Skip to main content
SpringerLink
Log in

The protective and therapeutic effect of exclusive and combined treatment with alpha-ketoglutarate sodium salt and ipriflavone on bone loss in orchidectomized rats

  • Published:
The journal of nutrition, health & aging

Abstract

Objective

This study investigated the effect of alpha-ketoglutarate sodium salt (AKG) and ipriflavone (IP) treatment on the mineralization of the tibia in male rats during the development and after the establishment of osteopenia.

Design

One hundred and twenty eight male rats were randomly selected and submitted to either sham-operation (SHO) or orchidectomy (ORX), after which each group were then randomly divided between the two experiments. In Experiment-1, treatment with AKG or/and IP started after a 7-day recovery period, whereas in Experiment-2, the experimental protocol proceeded after a 60-day period of osteopenia establishment. AKG was then administered as an experimental drinking, at a concentration of 1.0 mol/l. As a control, a placebo solution was administered. IP at 50 mg/kg b.w., and physiological saline–PhS (as a control for IP) were applied daily via gavage.

Measurements

After 60 days of experimental treatment, in both experiments, the rats were sacrificed, their body weight recorded, while blood serum (Osteocalcin, CTX) and isolated tibia (weight, length, pQCT, DXA, 3-point bending test) were stored for further analysis.

Results and conclusions

Our results show that during the development of osteopenia, AKG and IP when applied exclusively, counteracts osteopenia development, whereas their usage after the establishment of osteopenia, significantly limits the development of bone disorders. Furthermore, combined treatment of AKG and IP exceeded the effects of their sole usage. In addition, during the development of osteopenia, AKG and IP not only inhibited bone resorption, but markedly stimulated the formation of bone tissue. Finally, after the development of osteopenia, combined treatment with AKG and IP protected the bone tissue against orchidectomy-induced bone loss.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Table 1
Table 2
Figure 1
Figure 2
Table 3
Table 4
Table 5

Similar content being viewed by others

References

  1. Dawson-Hughes B, National Osteoporosis Foundation Guide C. A revised clinician’s guide to the prevention and treatment of osteoporosis. J Clin Endocrinol Metab 2008;93:2463–2465.

    Article  CAS  PubMed  Google Scholar 

  2. Lambert JK, Zaidi M, Mechanick JI. Male osteoporosis: epidemiology and the pathogenesis of aging bones. Curr Osteoporos Rep 2011;9:229–236.

    Article  PubMed  Google Scholar 

  3. Ahlborg HG, Johnell O, Turner CH, Rannevik G, Karlsson MK. Bone loss and bone size after menopause. N Engl J Med 349:327–334.

  4. Daniell HW. Osteoporosis after orchiectomy for prostate cancer. J Urol 1997;157:439–444.

    Article  CAS  PubMed  Google Scholar 

  5. Bilezikian JP, Morishima A, Bell J, Grumbach MM. Increased Bone Mass as a Result of Estrogen Therapy in a Man With Aromatase Deficiency. Obstet Gynecol Surv 1999;54:114–116.

    Article  Google Scholar 

  6. Lorenc RS, Misiorowski W, Karczmarewicz E. Critical points in strategies for the diagnosis and treatment of osteoporosis. Endokrynol Pol 2009;60:124–133.

    PubMed  Google Scholar 

  7. Vogel VG, Costantino JP, Wickerham DL, Cronin WM, Cecchini RS, Atkins JN, Bevers TB, Fehrenbacher L, Pajon ER, Jr., Wade JL, 3rd, Robidoux A, Margolese RG, James J, Lippman SM, Runowicz CD, Ganz PA, Reis SE, McCaskill-Stevens W, Ford LG, Jordan VC, Wolmark N. Effects of tamoxifen vs raloxifene on the risk of developing invasive breast cancer and other disease outcomes: the NSABP Study of Tamoxifen and Raloxifene (STAR) P-2 trial. JAMA 2006;295:2727–2741.

