwell pp 75-85.

Bischoff-Ferrari, H.A., Willett, W.C., Wong, J.B., Giovannucci, E., Dietrich, T., Dawson-Hughes, B. (2005) Fracture prevention with vitamin D supplementation: a meta-analysis of randomized controlled trials. J.A.M.A., 293: 2257-2264.

Bowring dan Francis, 2011;

Brown C, Purich D. 1992. Physical-chemical prosecesses in kidney stone formation In : Coe F, Favus M, esd. Disorder of bone and mineral metabolism. New York, Raven Press, pp 613-624.

Brzoska MM, Moniuszko-Jakoniuk J, Pilat-Marcinkiewicz B, Sawicki B. 2003. Liver and kidney function and histology in rats exposed to cadmium and ethanol. Alcohol & Alcoholism 38(1): 2-10.

Cigiela, U., Folwarczna, J., Pytlik, M., and Zgorka, G. (2012) Effect of extracts from Trifolium medium L and Trifolium pratense L. on development of estrogen deficiency-induced osteoporosis in rats. Hindawi Publishing Corporation. Based Complemantary and Alternative Medicine. Article ID 921684.

Cooke, P.S., Naaz, A. (2004) Role of estrogens in adipocyte development and function. Exp. Biol. Med. 229: 1127–1135.

Fries JWU, Sandstrom DJ, Meyer TW, Rennke HG. 1989; Glomeruler hypertrophy and epithelial cell injury modulated progressive glomerulosclerosis in the rats. Blab Invest 60: 205-217.

Goltzman, D. (2002) Discoveries, drugs and skeletal disorders. Nat. Rev. drug Discov. 1: 784-796.

Halleen JM, Ranta R. 2001. Tartrate-resistant acid phosphatase as a serum marker of bone resorption. Am Clin Lab 20: 29–30.

Halleen JM, Alatalo SL, Suominen H, Cheng S, Janckila AJ, Vaananen HK. 2000. Tartrate-resistant acid phosphatase 5b: a novel serum marker of bone resorption. J Bone Miner Res 15: 1337–1345.

Hartiningsih, Nitisuwirjo, S., Wuryastuty, H., 2013. Respon tulang, ginjal dan kelenjar paratitoid tikus wistar yang mengkonsumsi pakan mengandung fosfor tinggi bervariasi. JSV 31(1) : 110-120.

Hartiningsih, Devita Anggraeni, Irkham Widiyono, Hastari Wuryastuty, 2015. Respon tulang femur tikus ovariohisterektomi yang mengkonsumsi kasein dan disuplementasi calcitriol selama 30 minggu. Jurnal Veteriner, 16(1): 68 – 77.

Hartiningsih, Devita Anggraeni, 2015. Suplementasi calcitriol menurunkan risiko osteoporosis tikus ovariektomi. Jurnal Sain Veteriner, 33(2): 143-148.

Hartiningsih, Devita Anggraeni, dan Sudarminto. 2016. Efektivitas diet teri tawar dan suplementasi kalsitriol untuk mencegah osteoporosis pada tikus ovariektomi. Jurnal Kedokteran Hewan, 10(1): 19-23.

Hartiningsih dan Anggraeni, D. ( 2016) Ekspresi Tartrate-resistant acid phosphatase 5b pada epifisis tulang femur tikus ovariektomi yang mengkonsumsi kombinasi Calcitriol dan Raloxifene. Jurnal Veteriner. 17: 1-10.

Hartiningsih, Puspitasari AD, Putri ND, Arifah N, Pawestri A, Anggraeni D. 2017 Kombinasi calcitriol dan ethynil ethyl estradiol meningkatkan ekskresi kalsium urin dan risiko urolitiasis pada tikus ovariektomi. Jurnal Veteriner. 18(2): 239-246.

Hartiningsih and Anggraeni D. 2017. The efectivitiveness of the combinations of calcitriol and ethynil ethyl estradiol to decrease osteoporosis and endometrial cancer risk in ovariectomized rats. Jurnal Kedokteran Hewan. 11(2): 50-56.

Hartiningsih dan Anggraeni D. 2018. Respon tulang femur tikus osteoporosis yang mengkonsumsi calcitriol. Jurnal Sain Veteriner 36(1): 1-10.

