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Maternal curcumin exposure causes fetal gross morphological anomalies and skeletal malformations in mouse

By: Julliane Monique A. Tagala, Alicia Magdalene Q. Biteng, Jocelyn R. Rafanan, Mayer L. Calma

Key Words: Curcumin, Turmeric, Teratogenicity, Gross morphological anomalies, Skeletal malformations.

Int. J. Biosci. 16(2), 382-393, February 2020.

DOI: http://dx.doi.org/10.12692/ijb/16.2.382-393

Certification: ijb 2020 0364 [Generate Certificate]

Abstract

Curcumin is a phenolic compound extracted from the rhizome of turmeric (Curcuma longa L.). Although declared as safe for human consumption, curcumin has been found to be embryotoxic in some organisms indicating its potential as a teratogen. In this study, the teratogenic effect of maternal curcumin exposure in mouse fetuses was evaluated. Three experimental groups of pregnant mice were treated with 1.05, 1.52, and 2.0 mg/g body weight/day 95% curcumin, respectively, from gestation day (GD) 6 to 15. A fourth group without curcumin exposure served as a control. At GD18, the mice were sacrificed and the total number of implanted embryos including resorbed, dead, and live fetuses were counted for litter analysis. Extracted fetuses were also analyzed for gross morphological anomalies and subsequently have undergone alizarin staining for the visualization of skeletal malformations. Results showed an increased resorption rate in the 2.0 mg/g treatment (p<0.001). There is also a reduction of fetal weight (p<0.001) and crown-rump length (p<0.001) in a dose-dependent manner. Gross morphological analysis shows cranio-facial malformations such as flattened nose bridge (p<0.05) and micrognathia (p<0.05) in 2.0 mg/g treatment. Skeletal malformations such as large anterior fontanelle (p<0.001), misaligned ossification centers in the sternum (p<0.001), and delayed ossification in the forepaws, hind paws, and caudal vertebrae (p<0.001) were also observed at 2.0 mg/g treatment. Meanwhile, the presence of supernumerary ribs is not statistically different in the four groups. The results indicate that curcumin is teratogenic in mouse fetuses due to observed gross morphological anomalies and skeletal malformations.

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Maternal curcumin exposure causes fetal gross morphological anomalies and skeletal malformations in mouse

Additives EPoF, Nutrient Sources added to F. 2010. Scientific Opinion on the re-evaluation of curcumin (E 100) as a food additive. EFSA Journal 8, 1679.

Alafiatayo AA, Lai KS, Syahida A, Mahmood M, Shaharuddin NA. 2019. Phytochemical Evaluation, Embryotoxicity, and Teratogenic Effects of Curcuma longa Extract on Zebrafish (Danio rerio). Evidence-Based Complementary and Alternative Medicine 2019.

https://doi.org/10.1155/2019/3807207

Bolon B. 2015. Pathology of the Developing Mouse: A Systematic Approach. CRC Press.

Cao J, Jia L, Zhou H-M, Liu Y, Zhong LF. 2006. Mitochondrial and nuclear DNA damage induced by curcumin in human hepatoma G2 cells. Toxicological Sciences 91, 476-483.

https://doi.org/10.1093/toxsci/kfj153

Catela C, Bilbao-Cortes D, Slonimsky E, Kratsios P, Rosenthal N, te Welscher P. 2009. Multiple congenital malformations of Wolf-Hirschhorn syndrome are recapitulated in Fgfrl1 null mice. Disease Models & Mechanisms 2, 283-294. https://doi.org/10.1242/dmm.002287

Chang MT, Tsai TR, Lee CY, Wei YS, Chen YJ, Chen CR, Tzen JT. 2013. Elevating bioavailability of curcumin via encapsulation with a novel formulation of artificial oil bodies. Journal of Agricultural and Food Chemistry 61, 9666-9671.

https://doi.org/10.1021/jf4019195

Chen CC, Chan WH. 2012. Injurious effects of curcumin on maturation of mouse oocytes, fertilization and fetal development via apoptosis. International Journal of Molecular Sciences 13, 4655-4672.

https://doi.org/10.3390/ijms13044655

Chen CC, Hsieh MS, Hsuuw YD, Huang FJ, Chan WH. 2010. Hazardous effects of curcumin on mouse embryonic development through a mitochondria-dependent apoptotic signaling pathway. International Journal of Molecular Sciences 11, 2839-2855.

