Skip to main content
Log in

Evaluation of 90-day Repeated Dose Oral Toxicity, Glycometabolism, Learning and Memory Ability, and Related Enzyme of Chromium Malate Supplementation in Sprague-Dawley Rats

  • Published:
Biological Trace Element Research Aims and scope Submit manuscript

Abstract

Our previous study showed that chromium malate improved the regulation of blood glucose in mice with alloxan-induced diabetes. The present study was designed to evaluate the 90-day oral toxicity of chromium malate in Sprague-Dawley rats. The present study inspected the effect of chromium malate on glycometabolism, glycometabolism-related enzymes, lipid metabolism, and learning and memory ability in metabolically healthy Sprague-Dawley rats. The results showed that all rats survived and pathological, toxic, feces, and urine changes were not observed. Chromium malate did not cause measurable damage on liver, brain, and kidney. The fasting blood glucose, serum insulin, insulin resistance index, C-peptide, hepatic glycogen, glucose-6-phosphate dehydrogenase, glucokinase, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglyceride levels of normal rats in chromium malate groups had no significant change when compared with control group and chromium picolinate group under physiologically relevant conditions. The serum and organ content of Cr in chromium malate groups had no significant change compared with control group. No significant changes were found in morris water maze test and superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and true choline esterase (TChE) activity. The results indicated that supplementation with chromium malate did not cause measurable toxicity and has no obvious effect on glycometabolism and related enzymes, learning and memory ability, and related enzymes and lipid metabolism of female and male rats. The results of this study suggest that chromium malate is safe for human consumption.

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

Access this article

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

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  1. Economou-Eliopoulos M, Frei R, Atsarou C (2014) Application of chromium stable isotopes to the evaluation of Cr(VI) contamination in groundwater and rock leachates from central Euboea and the Assopos basin (Greece). Catena 122:216–228

    Article  CAS  Google Scholar 

  2. Parksa JL, McNeill L, Edwards M (2014) NOM and alkalinity interference in trace-level hexavalent chromium analysis. Talanta 130:226–232

    Article  Google Scholar 

  3. Li Y, Li P, Yu SF, Zhang J, Wang TC, Jia G (2014) miR-3940-5p associated with genetic damage in workers exposed to hexavalent chromium. Toxicol Lett 229:319–326

    Article  CAS  PubMed  Google Scholar 

  4. Hend MAEA, Amal AEB, Afaf MA, Ahmed L, Shery SK, Ayman ZE, Hussein AA (2014) DNA fragmentation, caspase 3 and prostate-specific antigen genes expression induced by arsenic, cadmium, and chromium on nontumorigenic human prostate cells. Biol Trace Elem Res 162:95–105

    Article  Google Scholar 

  5. Suh M, Thompson CM, Kirman CR, Carakostas MC, Hawse LC, Harris MA, Proctora DM (2014) High concentrations of hexavalent chromium in drinking water alter iron homeostasis in F344 rats and B6C3F1 mice. Food Chem Toxicol 65:381–388

    Article  CAS  PubMed  Google Scholar 

  6. Stanley JA, Sivakumar KK, Arosh JA, Burghardt RC, Banu SK (2014) Edaravone mitigates hexavalent chromium-induced oxidative stress and depletion of antioxidant enzymes while estrogen restores antioxidant enzymes in the rat ovary in F1 offspring. Biol Reprod 91:12. doi: 10.1095/biolreprod.113.113332

  7. Deb DD, Parimala G, Devi SS, Chakrabarti T (2012) Role of Carum copticum seeds in modulating chromium-induced toxicity on human bronchial epithelial cells and human peripheral blood lymphocytes. Exp Toxicol Pathol 64:889–897

    Article  CAS  PubMed  Google Scholar 

  8. Di Bona KR, Love S, Rhodes NR, McAdory D, Sinha SH, Kern N, Kent J, Strickland J, Wilson A, Beaird J (2011) Chromium is not an essential trace element for mammals: effects of a “low-chromium” diet. J Biol Inorg Chem 16:381–390

    Article  PubMed  Google Scholar 

  9. Rudolf E, Cervinka M (2009) Trivalent chromium activates Rac-1 and Src and induces switch in the cell death mode in human dermal fibroblasts. Toxicol Lett 188:236–242

    Article  CAS  PubMed  Google Scholar 

  10. Lewicki S, Zdanowski R, Krzyzowska M, Lewicka A, Debski B, Niemcewicz M, Goniewicz M (2014) The role of Chromium III in the organism and its possible use in diabetes and obesity treatment. Ann Agric Environ Med 21:331–335

