Skip to main content
SpringerLink
Log in

Influence of Chronic Toxicity, Lipid Metabolism, Learning and Memory Ability, and Related Enzyme in Sprague-Dawley Rats by Long-Term Chromium Malate Supplementation

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

Abstract

In our previous study, chromium malate is beneficial for type 2 diabetic rats in control glycometabolism and lipid metabolism. The present study was designed to observe the chronic toxicity, lipid metabolism, learning and memory ability, and related enzymes of chromium malate in rats during the year. The results showed that pathological, toxic, feces, and urine of chromium malate (at daily doses of 10.0, 15.0, and 20.0 μg Cr/kg bm) did not change measurably. Chromium malate (at daily doses of 15.0 and 20.0 μg Cr/kg bm) could significantly reduce the levels of total cholesterol (TC), LDL, and triglyceride (TG), and increase the level of HDL in male rats compared to control group and chromium picolinate group. Significant escalating trends of the escape latency and swimming speed (Morris water maze test), and the original platform quadrant stops, residence time, and swimming speed (Space exploration test) in male rats of chromium malate groups were obtained. The SOD, GSH-Px, and TChE activities of chromium malate (at daily doses of 15.0 and 20.0 μg Cr/kg bm) were enhanced significantly in male rats compared with those of the normal control group and chromium picolinate group. Glycometabolism and related enzymes had no significant changes compared to normal control group and chromium picolinate group. These results indicated that long-term chromium malate supplementation did not cause measurable toxicity at daily doses of 10.0, 15.0, and 20.0 μg Cr/kg bm and could improve dyslipidemia and learning and memory deficits.

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

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

Similar content being viewed by others

References

  1. Reijonen I, Hartikainen H (2016) Oxidation mechanisms and chemical bioavailability of chromium in agricultural soil—pH as the master variable. Appl Geochem 74:84–93

    Article  CAS  Google Scholar 

  2. Ganguly R, Sahu S, Ohanyan V, Haney R, Chavez RJ, Shah S, Yalamanchili S, Raman P (2017) Oral chromium picolinate impedes hyperglycemia-induced atherosclerosis and inhibits proatherogenic protein TSP-1 expression in STZ-induced type 1 diabetic ApoE(−/−) mice. Sci Rep 7. https://doi.org/10.1038/srep45279

  3. Panchal SK, Wanyonyi S, Brown L (2017) Selenium, vanadium, and chromium as micronutrients to improve metabolic syndrome. Curr Hypertens Rep 19:10. https://doi.org/10.1007/s11906-017-0701-x

    Article  CAS  PubMed  Google Scholar 

  4. Saeed AA, Sandhu MA, Khilji MS, Yousaf MS, Rehman HU, Tanvir ZI, Ahmad T (2017) Effects of dietary chromium supplementation on muscle and bone mineral interaction in broiler chicken. J Trace Elem Med Biol 42:25–29

    Article  CAS  PubMed  Google Scholar 

  5. Hu LY, Yang FK, Lu L, Dai W (2017) Arsenic-induced sumoylation of Mus81 is involved in regulating genomic stability. Cell Cycle 16:802–811

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Heitland P, Blohm M, Breuer C, Brinkert F, Achilles EG, Pukite I, Koster HD (2017) Application of ICP-MS and HPLC-ICP-MS for diagnosis and therapy of a severe intoxication with hexavalent chromium and inorganic arsenic. J Trace Elem Med Biol 41:36–40

    Article  CAS  PubMed  Google Scholar 

  7. Thompson CM, Seiter J, Chappell MA, Tappero RV, Proctor DM, Suh M, Wolf JC, Haws LC, Vitale R, Mittal L, Kirman CR, Hays SM, Harris MA (2015) Synchrotron-based imaging of chromium and γ-H2AX immunostaining in the duodenum following repeated exposure to Cr(VI) in drinking water. Toxicol Sci 143:16–25

    Article  CAS  PubMed  Google Scholar 

  8. Warnakulasuriya SN, Ziaullah, Rupasinghe HPV (2016) Novel long chain fatty acid derivatives of quercetin-3-O-glucoside reduce cytotoxicity induced by cigarette smoke toxicants in human fetal lung fibroblasts. Eur J Pharmacol 781:128–138

    Article  CAS  PubMed  Google Scholar 

  9. Liu M, Liu Y, Cheng Z, Liu J, Chai T (2015) Effects of chromic chloride on chick embryo fibroblast viability. Toxicol Rep 2:555–562

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Iijima S, Matsumoto N, Lu CC (1983) Transfer of chromic chloride to embryonic mice and changes in the embryonic mouse neuroepithelium. Toxicology 26:257–265

    Article  CAS  PubMed  Google Scholar 

  11. Hepburn DDD, Marcel Burney J, Woski SA, Vincent JB (2003) The nutritional supplement chromium picolinate generates oxidative DNA damage and peroxidized lipids in vivo. Polyhedron 22:455–463