https://doi.org/10.3390/ijms11082839

Chernoff N, Rogers JM. 2004. Supernumerary ribs in developmental toxicity bioassays and in human populations: incidence and biological significance. Journal of Toxicology and Environmental Health, Part B 7, 437-449.

https://doi.org/10.1080/10937400490512447

Dadhaniya P, Patel C, Muchhara J, Bhadja N, Mathuria N, Vachhani K, Soni MG. 2011. Safety assessment of a solid lipid curcumin particle preparation: acute and subchronic toxicity studies. Food and Chemical Toxicology 49, 1834-1842.

https://doi.org/10.1016/j.fct.2011.05.001

Dance-Barnes ST, Kock ND, Moore JE, Lin EY, Mosley LJ, D’Agostino Jr RB, McCoy TP, Townsend AJ, Miller MS. 2010. Lung tumor promotion by curcumin. Carcinogenesis 31, 1903.

https://doi.org/10.1093/carcin/bgp082

de Araújo Costa G, Galvão TC, Bacchi AD, Moreira EG, Salles MJS. 2016. Investigation of possible teratogenic effects in the offspring of mice exposed to methylphenidate during pregnancy. Reproductive Biomedicine Online 32, 170-177.

https://doi.org/10.1016/j.rbmo.2015.11.016

Dewar AM, Clark RA, Singer AJ, Frame MD. 2011. Curcumin mediates both dilation and constriction of peripheral arterioles via adrenergic receptors. Journal of Investigative Dermatology 131, 1754-1760.

https://doi.org/10.1038/jid.2011.96

Ejaz A, Wu D, Kwan P, Meydani M. 2009. Curcumin inhibits adipogenesis in 3T3-L1 adipocytes and angiogenesis and obesity in C57/BL mice. The Journal of Nutrition 139, 919-925.

https://doi.org/10.3945/jn.108.100966

Etemad L, Mohammad A, Mohammadpour AH, Mashhadi NV, Moallem SA. 2013. Teratogenic effects of pregabalin in mice. Iranian Journal of Basic Medical Sciences 16, 1065.

Ganiger S, Malleshappa HN, Krishnappa H, Rajashekhar G, Ramakrishna Rao V, Sullivan F. 2007. A two generation reproductive toxicity study with curcumin, turmeric yellow, in Wistar rats. Food and Chemical Toxicology 45, 64-69.

https://doi.org/10.1016/j.fct.2006.07.016

Gholami M, Moallem SA, Afshar M, Amoueian S, Etemad L, Karimi G. 2016. Teratogenic effects of silymarin on mouse fetuses. Avicenna Journal of Phytomedicine 6, 542.

Goodpasture C, Arrighi F. 1976. Effects of food seasonings on the cell cycle and chromosome morphology of mammalian cells in vitro with special reference to turmeric. Food and Cosmetics Toxicology 14, 9-14.

https://doi.org/10.1016/S0015-6264(76)80356-2

Gordon CT, Weaver KN, Zechi-Ceide RM, Madsen EC, Tavares AL, Oufadem M, Kurihara Y, Adameyko I, Picard A, Breton S. 2015. Mutations in the endothelin receptor type A cause mandibulofacial dysostosis with alopecia. The American Journal of Human Genetics 96, 519-531. https://doi.org/10.1016/j.ajhg.2015.01.015

Guo YZ, He P, Feng AM. 2017. Effect of curcumin on expressions of NF-κBp65, TNF-α and IL-8 in placental tissue of premature birth of infected mice. Asian Pacific Journal of Tropical Medicine 10, 175-178.

https://doi.org/10.1016/j.apjtm.2017.01.004

He B, Hu M, Yang XT, Lu YQ, Liu JX, Chen P, Shen ZQ. 2013. Effects of geraniin on osteoclastic bone resorption and matrix metalloproteinase-9 expression. Bioorganic & Medicinal Chemistry Letters 23, 630-634.

https://doi.org/10.1016/j.bmcl.2012.12.005

Heyne GW, Plisch EH, Melberg CG, Sandgren EP, Peter JA, Lipinski RJ. 2015. A Simple and Reliable Method for Early Pregnancy Detection in Inbred Mice. Journal of the American Association for Laboratory Animal Science : JAALAS 54, 368-371.

