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Increase of Liver Organ Weight in B6C3F1 Mice Fed with High dose Stevioside for 14 Days

  • Received : 2012.03.15
  • Accepted : 2012.07.04
  • Published : 2012.09.30

Abstract

Stevioside, a natural sweeteners presently used in various kinds of food and food products in Korea, was evaluated for its toxicity potential in the 14 day feeding study using B6C3F1 mice. Stevioside was added to the diet at different concentrations of 0.31, 0.62, 1.25, 2.5 and 5%, and was administered for 14 consecutive days. An increase of liver organ weight in male mice was observed. No diet-related differences were noted in clinical signs, food consumption, and gross and histopatholgical evaluation. Based on these results, we concluded that the concentration of 5% in the diet was a suitable maximum tolerable dose of stevioside for a 90 day study in mice.

Keywords

References

  1. Forshee, R.A. and Storey, M.L. Total beverage consumption and beverage choices among children and adolescents. Int. J. Food Sci. Nutr., 87, S287-S291 (2003).
  2. JECFA Steviol glycosides, in 63rd Meeting of the Joint FAO/ WHO Expert Committee on Food Additives. WHO Technical Report Series 928. World Health Organization: Geneva, 34-39 and 138 (2005).
  3. Lee, B.M. and Kim, H.I. Stevioside, a natural sweetner: Is it safe? J. Fd. Hyg. Safety, 11(4), 323-327 (1996).
  4. Choi, D.W., Kim, J.H., Cho, S.Y., Kim, D.H. and Chang, S.Y. Regulation and quality control of herbal drugs in korea. Toxicology, 181-182, 581-586 (2002). https://doi.org/10.1016/S0300-483X(02)00487-0
  5. Compadre, C.M., Hussain, R.A., Nanayakkara, N.P., Pezzuto, J.M. and Kinghorn, A.D. Mass spectral analysis of some derivatives and in vitro metabolites of steviol, the aglycone of the natural sweetners, stevioside, rebaudioside A, and rubusoside. Biomed. Environ. Mass spectrum., 15(4), 211-222 (1988). https://doi.org/10.1002/bms.1200150405
  6. Chaturvedula, V.S. and Prakash, I., A new diterpene glycoside from stevia rebaudiana. Molecules, 16(4), 2937-2943 (2011). https://doi.org/10.3390/molecules16042937
  7. Koyama, E., Sakai, N., Ohori, Y., Kitazawa, K., Fujino, A. and Ui, M. Absorption and metabolism of glycosidic sweetners of stevia mixture and their aglycone, steviol, in rats and humans. Food Chem.Toxicol., 41, 875-883 (2003a). https://doi.org/10.1016/S0278-6915(03)00039-5
  8. Koyama, E., Kitazawa, K., Ohori, Y., Izawa, O., Kakegawa, K., Fujino, A. and Ui, M. In vitro metabolism of the glycoside sweetners, stevia mixture and enzymatically modified stevia in human intestinal microflora. Food Chem. Toxicol., 41, 359-374 (2003b). https://doi.org/10.1016/S0278-6915(02)00235-1
  9. Wingard, R.E.Jr., Brown, J.P., Enderlin, F.E., Dale, J.A., Hale, R.L. and Seitz, C.T. Intestinal degradation and absorption of the glycosidic sweeteners stevioside and rebaudioside A. Experientia, 36, 519-520 (1980). https://doi.org/10.1007/BF01965774
  10. Hutapea, A.M., Toskulkao, C., Buddhasukh, D., Wilairat, P. and Glinsukon, T. Digestion of stevioside, a natural sweetener, by various digestive enzymes. J. Clin. Biochem. Nutr., 23, 177-186 (1997). https://doi.org/10.3164/jcbn.23.177
  11. Gardana, C., Simonetti, P., Canzi, E., Zanchi, R. and Pietta, P. Metabolism of stevioside and rebaudioside A from stevia rebaudiana extracts by human microflora. J. Agric. Food Chem., 51, 6618-6622 (2003). https://doi.org/10.1021/jf0303619