    Article  CAS  PubMed  Google Scholar 

  8. Radzki RP, Bienko M, Pierzynowski SG. Anti-osteopenic effect of alphaketoglutarate sodium salt in ovariectomized rats. J Bone Miner Metab 2012;30:651–659.

    Article  CAS  PubMed  Google Scholar 

  9. Gordon MK, Hahn RA. Collagens. Cell Tissue Res 2010;339:247–257.

    Article  CAS  PubMed  Google Scholar 

  10. Fayh AP, Friedman R, Sapata KB, Oliveira AR. Effect of L-arginine supplementation on secretion of human growth hormone and insulin-like growth factor in adults. Arq Bras Endocrinol Metabol 2007;51:587–592.

    Article  PubMed  Google Scholar 

  11. Harrison AP, Tygesen MP, Sawa-Wojtanowicz B, Husted S, Tatara MR. Alphaketoglutarate treatment early in postnatal life improves bone density in lambs at slaughter. Bone 2004;35:204–209.

    Article  CAS  PubMed  Google Scholar 

  12. Cotter AA, Cashman KD. The effect of two dietary and a synthetic phytoestrogen on transepithelial calcium transport in human intestinal-like Caco-2 cells. Eur J Nutr 2005;44:72–78.

    Article  CAS  PubMed  Google Scholar 

  13. Tsutsumi N, Kawashima K, Nagata H, Tsuyuki J, Itoh F, Arai N, Kojima M, Ujiie A, Endo H. Effects of KCA-098 on bone metabolism: comparison with those of ipriflavone. Jpn J Pharmacol 1994;65:343–349.

    Article  CAS  PubMed  Google Scholar 

  14. Giossi M, Caruso P, Civelli M, Bongrani S. Inhibition of parathyroid hormonestimulated resorption in cultured fetal rat long bones by the main metabolites of ipriflavone. Calcif Tissue Int 1996;58:419–422.

    Article  CAS  PubMed  Google Scholar 

  15. Arjmandi BH, Khalil DA, Hollis BW. Ipriflavone, a synthetic phytoestrogen, enhances intestinal calcium transport in vitro. Calcif Tissue Int 2000;67:225–229.

    Article  CAS  PubMed  Google Scholar 

  16. Bienko M, Radzki RP, Puzio I, Filip R, Pierzynowski SG, Studzinski T. AKG a potential therapeutic drug agent in the treatment of osteoporose like skeletal system disorders. Bone (Suppl), 2003;5:S223.

    Google Scholar 

  17. Sawa-Wojtanowicz B, Pierzynowski SG, Studzinski T. Effect of alpha-ketoglutarate (AKG) and L-alanyl-Lglutamine (Ala-Gln) on the development of the skeletal system in the postnatal life in the pig investigated on the model of ribs. Acta Orthop Scand 2002;73 (Suppl 304):51.

    Google Scholar 

  18. Dobrowolski P, Tomaszewska E, Bienko M, Radzki RP, Pierzynowski SG. The effect of dietary administration of 2-oxoglutaric acid on the cartilage and bone of growing rats. Br J Nutr 2013;110:651–658.

    Article  CAS  PubMed  Google Scholar 

  19. Radzki RP, Bienko M, Puzio I, Filip R, Pierzynowski SG, Studzinski T. Th effect of alpha-ketoglutarate (AKG) on mineralization of femur in ovariectomized rats. Acta Orthop Scand, 2002;73 (Suppl 304):52.

    Google Scholar 

  20. Filip RS, Pierzynowski SG, Lindegard B, Wernerman J, Haratym-Maj A, Podgurniak M. Alpha-ketoglutarate decreases serum levels of C-terminal cross-linking telopeptide of type I collagen (CTX) in postmenopausal women with osteopenia: sixmonth study. Int J Vitam Nutr Res 2007;77:89–97.