    Article  PubMed  Google Scholar 

  11. Yoshida M, Hatakeyama E, Hosomi R, Kanda S, Nishiyama T, Fukunaga K (2010) Tissue accumulation and urinary excretion of chromium in rats fed diets containing graded levels of chromium chloride or chromium picolinate. J Toxicol Sci 35:485–491

    Article  CAS  PubMed  Google Scholar 

  12. De Lucca PC, Dutrey PL, Villarino ME, Ubios AM (2009) Effect of different doses of hexavalent chromium on mandibular growth and tooth eruption in juvenile Wistar rats. Exp Toxicol Pathol 61:347–352

    Article  PubMed  Google Scholar 

  13. Farshchi A, Nikfar S, Seyedifar M, Abdollahi M (2013) Effect of chromium on glucose and lipid profiles in patients with type 2 diabetes; a meta-analysis review of randomized trials. J Pharm Pharm Sci 16:99–114

    PubMed  Google Scholar 

  14. Li F, Wu XY, Zou YM, Zhao T, Zhang M, Feng WW, Yang LQ (2012) Comparing anti-hyperglycemic activity and acute oral toxicity of three different trivalent chromium complexes in mice. Food Chem Toxicol 50:1623–1631

    Article  CAS  PubMed  Google Scholar 

  15. Wu XY, Li F, Xu WD, Zhao JL, Zhao T, Liang LH, Yang LQ (2011) Anti-hyperglycemic activity of chromium (III) malate complex in alloxan-induced diabetic rats. Biol Trace Elem Res 143:1031–1043

    Article  CAS  PubMed  Google Scholar 

  16. Zhang Q, Xiao XH, Li M, Li WH, Yu M, Zhang HB, Ping F, Wang ZX, Zheng J, Xiang HD (2014) miR-375 and miR-30d in the rffect of chromium-containing Chinese medicine moderating glucose metabolism. J Diabetes Res 2014:1–6

    Google Scholar 

  17. Leiva T, Cooke RF, Aboin AC, Drago FL, Gennari R, Vasconcelos JLM (2014) Effects of excessive energy intake and supplementation with chromium propionate on insulin resistance parameters in nonlactating dairy cows. J Anim Sci 92:775–782

    Article  CAS  PubMed  Google Scholar 

  18. Preuss HG, Echard B, Bagchi D, Perricone NV (2013) Comparing effects of carbohydrate (CHO) blockers and trivalent chromium on CHO-induced insulin resistance and elevated blood pressure in rats. J Am Coll Nutr 32:58–65

    Article  CAS  PubMed  Google Scholar 

  19. Hoffman NJ, Penque BA, Habegger KM, Sealls W, Tackett L, Elmendorf JS (2014) Chromium enhances insulin responsiveness via AMPK. J Nutr Biochem 25:565–572

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  20. Suksomboon N, Poolsup N, Yuwanakorn A (2014) Systematic review and meta-analysis of the efficacy and safety of chromium supplementation in diabetes. J Clin Pharm Ther 39:292–306

    Article  CAS  PubMed  Google Scholar 

  21. Sharma S, Agrawal RP, Choudhary M, Jain S, Goyal S, Agarwal V (2011) Beneficial effect of chromium supplementation on glucose, HbA1C and lipid variables in individuals with newly onset type-2 diabetes. J Trace Elem Med Biol 25:149–153

    Article  CAS  PubMed  Google Scholar 

  22. Liu L, Jin W, Lv JP (2010) Oral administration of the high-chromium yeast improve blood plasma variables and pancreatic islet tissue in diabetic mice. Biol Trace Elem Res 138:250–264

    Article  CAS  PubMed  Google Scholar 

  23. Morya K, Vachhrajani KD (2014) Impairment of renal structure and function following heterogeneous chemical mixture exposure in rats. Indian J Exp Biol 52:332–343

    CAS  PubMed  Google Scholar 

  24. Castro MP, de Moraes FR, Fujimoto RY, da Cruz C, Belo MAD, de Moraes JRE (2014) Acute toxicity by water containing hexavalent or trivalent chromium in native Brazilian fish, Piaractus mesopotamicus: anatomopathological alterations and mortality. B Environ Contam Toxicol 92:213–219

    Article  CAS  Google Scholar 

  25. Mozaffari MS, Baban B, Abdelsayed R, Liu JY, Wimborne H, Rodriguez N, Abebe W (2012) Renal and glycemic effects of high-dose chromium picolinate in db/db mice: assessment of DNA damage. J Nutr Biochem 23:977–985