Huang FJ, Lan KC, Kang HY, Liu YC, Hsuuw YD, Chan WH, Huang KE. 2013. Effect of curcumin on in vitro early post-implantation stages of mouse embryo development. European Journal of Obstetrics & Gynecology and Reproductive Biology 166, 47-51.

https://doi.org/10.1016/j.ejogrb.2012.09.010

Li G, Bu J, Zhu Y, Xiao X, Liang Z, Zhang R. 2015. Curcumin improves bone microarchitecture in glucocorticoid-induced secondary osteoporosis mice through the activation of microRNA-365 via regulating MMP-9. International Journal of Clinical and Experimental Pathology 8, 15684.

Lin HP, Kuo LK, Chuu CP. 2012. Combined treatment of curcumin and small molecule inhibitors suppresses proliferation of A549 and H1299 human non‐small‐cell lung cancer cells. Phytotherapy Research 26, 122-126.

https://doi.org/10.1002/ptr.3523

Mahmood K, Zia KM, Zuber M, Salman M, Anjum MN. 2015. Recent developments in curcumin and curcumin based polymeric materials for biomedical applications: A review. International Journal of Biological Macromolecules 81, 877-890.

https://doi.org/10.1016/j.ijbiomac.2015.09.026

Marsden E, Leroy M. 2013. Teratology studies in the mouse. Pages 111-123. Teratogenicity Testing,  Springer.

Mu J, Slevin JC, Qu D, McCormick S, Adamson SL. 2008. In vivo quantification of embryonic and placental growth during gestation in mice using micro-ultrasound. Reproductive Biology and Endocrinology 6, 34.

https://doi.org/10.1186/1477-7827-6-34

Nelson KM, Dahlin JL, Bisson J, Graham J, Pauli GF, Walters MA. 2017. The Essential Medicinal Chemistry of Curcumin. Journal of Medicinal Chemistry 60, 1620-1637.

https://doi.org/10.1021/acs.jmedchem.6b00975

Program NT. 1993. NTP Toxicology and Carcinogenesis Studies of Turmeric Oleoresin (CAS No. 8024-37-1)(Major Component 79%-85% Curcumin, CAS No. 458-37-7) in F344/N Rats and B6C3F1 Mice (Feed Studies). National Toxicology Program Technical Report Series 427, 1.

Reynaud L, Jocteur-Monrozier A. 2013. Skeletal examination by alizarin staining. Pages 201-213. Teratogenicity Testing,  Springer.

Sagar SM, Yance D, Wong R. 2006. Natural health products that inhibit angiogenesis: a potential source for investigational new agents to treat cancer—part 1. Current Oncology 13, 14.

Shen G, Xu C, Hu R, Jain MR, Gopalkrishnan A, Nair S, Huang MT, Chan JY, Kong ANT. 2006. Modulation of nuclear factor E2-related factor 2–mediated gene expression in mice liver and small intestine by cancer chemopreventive agent curcumin. Molecular Cancer Therapeutics 5, 39-51.

https://doi.org/10.1158/1535-7163.MCT-05-0293

Shin HJ, Cho YM, Shin HJ, Kim HD, Choi KM, Kim MG, Shin HD, Chung MW. 2017. Comparison of commonly used ICR stocks and the characterization of Korl: ICR. Laboratory Animal Research 33, 8-14.

https://doi.org/10.5625/lar.2017.33.1.8

Wang Z, Wang H, Xu ZM, Ji YL, Chen YH, Zhang ZH, Zhang C, Meng XH, Zhao M, Xu DX. 2012. Cadmium-induced teratogenicity: association with ROS-mediated endoplasmic reticulum stress in placenta. Toxicology and Applied Pharmacology 259, 236-247.

https://doi.org/10.1016/j.taap.2012.01.001

Wu JY, Lin CY, Lin TW, Ken CF, Wen YD. 2007. Curcumin Affects Development of Zebrafish Embryo. Biological and Pharmaceutical Bulletin 30, 1336-1339.

https://doi.org/10.1248/bpb.30.1336

Julliane Monique A. Tagala, Alicia Magdalene Q. Biteng, Jocelyn R. Rafanan, Mayer L. Calma.
Maternal curcumin exposure causes fetal gross morphological anomalies and skeletal malformations in mouse.
Int. J. Biosci. 16(2), 382-393, February 2020.
https://innspub.net/ijb/maternal-curcumin-exposure-causes-fetal-gross-morphological-anomalies-skeletal-malformations-mouse/
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