    Article  CAS  PubMed  Google Scholar 

  21. Arjmandi BH, Birnbaum RS, Juma S, Barengolts E, Kukreja SC. The synthetic phytoestrogen, ipriflavone, and estrogen prevent bone loss by different mechanisms. Calcif Tissue Int 2000;66:61–65.

    Article  CAS  PubMed  Google Scholar 

  22. Civitelli R. In vitro and in vivo effects of ipriflavone on bone formation and bone biomechanics. Calcif Tissue Int 1997;61 Suppl 1:S12–14.

    Article  CAS  PubMed  Google Scholar 

  23. Makita K, Ohta H. Ipriflavone in the treatment of osteoporosis. Nippon Rinsho 60 Suppl 3:359–364.

  24. de Aloysio D, Gambacciani M, Altieri P, Ciaponi M, Ventura V, Mura M, Genazzani AR, Bottiglioni F. Bone density changes in postmenopausal women with the administration of ipriflavone alone or in association with low-dose ERT. Gynecol Endocrinol 1997;11:289–293.

    Article  CAS  PubMed  Google Scholar 

  25. Morrow R, Deyhim F, Patil BS, Stoecker BJ. Feeding orange pulp improved bone quality in a rat model of male osteoporosis. J Med Food 2009;12:298–303.

    Article  CAS  PubMed  Google Scholar 

  26. Urasopon N, Hamada Y, Asaoka K, Cherdshewasart W, Malaivijitnond S. Pueraria mirifica, a phytoestrogen-rich herb, prevents bone loss in orchidectomized rats. Maturitas 2007;56:322–331.

    Article  CAS  PubMed  Google Scholar 

  27. Chachra D, Lee JM, Kasra M, Grynpas MD. Differential effects of ovariectomy on the mechanical properties of cortical and cancellous bone in rat femora and vertebrae. Biomed Sci Instrum 2000;36:123–128.

    CAS  PubMed  Google Scholar 

  28. Ferretti JL, Cointry GR, Capozza RF, Frost HM. Bone mass, bone strength, musclebone interactions, osteopenias and osteoporoses. Mech Ageing Dev 2003;124:269–279.

    Article  PubMed  Google Scholar 

  29. Radzki RP, Bienko M, Filip RS, Albera E, Kankofer M. Effect of strontium ranelate on femur densitometry and antioxidative/oxidative status in castrated male rats. Scand J Lab Anim Sci 2009;36:193–201.

    CAS  Google Scholar 

  30. Blouin S, Libouban H, Moreau MF, Chappard D. Orchidectomy models of osteoporosis. Methods Mol Biol 2008;455:125–134.

    Article  PubMed  Google Scholar 

  31. Dobrowolski P, Tomaszewska E, Radzki RP, Bienko M, Wydrych J, Zdybel A, Pierzynowski SG. Can 2-oxoglutarate prevent changes in bone evoked by omeprazole? Nutrition 2013;29:556–561.

    Article  CAS  PubMed  Google Scholar 

  32. Dobrowolski PJ, Piersiak T, Surve VV, Kruszewska D, Gawron A, Pacuska P, Hakanson R, Pierzynowski SG. Dietary alpha-ketoglutarate reduces gastrectomyevoked loss of calvaria and trabecular bone in female rats. Scand J Gastroenterol 2008;43:551–558.

    Article  CAS  PubMed  Google Scholar 

  33. Kim BT, Mosekilde L, Duan Y, Zhang XZ, Tornvig L, Thomsen JS, Seeman E. The structural and hormonal basis of sex differences in peak appendicular bone strength in rats. J Bone Miner Res. 2003;18:150–155.

    Article  CAS  PubMed  Google Scholar 

  34. Saxon LK, Turner CH. Estrogen receptor beta: the antimechanostat? Bone 36:185–192.

  35. Notoya K, Yoshida K, Tsukuda R, Taketomi S. Effect of ipriflavone on expression of markers characteristic of the osteoblast phenotype in rat bone marrow stromal cell culture. J Bone Miner Res 1994;9:395–400.