  12. Liu, J.C., Kao, P.K., Chan, P., Hsu, Y.H., Hou, C.C., Lien, G.S., Hsieh, M.H., Chen, Y.J. and Cheng, J.T. Mechanism of the antihypertensive effect of stevioside in anesthetized dogs. Pharmacology, 67(1), 14-20 (2003). https://doi.org/10.1159/000066782
  13. Kujur, R.S., Singh, V., Ram, M., Yadava, H.N., Singh, K.K., Kumari, S. and Roy, B.K. Antidiabetic activity and phytochemical screening of crude extract of Stevia rebaudiana in alloxan-induced diabetic rats. Pharmacognosy Res., 2(4), 258-263 (2010). https://doi.org/10.4103/0974-8490.69128
  14. Ferri, L.A., Alves-Do-Prado, W., Yamada, S.S., Gazola, B., Batista, M.R. and Bazotte, R.B. Phytother Res., 20(9), 732-736 (2006). https://doi.org/10.1002/ptr.1944
  15. Sharma, D., Puri, M., Tiwary, A.K., Singh, N. and Jaggi, A.S. Antiamnesic effect of stevioside in scopolamine-treated rats. Indian J. Pharmacol., 42(3), 164-167 (2010). https://doi.org/10.4103/0253-7613.66840
  16. Takasaki, M., Konoshima, T., Kozuka, M., Tokuda, H., Takayasu, J., Nishino, H., Miyakoshi, M., Mizutani, K. and Lee, K.H. Bioorg. Med. Chem., 15-17(2), 600-605 (2009).
  17. Chatsudthipong, V. and Muanprasat, C. Stevioside and related compounds : therapeutic benefits beyond sweetness. Pharmacol. Ther., 121(1), 41-54 (2009). https://doi.org/10.1016/j.pharmthera.2008.09.007
  18. Boonkaewwan, C., Toskulkao, C. and Vongsakul, M. Antiinflammatory and immunomodulatory activities of stevioside and its metabolite steviol on THP-1 cells. J. Agric. Food Chem., 54(3), 785-789 (2006). https://doi.org/10.1021/jf0523465
  19. Cekic, V., Vasovic, V., Jakovljevic, V., Mikov, M. and Sabo, A. Hypoglycaemic action of stevioside and a barley and brewer's yeast based preparation in the experimental model on mice. Bosn. J. Basic Med. Sci., 11(1), 11-16 (2011).
  20. Toskulkao, C., Chaturat, L., Temcharoen, P. and Glinsukon, T. Acute toxicity of stevioside, a natural sweetener, and its metabolite, steviol, in several animal species. Drug Chem. Toxicol., 20(1-2), 31-44 (1997). https://doi.org/10.3109/01480549709011077
  21. Aze, Y., Toyoda, K., Imaida, K., Hayashi, S., Imazawa, T., Hayashi, Y. and Takahashi, M. Subchronic oral toxicity study of stevioside in F344 rats. Eisei Shikenjo Hokoku., 109, 48-54 (1991).
  22. Toyada, K., Matsui, H., Shoda, T., Uneyama, C., Takada, K. and Takahashi, M. Assessment of the carcinogenicity of stevioside in F344 rats. Food Chem. Toxicol., 35(6), 597-603 (1997). https://doi.org/10.1016/S0278-6915(97)00023-9
  23. Nikiforov, A.I. and Eapen, A.K. A 90-day oral(dietary) toxicity study of rebaudioside A in Sprague-Dawley rats. Int. J. Toxicol., 27(1), 65-80 (2008). https://doi.org/10.1080/10915810701876752
  24. Awney, H.A., Massoud, M.I. and El-Maghrabi, S. Long-term feeding effects of stevioside sweetener on some toxicological parameters of growing male rats. J. Appl. Toxicol., doi: 10 (2010).
  25. Geuns, J.M., Augustijns, P., Mols, R., Buyse, J.G. and Driessen, B. Metabolism of stevioside in pigs and intestinal absorption characteristics of stevioside, rebaudioside A and steviol. Food Chem. Toxicol., 41, 1599-1607 (2003). https://doi.org/10.1016/S0278-6915(03)00191-1
  26. Roberts, A. and Renwick, A.G. Comparative toxicokinetics and metabolism of rebaudioside A, stevioside, and steviol in rats. Food Chem. Toxicol., 46(7), S31-S39 (2008). https://doi.org/10.1016/j.fct.2008.05.006
  27. Wheeler, A., Boileau, A.C., Winkler, P.C., Compton, J.C., Prakash, I., Jiang, X. and Mandarino, D.A. Pharmacokinetics of rebaudioside A and stevioside after single oral doses in healthy men. Food Chem. Toxicol., 46(7), S54-S60 (2008). https://doi.org/10.1016/j.fct.2008.04.041