    Article  CAS  Google Scholar 

  12. Whittaker P, San RHC, Clarke JJ, Seifried HE, Dunkel VC (2005) Mutagenicity of chromium picolinate and its components in Salmonella typhimurium and L5178Y mouse lymphoma cells. Food Chem Toxicol 43:1619–1625

    Article  CAS  PubMed  Google Scholar 

  13. Feng WW, Zhao T, Mao GH, Wang W, Feng Y, Li F, Zheng DH, Wu HY, Jin D, Yang LQ, Wu XY (2015) Type 2 diabetic rats on diet supplemented with chromium malate show improved glycometabolism, glycometabolism-related enzyme levels and lipid metabolism. PLoS One 10

  14. Refat MS, El-Megharbel SM, Hussien MA, Hamza RZ, Al-Omar MA, Naglah AM, Afifi WM, Kobeasy MI (2017) Spectroscopic, structural characterizations and antioxidant capacity of the chromium (III) niacinamide compound as a diabetes mellitus drug model. Spectrochim Acta A 173:122–131

    Article  CAS  Google Scholar 

  15. Wang S, Wang J, Zhang XN, Hu LL, Fang ZJ, Huang ZW, Shi P (2016) Trivalent chromium alleviates oleic acid induced steatosis in SMMC-7721 cells by decreasing fatty acid uptake and triglyceride synthesis. Biomentals 29:881–892

    Article  CAS  Google Scholar 

  16. World Health Organization (2016) Obesity and overweight. Fact sheet No 311. Accessed Sept 2016

  17. Emdin CA, Khera AV, Natarajan P, Klarin D, Zekavat SM, Hsiao AJ, Kathiresan S (2017) Genetic association of waist-to-hip ratio with cardiometabolic traits, type 2 diabetes, and coronary heart disease. JAMA J Am Med Assoc 317:626–634

    Article  Google Scholar 

  18. Kim N, Nakamura H, Masaki H, Kumasawa K, Hirano K, Kimura T (2017) Effect of lipid metabolism on male fertility. Biochem Biophys Res Commun 485:686–692

    Article  CAS  PubMed  Google Scholar 

  19. Roehrig M, Masheb RM, White MA, Grilo CM (2009) Dieting frequency in obese patients with binge eating disorder: behavioral and metabolic correlates. Obesity 17:689–697

    Article  PubMed  Google Scholar 

  20. Kiasalari Z, Heydarifard R, Khalili M, Afshin-Majd S, Baluchnejadmojarad T, Zahedi E, Sanaierad A, Roghani M (2017) Ellagic acid ameliorates learning and memory deficits in a rat model of Alzheimer’s disease: an exploration of underlying mechanisms. Psychopharmacology 234:1841–1852

    Article  CAS  PubMed  Google Scholar 

  21. Yu F, Chen J (2014) Healthcare product useful in pharmaceutical for treating neurasthenia and enhancing learning and memory ability of people, comprises oxypeucedanin and auxiliary materials. Derwent Innovations Index CN103948036-A; CN103948036-B

  22. Klein C, Jonas W, Iggena D, Empl L, Rivalan M, Wiedmer P, Spranger J, Hellweg R, Winter Y, Steiner B (2016) Exercise prevents high-fat diet-induced impairment of flexible memory expression in the water maze and modulates adult hippocampal neurogenesis in mice. Neurobiol Learn Mem 131:26–35

    Article  CAS  PubMed  Google Scholar 

  23. Fazelian S, Rouhani MH, Bank SS, Amani R (2017) Chromium supplementation and polycystic ovary syndrome: a systematic review and meta-analysis. J Trace Elem Med Biol 42:92–96

    Article  CAS  PubMed  Google Scholar 

  24. Li CY, Feng FH, Xiong XL, Li R, Chen N (2017) Exercise coupled with dietary restriction reduces oxidative stress in male adolescents with obesity. J Sport Sci 35:663–668

    Article  Google Scholar 

  25. Cheng J, Chen L, Han S, Qin L, Chen N, Wan Z (2016) Treadmill running and rutin reverse high fat diet induced cognitive impairment in diet induced obese mice. J Nutr Health Aging 20:503–508

    Article  CAS  PubMed  Google Scholar 

  26. 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 

  27. Smart M, Brown S, Tannehill H, Lockart M, Bowman MK, Vincent JB (2018) The identity of “chromium malate”. Biol Trace Elem Res 181:369–377

    Article  CAS  PubMed  Google Scholar 

  28. 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 

  29. Sereshti H, Khojeh V, Samadi S (2011) Optimization of dispersive liquid–liquid microextraction coupled with inductively coupled plasma-optical emission spectrometry with the aid of experimental design for simultaneous determination of heavy metals in natural waters. Talanta 83:885–890