    Article  CAS  PubMed  Google Scholar 

  36. Jamal SA, Hamilton CJ. Nitric oxide donors for the treatment of osteoporosis. Curr Osteoporos Rep 2012;10:86–92.

    Article  PubMed  Google Scholar 

  37. Wimalawansa SJ. Nitric oxide: new evidence for novel therapeutic indications. Expert Opin Pharmacother 2008;9:1935–1954.

    Article  CAS  PubMed  Google Scholar 

  38. Pierzynowski SG, Sjodin A. Perspectives of glutamine and its derivatives as feed additives for farm animals. J Anim Feed Sci 1998;7:79–91.

    Google Scholar 

  39. Hagiwara H, Naruse M, Adachi C, Inoue A, Hiruma Y, Otsuka E, Naruse K, Demura H, Hirose S. Ipriflavone down-regulates endothelin receptor levels during differentiation of rat calvarial osteoblast-like cells. J Biochem 1999;126:168–173.

    Article  CAS  PubMed  Google Scholar 

  40. Yao J, Zhang J, Hou JF. Effects of ipriflavone on caged layer bone metabolism in vitro and in vivo. Poult Sci 2007;86:503–507.

    Article  CAS  PubMed  Google Scholar 

  41. Kathleen A, Head ND. Ipriflavone: An important Bone-Building Isoflavone. Altern Med Rev 4:10–22.

  42. Ghezzo C, Civitelli R, Cadel S, Borelli G, Maiorino M, Bufalino L, Bongrani S. Ipriflavone does not alter bone apatite crystal structure in adult male rats. Calcif Tissue Int 1996;59:496–499.

    Article  CAS  PubMed  Google Scholar 

  43. Agnusdei D, Civitelli R, Camporeale A, Parisi G, Gennari L, Nardi P, Gennari C. Age-related decline of bone mass and intestinal calcium absorption in normal males. Calcif Tissue Int 1998;63:197–201.

    Article  CAS  PubMed  Google Scholar 

  44. Takeuchi N, Go S, Murase M, Nomura Y, Takase H, Uchida K. Effects of castration and testosterone administration on serum lipoproteins and their apoproteins in male spontaneously hypertensive rat. Endocrinology 1986;118:1787–1794.

    Article  CAS  PubMed  Google Scholar 

  45. Wegorzewska IN, Walters K, Weiser MJ, Cruthirds DF, Ewell E, Larco DO, Handa RJ, Wu TJ. Postovariectomy weight gain in female rats is reversed by estrogen receptor alpha agonist, propylpyrazoletriol. Am J Obstet Gynecol 2008;199:e1–5.

    Article  Google Scholar 

  46. Radzki RP, Bieńko M, Pierzynowski SG. The effect of dietary alpha-ketoglutarate on the blood lipid profile during hypercholesterolemia in rats. Scan J Clin Lab Invest 2009;69:175–180.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Animal Physiology, Faculty of Veterinary Medicine, University of Life Sciences in Lublin, Lublin, Poland

    R. P. Radzki & M. Bieńko

  2. Department of Clinical Endoscopy, Institute of Rural Health, Lublin, Poland

    R. Filip

  3. Department Biology, Lund University, Sölvegatan 35, 22362, Lund, Sweden

    S. G. Pierzynowski

  4. Department Medical Biology, Institute of Rural Health, Lublin, Poland

    S. G. Pierzynowski

Authors
  1. R. P. Radzki
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. M. Bieńko
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. R. Filip
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. S. G. Pierzynowski
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to R. P. Radzki.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Radzki, R.P., Bieńko, M., Filip, R. et al. The protective and therapeutic effect of exclusive and combined treatment with alpha-ketoglutarate sodium salt and ipriflavone on bone loss in orchidectomized rats. J Nutr Health Aging 20, 628–636 (2016). https://doi.org/10.1007/s12603-015-0654-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12603-015-0654-1

Key words

Search

Navigation