Brown Rice Extract Ameliorates Oxidative Status in Human Placental Cell Line (JEG-3) Induced by Cadmium Chloride


  • Tantip BOONSONG Department of Biochemistry, Faculty of Medical Science, Naresuan University, Phitsanulok 65000, Thailand
  • Wajathip BULANAWICHIT Department of Biochemistry, Faculty of Medical Science, Naresuan University, Phitsanulok 65000, Thailand


Cadmium, JEG-3, Brown rice, Oxidative status, Antioxidant


Cadmium (Cd) can induce oxidative stress by producing reactive oxygen species (ROS) and affect the antioxidant defense systems, leading to cellular damage. Supplementation with antioxidants may protect against Cd-induced oxidative stress. This study aimed to investigate the effect of germinated brown rice (GBR), brown rice (BR), and white rice (WR) extracts against Cd-induced toxicity in human placenta (JEG-3) cells. The cytotoxicity of Cd and rice extracts was measured by MTT assay, and pre-treatments with GBR, BR, and WR before Cd exposure were examined. Intracellular ROS levels and the expression of SOD2 and GPx4 were determined by DCFH-DA assay and western blot, respectively. An antioxidant N-acetylcysteine (NAC) was used as a positive control. The antioxidant capacity and total phenolic content of rice extracts were investigated by DPPH and Folin-Ciocalteu methods, respectively. The GBR extract exhibited the highest antioxidant activity and total phenolic content, followed by BR and WR, respectively. Cd decreased cell viability in a dose-dependent manner, whereas incubation with 0.1 - 0.5 mg/mL showed no toxicity in all rice extracts. Moreover, Cd treatments significantly (p < 0.05) increased ROS levels. Conversely, treatments with GBR and BR extracts decreased ROS. Similar results were observed for combinatorial treatments of GBR and BR with Cd, except for WR treatment. Additionally, significant increased SOD2 and decreased GPx4 expression levels were evident in the GBR group and in both GBR and BR pre-treated groups, respectively, compared to Cd exposure alone. These results suggest that brown rice pre-treatments may ameliorate oxidative status induced by Cd in cultured human placental cells.


Download data is not yet available.


Metrics Loading ...


L Järup and A Akesson. Current status of cadmium as an environmental health problem. Toxicol. Appl. Pharmacol. 2009; 238, 201-8.

RK Zalups and S Ahmad. Molecular handling of cadmium in transporting epithelia. Toxicol. Appl. Pharmacol. 2003; 186, 163-88.

J Godt, F Scheidig, C Grosse-Siestrup, V Esche, P Brandenburg, A Reich and DA Groneberg. The toxicity of cadmium and resulting hazards to human health. J.Occup. Med. Toxic. 2006; 1, 22.

A Sarkar, G Ravindran and VA Krishnamurthy. Brief review on the effect of cadmium toxicity: From cellular to organ level. Int. J. Biotechnol. Res. 2013; 3, 17-36.

RM Rafati, RM Rafati, S Kazemi and AA Moghadamnia. Cadmium toxicity and treatment: An update. Caspian J. Intern. Med. 2017; 8, 135-45.

A El-Sayed, MS Salem, AE Amany, AR Zeinab and MK Asmaa. Protective effect of zinc against cadmium toxicity on pregnant rats and their fetuses at morphological, physiological and molecular level. Afr. J. Biotechnol. 2013; 12, 2110-9.

GB Zhang, H Wang, J Hu, MY Guo, Y Wang, Y Zhou, Z Yu, L Fu, YH Chen and DX Xu. Cadmium-induced neural tube defects and fetal growth restriction: Association with disturbance of placental folate transport. Toxicol. Appl. Pharmacol.2016; 306, 79-85.

C Dechanet, T Anahory, JC Mathieu Daude, X Quantin, L Reyftmann, S Hamamah, B Hedon and H Dechaud. Effects of cigarette smoking on reproduction. Hum. Reprod. Update. 2011; 17, 76-95.

Saad AA, Hegazy NM, Amer N, Gaber K, Youssef AI, Sharaf NE and NAM Diab. The role of cadmium exposure on spontaneous abortion. World J. Med. Sci. 2012; 7, 270-5.

Cuypers A, Plusquin M, Remans T, Jozefczak M, Keunen E, Gielen H, K Opdenakker, AR Nair, E Munters, TJ Artois, T Nawrot, J Vangronsveld and K Smeets. Cadmium stress: An oxidative challenge. Biometals 2010; 23, 927-40.

JB Samuel, J Stanley, RA Princess, P Shanthi and MS Sebastian. Gestational cadmium exposure-induced ovotoxicity delays puberty through oxidative stress and impaired steroid hormone levels. J. Med. Toxicol. 2011; 7, 195-204.