Hartiningsih, Anggraeni, D., Dhirgo Aji, D. (2012) Respon metafisis tulang femur distalis tikus ovariektomi yang mengkonsumsi kalsitriol. Jurnal Kedokteran Hewan 6: 92-98.

Hendy GN, Hruska KA, Mathew S, Goltzman,D. 2006. New insights into mineral and skeletal regulation by active forms of vitamin D. Kidney Int 69: 218-223.

Hoenderop JG, Muller D, Van Der Kemp AW, Hartog A, Suzuki M, Ishibashi K, Imai M, Sweep F, Willems PH, Van Os CH, Bindels RJ. 2001. Calcitriol controls the epithelial calcium channel in kidney. J Am Soc Nephrol 12: 1342–1349.

Janckila AJ, Takahasi K, Sun SZ, Yam LT. 2001. Tartrate-resistant acid phosphatase isoform 5b as serum marker for osteoclastic activity. Clin Chem 47: 74–80.

Justesen, J., Stenderus, K., Ebbesen, E.N., Moseklide, L., Steinche, T., Kassem, M. (2001) Adipocyte tissue volume in bone marrow is increased with aging and in patients with osteoporosis. Biogerontology, 2(3): 165-171.

Karsdal, MA., Martin, TJ., Bollerslev, J., Christiansen C., Henriksen K. (2007) Are nonresorbing osteoclasts sources of bone anabolic activity ? J. Bone Miner. Res. 22: 487-494.

Khosla, S., Melton, L.J., and Riggs, B.L. (2002) Estrogen and the male skeleton. J. Clin. Endocrinol. Metab. 87: 1443-1450.

Kong, J., Li, Y.C. (2006) Molecular mechanism of 1, 25-dihydroxyvitamin D3 inhibition of adipogenesis in 3T3-L1 cells. Am. J. Physiol Endocrinol Metab. 290: E916–E924.

Li F, Yang Y, Guo C, Zhang C, Yang Z, Li P. 2013. Antiosteoporotic activity of echinacoside in ovariectomized rats. Phytomedicine 15:20(6): 549-557.

Martin, T.J. and Sims, N.A. (2005) Osteoclast derived activity in the coupling of bone formation to resorption. Trend. Mol. Med., 11: 76-81.

Messina dan Wood, 2008;

Meyer TW, Rennke HG. 1988. Increased single nephrone protein excretion after renal ablation in nephritic rats. Am J Physiol 255: F1243-1248.

Mihai R, Faradon JR. 2000. Parathyroid disease and calcium metabolism. Britis Journal of Anaesthesia 85: 29-43.

Miller PL, Scholey JW, Rennke HG, Meyer TW. 1990. Glomeruler hypertrophy aggravates epithelial cell injury in nephritic rats. J Clin Invest 85: 1119-1126.

Mirkin dan Pickar (2013)

Mohr SB, Garland CF, Gorham ED, Grant WD, Garland FC. 2007. Is ultraviolet B irradiance inversely associated with incidence rates of endometrial cancer: an ecological study of 107 countries. Prev Med 45: 327-331.

Palmer N. 1993. Bones and Joints. In Pathology of domestic animals. Jubb, KVF., Kennedy PC, and Palmer N. ed. Academic Press, Inc, Harcourt Brace Jovanovich publishers, San Diego pp1-181.

Pan M, Li Z, Yeung V, Xu RJ. 2010. Dietary supplementationt of soy germ phytoestrogens or estradiol improves spatial memory performance and increases gene expression of BDNF, TrkB receptor and synaptic factors in ovariectomized rats. Nutrition and Metabolism 7: 75.

Potu, B.K., Nampurath, G.K., Chamallamudi, M.R., Prasad, K., Nayak, S.R., Dharmavarapu, P.K., Kedage, V., Bath, K.M., 2009. Evidence-based assesmaent antiosteoporotic activity of petrolium ether extract of ossus quadrangularis linn : on ovariectomy-induced osteoporosis. Ups J Med Sci. 114: 140-148.

Raisz, 2005).