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  26. Tan GY, Zheng SS, Zhang MH, Feng JH, Xie P, Bi JM (2008) Study of oxidative damage in growing-finishing pigs with continuous excess dietary chromium picolinate intake. Biol Trace Elem Res 126:129–140

    Article  CAS  PubMed  Google Scholar 

  27. Andersson MA, Grawe KVP, Karlsson OM, Abramsson-Zetterberg LAG, Hellman BE (2007) Evaluation of the potential genotoxicity of chromium picolinate in mammalian cells in vivo and in vitro. Food Chem Toxicol 45:1097–1106

    Article  CAS  PubMed  Google Scholar 

  28. Bailey MM, Boohaker JG, Sawyer RD, Behling JE, Rasco JF, Jernigan JJ, Hood RD, Vincent JB (2006) Exposure of pregnant mice to chromium picolinate results in skeletal defects in their offspring. Birth Defects Res B 77:244–249

    Article  CAS  Google Scholar 

  29. Mahmoud AA, Karam SH, Abdel-Wahhab MA (2006) Chromium-picolinate induced ocular changes: protective role of ascorbic acid. Toxicology 226:143–151

    Article  CAS  PubMed  Google Scholar 

  30. China’s Ministry of Health (2003) Procedures for toxicological assessment of food: Procedure and methods of food safety toxicological assessment. GB15193–2003

  31. Yoshikawa Y, Kishimoto Y, Tagami H, Kanahori S (2013) Assessment of the safety of hydrogenated resistant maltodextrin: reverse mutation assay, acute and 90-day subchronic repeated oral toxicity in rats, and acute no-effect level for diarrhea in humans. J Toxicol Sci 38:459–470

    Article  CAS  PubMed  Google Scholar 

  32. Feist B, Mikula B, Pytlakowska K, Puzio B, Buhl F (2008) Determination of heavy metals by icp-oes and f-aas after preconcentration with 2, 2′-bipyridyl and erythrosine. J Hazard Mater 152:1122–1129

    Article  CAS  PubMed  Google Scholar 

  33. Enomoto T, Ishibashi T, Tokuda K, Ishiyama T, Toma S, Ito A (2008) Lurasidone reverses MK-801-induced impairment of learning and memory in the Morris water maze and radial-arm maze tests in rats. Behav Brain Res 186:197–207

    Article  CAS  PubMed  Google Scholar 

  34. Huang S, Peng WF, Jiang XH, Shao K, Xia LL, Tang YB, Qiu JY (2014) The effect of chromium picolinate supplementation on the pancreas and macroangiopathy in type II diabetes mellitus rats. J Diabetes Res 2014:1–8

    Google Scholar 

  35. Waylan AT, Quinn PRO, Goodband RD, Unruh JA, Nelssen JL, Woodworth JC, Tokach MD (2003) Effects of dietary additions of modified tall oil, chromium nicotinate, and L-carnitine on growth performance, carcass characteristics, and bacon characteristics of growing-finishing pigs. Can J Anim Sci 83:459–467

    Article  CAS  Google Scholar 

  36. Hepburn DDD, Xiao J, Bindom S, Vincent JB, O’Donnell J (2003) Nutritional supplement chromium picolinate causes sterility and lethal mutations in Drosophila melanogaster. Abstr Pap Am Chem Soc 225:U31–U31

    Google Scholar 

  37. Stallings DM, Hepburn DDD, Hannah M, Vincent JB, O’Donnell J (2006) Nutritional supplement chromium picolinate generates chromosomal aberrations and impedes progeny development in Drosophila melanogaster. Mutat Res Genet Tox Environ Mutagen 610:101–113

    Article  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported financially by Specialized Research Fund for the Natural Science Foundation of China (31271850), Graduate innovative projects in Jiangsu University (CXLX13_685). We also appreciate Dr. Samuel Jerry Cobbina for language polishing.

Conflict of Interest

The authors declare that there are no competing interests.

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Liuqing Yang or Xiangyang Wu.

Additional information

Weiwei Feng and Huiyu Wu contributed equally to this work.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Feng, W., Wu, H., Li, Q. et al. Evaluation of 90-day Repeated Dose Oral Toxicity, Glycometabolism, Learning and Memory Ability, and Related Enzyme of Chromium Malate Supplementation in Sprague-Dawley Rats. Biol Trace Elem Res 168, 181–195 (2015). https://doi.org/10.1007/s12011-015-0341-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12011-015-0341-4

Keywords

Navigation