Cytotoxic Effects of 4-methylimidazole on Bone Marrow Mesenchymal Stem Cells in Vitro

Overview

Journal Am J Transl Res

Specialty General Medicine

Date 2015 Dec 23

PMID 26692921

Citations 4

Authors

Fan Bu

Tao Li

Yanling Ding

Lingxian Sun

Tao Tu

Fangfang Zhou

Wenkai Qi

Xinyi Jiang

Jie Fang

Jiabo Hu

Wei Zhu

Xiaochun Sun

Affiliations

Soon will be listed here.

Abstract

4-Methylimidazole (4-MI) is found in a great number of food products. The National Toxicology Program (NTP) revealed that 4-MI is carcinogenic and can also cause anemia and weight loss. Mesenchymal stem cells (MSCs) are able to support hematopoiesis and migrate to the site of tumors. To investigate whether 4-MI has an impact on MSCs, we have measured the ability of cell (osteoblast, adipocyte) proliferation, apoptosis, cell cycle, gene expression, migration and differentiation between control group and the 4-MI group. The results showed that higher concentrations of 4-MI (≥150 μg/ml) had significant effects on BMSCs viability while lower concentrations (≤100 μg/ml) had no significant effects on cell proliferation, apoptosis, migration, differentiation, and expression of relevant marker genes of hematopoietic cytokines, including TPO, SCF, VEGF and FLt3. The results also indicated that 4-MI (≤100 μg/ml) may have no significant effect on the biological characteristics of MSCs. Low concentration of 4-MI in foods and beverages have no toxic effect on BMSCs. The anemia and weight loss of animals caused by 4-MI may not be due to its effect on BMSCs.

Citing Articles

Drosophila Toxicogenomics: genetic variation and sexual dimorphism in susceptibility to 4-Methylimidazole.

Collins K, Howansky E, Macon-Foley S, Adonay M, Shankar V, Lyman R Hum Genomics. 2024; 18(1):119.

PMID: 39497218 PMC: 11533318. DOI: 10.1186/s40246-024-00689-3.

Mesenchymal stem cell-derived extracellular vesicles promote nerve regeneration after sciatic nerve crush injury in rats.

Ma Y, Ge S, Zhang J, Zhou D, Li L, Wang X Int J Clin Exp Pathol. 2020; 10(9):10032-10039.

PMID: 31966893 PMC: 6965921.

Mesenchymal stem cell-derived extracellular vesicles promote apoptosis in RSC96 Schwann cells through the activation of the ERK pathway.

Zhou D, Zhai W, Zhang M Int J Clin Exp Pathol. 2020; 11(11):5157-5170.

PMID: 31949596 PMC: 6963017.

BMSC paracrine activity attenuates interleukin-1β-induced inflammation and apoptosis in rat AF cells via inhibiting relative NF-κB signaling and the mitochondrial pathway.

Hu J, Yan Q, Shi C, Tian Y, Cao P, Yuan W Am J Transl Res. 2017; 9(1):79-89.

PMID: 28123635 PMC: 5250705.

References

Haseman J . Evaluating consistency in the interpretation of NTP rodent cancer bioassays: an examination of mouse lung tumor effects in the 4-MEI study. Regul Toxicol Pharmacol. 2013; 66(1):109-15. DOI: 10.1016/j.yrtph.2013.03.009. View

Hengel M, Shibamoto T . Carcinogenic 4(5)-methylimidazole found in beverages, sauces, and caramel colors: chemical properties, analysis, and biological activities. J Agric Food Chem. 2013; 61(4):780-9. DOI: 10.1021/jf304855u. View

Moon J, Shibamoto T . Formation of carcinogenic 4(5)-methylimidazole in Maillard reaction systems. J Agric Food Chem. 2010; 59(2):615-8. DOI: 10.1021/jf104098a. View

Chan P, Hill G, Hills G, Kissling G, Nyska A . Toxicity and carcinogenicity studies of 4-methylimidazole in F344/N rats and B6C3F1 mice. Arch Toxicol. 2007; 82(1):45-53. PMC: 2366200. DOI: 10.1007/s00204-007-0222-5. View

Yamaguchi H, Masuda T . Determination of 4(5)-methylimidazole in soy sauce and other foods by LC-MS/MS after solid-phase extraction. J Agric Food Chem. 2011; 59(18):9770-5. DOI: 10.1021/jf201736c. View