Romagnoli, E., Mascia, M.L.,Cipriani, C., Fassino, V., Mazzei, F., D’Erasmo, E., Carnevale, V., Scillitani, A. and Minisola, S. (2008) Short and long-term variations in serum calciotropic hormones after a single very large dose of ergocalciferol (vitamin D2) or cholecalciferol (vitamin D3) in the elderly. J. Clin. Endrocrinol. & Metab., 93: 3015-3020.

Ribot dan Tremollieres, 2006),

Riggs, B.L., Khosla, S., and Melton, L.J. (2002) Sex steroids and the construction and conservation of the adult skeleton. Endocr. Rev. 23: 279-302.

Rizzoli, R., Boonen, S., Brandi, M.L., Burlet, N., Delmas, N., and Reginster, J.Y., (2008) The role of calcium and vitamin D in the management of osteoporosis. Bone, 42: 246-249.

Robertone JL. 1998. Chemically induced glomeruler injury: A review of basic mechanisms and specific xenobiotics. Toxicologic Pathologiy 26(1): 64-72.

Rodriguez, J.P., Garat, S., Gajardo, H., Pino, A.M., Seitz, G. (1999) Abnormal osteogenesis in osteoporotic patients is reflected by altered mesenchymal stem cells dynamics. J. Cell. Biochem. 75: 414–423.

Salazar-Martinez E, Lazcano-Ponce E, Sanchez-Zamorano L M, Gonzales-Lira G, Escudero-DE Los RP, Hernandes-Avila M. 2005. Dietary factors and endometrial cancer risk. Results of a case-control study in Mexico. In J Gynecol Cancer 15: 938-945.

Seamans, K.M. and Cashman, K.D. (2009) Existing and potentially novel functional marker of vitamin D status : a systematic review. Am. J. clin. nutr., 89: 1997S-2008S.

Seeman, E., Vellas, B., Benhamou, C., Aquino, J.P., Semler, J., Kaufman, J.M., Hoszowski, K., Varela, A.R., Fiore, C., Brixen, K., reginster, J.Y., Boonen, S., (2006) Strontium ranelate reduce the risk of vertebral and nonvertebral fractures in women eighty years of age and older. J. Bone Miner. Res. 21: 1113-1120.

Selby PL, Davies M, Marks JS, Mawer EB. 1995. Vitamin D intoxication causes hypercalcemia by increased bone resorption which responds topamidronate. Clin Endocrinol 43: 531-536.

Shiizaki K, Hatamura I, Negi S, Nakazawa E, Tozawa R, Izawa S, Akizawa T, Kusano E. 2008. Cellular changes following direct vitamin D injection into the uraemia-induced hyperplastic parathyroid gland. NDT Plus 1 (suppl 3): iii42-iii48.

Shiraishi A, Takeda S, Masaki T, Higuchi Y, Uchiyama Y, Kubodera N, Sato K, Ikeda K, Nakamura T, Matsumoto T, Ogata E. 2000. Alfacalcidol inhibits bone resorption and stimulates formation in an ovariectomized rat model of osteoporosis: distinct actions from estrogen. J bone Miner Res 15: 235-244.

Shiud et al., 2009).

Shuid, A.N., Ping, L.L., Muhammad, N., Soelaiman, I.N., 2011. The effects of labisia pumila var alata on bone markers and bone calcium in a rat model of post-menopausal osteoporosis. Ehnopharmacol. 133(2): 538-542.

Silva PTD, Oloris SCS, Avanzo JL, Fukumasu H, Silva da TC, Hernandez-Blazquez FJ, Dagli MLZ. 2008. Compensatory kidney hypertrophy/hyperplasia after nephrectomy in mice : alterations of connexin 43 (Cx43) phosphorylated isoforms. Braz J Vet Pathol 1(1): 3-9.

Song Y, Fleet JC. 2007. Intestinal resistence to 1,25 Dihydroxyvitamin D in Mice Heterzygous for the Vitamin D Receptor Knouckout Allele. Endocrinology 148 (3): 1396-1402.

Sun X, Zemel MB. 2004. Role of uncoupling protein 2 (UCP2) expression and 1alpha, 25-dihydroxyvitamin D3 in modulating adipocyte apoptosis. Faseb J 18: 1430–1432.

Teitelbaum SL, Ross FP. 2003. Genetic regulation of osteoclast development and function. Nat Rev Genet 4: 638-649.