    Article  CAS  PubMed  Google Scholar 

  30. Stout MD, Nyska A, Collins BJ, Witt KL, Kissling GE, Malarkey DE, Hooth MJ (2009) Chronic toxicity and carcinogenicity studies of chromium picolinate monohydrate administered in feed to F344/N rats and B6C3F1 mice for 2 years. Food Chem Toxicol 47:729–733

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Feng WW, Wu HY, Li Q, Zhou ZX, Chen Y, Zhao T, Feng Y, Mao GH, Li F, Yang LQ, Wu XY (2015) 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

    Article  CAS  PubMed  Google Scholar 

  32. Feng WW, Zhang WJ, Zhao T, Mao GH, Wang W, Wu XS, Zhou ZX, Huang J, Bao YT, Yang LQ, Wu XY (2015) Evaluation of the reproductive toxicity, glycometabolism, glycometabolism-related enzyme levels and lipid metabolism of chromium malate supplementation in Sprague-Dawley rats. Biol Trace Elem Res 168:150–168

    Article  CAS  PubMed  Google Scholar 

  33. Shara M, Kincaid AE, Limpach AL, Sandstrom R, Barrett L, Norton N, Bramble JD, Yasmin T, Tran J, Chatterjee A, Bagchi M, Bagchi D (2007) Long-term safety evaluation of a novel oxygen-coordinated niacin-bound chromium (III) complex. J Inorg Biochem 101:1059–1069

    Article  CAS  PubMed  Google Scholar 

  34. Sreejayan N, Dong F, Kandadi MR, Yang XP, Ren J (2008) Chromium alleviates glucose intolerance, insulin resistance, and hepatic ER stress in obese mice. Obesity 16:1331–1337

    Article  CAS  PubMed  Google Scholar 

  35. Yang XP, Li SY, Dong F, Ren J, Sreejayan N (2006) Insulin-sensitizing and cholesterol-lowering effects of chromium (D-Phenylalanine)(3). J Inorg Biochem 100:1187–1193

    Article  CAS  PubMed  Google Scholar 

  36. Atila G, Yuce A (2016) Effects of the Trigonella foenum-graecum L. seed extract and chromium picolinate supplementation in streptozotocin induced diabetes in rats. Indian J Tradit Knowl 15:447–452

    Google Scholar 

  37. Sahin K, Tuzcu M, Orhan C, Agca CA, Sahin N, Guvenc M, Krejpcio Z, Staniek H, Hayirli A (2011) The effects of chromium complex and level on glucose metabolism and memory acquisition in rats fed high-fat diet. Biol Trace Elem Res 143:1018–1030

    Article  CAS  PubMed  Google Scholar 

  38. Cheke LG, Bonnici HM, Clayton NS, Simons JS (2017) Obesity and insulin resistance are associated with reduced activity in core memory regions of the brain. Neuropsychologia 96:137–149

    Article  PubMed  PubMed Central  Google Scholar 

  39. Cordner ZA, Tamashiro KLK (2015) Effects of high-fat diet exposure on learning & memory. Physiol Behav 152:363–371

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Funding

This work was supported financially by Specialized Research Fund for the Natural Science Foundation of China (31271850), Research Foundation for Advanced Talents of Jiangsu University (15JDG146).

Author information

Authors and Affiliations

  1. School of the Environment and Safety Engineering, Jiangsu University, Zhenjiang, Jiangsu, China

    Weiwei Feng, Yao Chen, Guanghua Mao & Xiangyang Wu

  2. Institute of Environmental health and Ecological Security, Jiangsu University, Zhenjiang, Jiangsu, China

    Weiwei Feng & Xiangyang Wu

  3. School of Food and Biological Engineering, Jiangsu University, Zhenjiang, Jiangsu, China

    Qian Li, Wei Wang & Weijie Zhang

  4. School of Chemistry and Chemical Engineering, Jiangsu University, Zhenjiang, Jiangsu, China

    Ting Zhao & Liuqing Yang

Authors
  1. Weiwei Feng
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Qian Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Wei Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yao Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Weijie Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Ting Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Guanghua Mao
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Xiangyang Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Liuqing Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Liuqing Yang.

Ethics declarations

Conflict of Interest

The authors declare that they have no competing interests.

Additional information

Highlights

• Chromium malate (10.0, 15.0, and 20.0 μg Cr/kg bm) did not cause measurable toxicity.

• Chromium malate can improve lipid metabolism.

• Chromium malate can improve learning and memory ability.

• Chromium malate can increase the related enzyme (SOD, GSH-Px, and TChE) activities.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Feng, W., Li, Q., Wang, W. et al. Influence of Chronic Toxicity, Lipid Metabolism, Learning and Memory Ability, and Related Enzyme in Sprague-Dawley Rats by Long-Term Chromium Malate Supplementation. Biol Trace Elem Res 187, 243–257 (2019). https://doi.org/10.1007/s12011-018-1377-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12011-018-1377-z

Keywords

Search

Navigation