. Toxicology and carcinogenesis studies of 4-methylimidazole (Cas No. 822-36-6) in F344/N rats and B6C3F1 mice (feed studies). Natl Toxicol Program Tech Rep Ser. 2007; (535):1-274. View

Gu W, Helms V . Different protonation equilibria of 4-methylimidazole and acetic acid. Chemphyschem. 2007; 8(17):2445-51. DOI: 10.1002/cphc.200700442. View

Krishna K, Goel S, Krishna G . SAR genotoxicity and tumorigenicity predictions for 2-MI and 4-MI using multiple SAR software. Toxicol Mech Methods. 2014; 24(4):284-93. DOI: 10.3109/15376516.2014.881946. View

Chan P . NTP technical report on the toxicity studies of 2- and 4-Methylimidazole (CAS No. 693-98-1 and 822-36-6) administered in feed to F344/N rats and B6C3F1 mice. Toxic Rep Ser. 2004; (67):1-G12. View

10.

Kim T, Kim S, Shin Y, Kim J, Lee S, Kim J . Determination of 4-Methylimidazole and 2-Acetyl-4()- tetrahydroxybutylimidazole in Caramel Color and Processed Foods by LC-MS/MS. Prev Nutr Food Sci. 2014; 18(4):263-8. PMC: 3925216. DOI: 10.3746/pnf.2013.18.4.263. View

11.

Dwyer R, Khan S, Barry F, OBrien T, Kerin M . Advances in mesenchymal stem cell-mediated gene therapy for cancer. Stem Cell Res Ther. 2010; 1(3):25. PMC: 2941117. DOI: 10.1186/scrt25. View

12.

Sivertsen T, Langseth W, Mo E, Ingebrigtsen K . Further arguments against 4-methylimidazole as causal factor in ammoniated forage toxicosis: experimental seed-hay poisoning in young lambs. Acta Vet Scand. 1993; 34(2):227-30. PMC: 8112505. View

13.

Xu H, Qian H, Zhu W, Zhang X, Yan Y, Mao F . Mesenchymal stem cells relieve fibrosis of Schistosoma japonicum-induced mouse liver injury. Exp Biol Med (Maywood). 2012; 237(5):585-92. DOI: 10.1258/ebm.2012.011362. View

14.

Jiang Y, Jahagirdar B, Reinhardt R, Schwartz R, Keene C, Ortiz-Gonzalez X . Pluripotency of mesenchymal stem cells derived from adult marrow. Nature. 2002; 418(6893):41-9. DOI: 10.1038/nature00870. View

15.

Weissman I . Stem cells: units of development, units of regeneration, and units in evolution. Cell. 2000; 100(1):157-68. DOI: 10.1016/s0092-8674(00)81692-x. View

16.

Wang X, Zhao T, Huang W, Wang T, Qian J, Xu M . Hsp20-engineered mesenchymal stem cells are resistant to oxidative stress via enhanced activation of Akt and increased secretion of growth factors. Stem Cells. 2009; 27(12):3021-31. PMC: 2806498. DOI: 10.1002/stem.230. View

17.

Spaeth E, Klopp A, Dembinski J, Andreeff M, Marini F . Inflammation and tumor microenvironments: defining the migratory itinerary of mesenchymal stem cells. Gene Ther. 2008; 15(10):730-8. DOI: 10.1038/gt.2008.39. View

18.

Silver J, Marsh P, Symons M, Svistunenko D, Frampton C, Fern G . Crystal structure of bis(4-methylimidazole)tetraphenylporphyrinatoiron(III) chloride and related compounds. Correlation of ground state with Fe-N bond lengths. Inorg Chem. 2001; 39(13):2874-81. DOI: 10.1021/ic990848s. View

19.

Fairbrother T, Kerr L, ESSIG H . Effects of 4-methylimidazole in young calves. Vet Hum Toxicol. 1987; 29(4):312-5. View

20.

Dazzi F, Ramasamy R, Glennie S, Jones S, Roberts I . The role of mesenchymal stem cells in haemopoiesis. Blood Rev. 2005; 20(3):161-71. DOI: 10.1016/j.blre.2005.11.002. View