Teoh SL, Latief AA. 2010. Histological changes in the kidney of experimental diabetic rats fed with Momordica charantia (bitter gourd) extract. Romanian Journal of morphology and embryology 5(1): 91-95.

Udell et al., 2006;

Vaananen HK, Zhao H, Mulari M, Halleen JM. 2000. The cell biology of osteoclast function. J Cell Sci 113: 377– 81.

Van Abel M, Hoenderop JG, van der Kemp AW, van Leeuwen JP. Bindels RJ. 2003. Regulation of the epithelial Ca2+ channels in small intestine as studied by quantitative mRNA detection. Am J Physiol Gastrointest Liver Physiol 285: 978–985.

Van Cromphaut SJ, Dewerchin M, Hoenderop JG, Stockmans I, Van Herck E, Kato S, Bindels RJ, Collen D, Carmeliet P, Bouillon R, Carmeliet G. 2001. Duodenal calcium absorption in vitamin D receptor-knockout mice: functional and molecular aspects. Proc Natl Acad Sci USA 98: 13324–13329.

Van de Graaft SF, Boullart I, Hoenderop JG, Bindels RJ. 2004. Regulation of the epithelial Ca2+ channels TRPV5 and TRPV6 by 1α,25 dihydroxy vitamin D3 and dietary Ca2+. J Steroid Biochem Mol Biol 89-90: 303-308.

Weisberg, S.P, McCann, D., Desai, M., Rosenbaum, M., Leibel, R.L., Ferrante, A.W. Jr. (2003) Obesity is associated with macrophage accumulation in adipose tissue. J Clin Invest. 112(12): 1785-1808.

Verma, S., Rajaratnam J.H., Denton J., Hoyland J.A., Byers R.J. (2002) Adipocytic proportion of bone marrow is inversely related to bone formation in osteoporosis. J Clin. Pathol. 55: 693-698.

Vieth R, Milojevic S, Peltekova V. 2000. Improved cholecalciferol nutrition in rats is noncalcemic, suppresses parathyroid hormone and increases responsiveness to 1,25 dihydroxycholecalciferol. J Nutr 130: 578-584.

Wood, R.J., Fleets, J.C., Cashman, K., Bruns, M.E., Deluca, H.F., (1998) Intestinal calcium Absorption in the Aged rats : Evidence of Intestinal resistence to 1,25(OH)2 Vitamin D. Endocrinology, 39(9): 3843-3848.

Yacobus CH, Holick, MF, Shao Q. 1992. Hypervitaminosis associated with drinking milk. N Engl J Med 326: 1173-1177.

Yoshida Y, Fogo A, and Ichikawa I. 1989. Glomeruler hemodynamic changes vs hypertrophy in experimental glomerular sclerosis. Kidney Int 35: 654-660.

Zarate, A., Hernandez-Valencia, M., Saucedo, R., Basurto, L., Manuel-Apolinar, L., 2014. Current position about the use of estrogen therapy in women during the menopause period. Review of Medical Instruments. 52(1): 66-69.

Zhou, Y.S., Liu, Y.S., Tan, J.G. (2006) Is 1, 25-dihydroxyvitamin D3 an ideal substitute for dexamethasone for inducing osteogenic differentiation of human adipose tissue-derived stromal cells in vitro? Chin. Med. J. (Engl). 119: 1278–1286.



DOI: https://doi.org/10.22146/jsv.47032

Article Metrics

Abstract views : 648 | views : 629

Refbacks

  • There are currently no refbacks.




Copyright (c) 2021 Jurnal Sain Veteriner

Creative Commons License
This work is licensed under a Creative Commons Attribution-ShareAlike 4.0 International License.

Jurnal Sain Veteriner Indexed by

    CrossrefROADCOREDimensions  JournalTOCs   


Copyright of JSV (Jurnal Sain Veteriner) ISSN 0126-0421 (print), ISSN 2407-3733 (online).

Fakultas Kedokteran Hewan, Universitas Gadjah Mada

Jl. Fauna No.2, Karangmalang, Yogyakarta

Phone: 0274-560862

Fax: 0274-560861

Email: jsv_fkh@ugm.ac.id

Jurnal Sain Veteriner is licensed under a Creative Commons Attribution-ShareAlike 4.0 International License.

 

free
web stats View My Stats