K Jomova and M Valko. Advances in metal-induced oxidative stress and human disease. Toxicology 2011; 283, 65-87.

SJ Flora. Structural, chemical and biological aspects of antioxidants for strategies against metal and metalloid exposure. Oxid. Med. Cell. Longev. 2009; 2, 191-206.

M Kanter, B Aksu, M Akpolat, YT Tarladacalisir, C Aktas and H Uysal. Vitamin E protects against oxidative damage caused by cadmium in the blood of rats. Eur. J. Gen. Med. 2009; 6, 154-60.

HM Abdou, NA Mohamed, DAE Mekkawy and SB EL-Hengary. Vitamin E and/or wheat germ oil supplementation ameliorate oxidative stress induced by cadmium chloride in pregnant rats and their fetuses. Jordan J. Biol. Sci. 2017; 10, 39-48.

RR Devi and C Arumughan. Phytochemical characterization of defatted rice bran and optimization of a process for their extraction and enrichment. Biores. Technol. 2007; 98, 3037-43.

MJ Lerma-Garcia, JM Herrero-Martinez, EF Simo-Alfonso, CRB Mendonca and G Ramis-Ramos. Composition, industrial processing and applications of rice bran gamma-oryzanol. Food Chem. 2009; 115, 389-404.

SB Patil and K Khan. Germinated brown rice as a value added rice product: A review. J. Food Sci. Technol. 2011; 48, 661-7.

MJ Son, CW Rico, SH Nam and MY Kang. Influence of oryzanol and ferulic acid on the lipid metabolism and antioxidative status in high fat-fed mice. J. Clin. Biochem. Nutr. 2010; 46, 150-6.

MS Islam, T Murata, M Fujisawa, R Nagasaka, H Ushio, AM Bari, M Hori and H Ozaki. Anti-inflammatory effects of phytosteryl ferulates in colitis induced by dextran sulphate sodium in mice. Br. J. Pharmacol. 2008; 154, 812-24.

BL Tan and ME Norhaizan.Scientific evidence of rice by-products for cancer prevention: chemopreventive properties of waste products from rice milling on carcinogenesis in vitro and in vivo. BioMed Res. Int. 2017; 2017, 1-18.

MJ Son, CW Rico, SH Nam and MY Kang. Effect of oryzanol and ferulic acid on the glucose metabolism of mice fed with a high-fat diet. J. Food Sci. 2011; 76, H7-H10.

IO Minatel, FV Francisqueti, CR Corrêa, and GPP Lima. Antioxidant activity of γ-oryzanol: A complex network of interactions. Int. J. Mol. Sci. 2016; 17, 1107.

SB Patil and K Khan. Germinated brown rice as a value added rice product: A review. J. Food Sci. Technol. 2011; 48, 661-7.

JN Ho, ME Son, WC Lim, ST Lim and HY Cho. Germinated brown rice extract inhibits adipogenesis through the down-regulation of adipogenic genes in 3T3-L1 adipocytes. Plant Foods Hum. Nutr. 2013; 68, 274-8.

FJ Lin, JW Fitzpatrick, CA lannotti, DS Martin, BD Mariani and RS Tuan. Effects of Cadmium on Trophoblast Calcium Transport. Placenta 1997; 18, 341-56.

SJ Stohs, D Bagchi, E Hassoun and M Bagchi. Oxidative mechanisms in the toxicity of chromium and cadmium ions. J. Environ. Pathol. Toxicol. Oncol. 2001; 202, 77-88.

N Ercal, H Gurer-Orhan and N Aykin-Burns. Toxic metals and oxidative stress part I: Mechanisms involved in metal-induced oxidative damage. Curr. Top. Med. Chem. 2001; 1, 529-39.

U Kukongviriyapan, K Apaijit and V Kukongviriyapan. Oxidative stress and cardiovascular dysfunction associated with cadmium exposure: Beneficial effects of curcumin and tetrahydrocurcumin. Tohoku J. Exp. Med. 2016; 239, 25-38.

I Al-Saleh, N Shinwari, A Mashhour, GElD Mohamed and A Rabah. Heavy metals (lead, cadmium and mercury) in maternal, cord blood and placenta of healthy women. Int. J. Hyg. Environ. Health. 2011; 214, 79-101.

M Kippler, AM Hoque, R Raqib, H Öhrvik, EC Ekström and M Vahter. Accumulation of cadmium in human placenta interacts with the transport of micronutrients to the fetus. Toxicol. Lett. 2010; 192, 162-8.

AM Ronco, G Arguello, L Munoz, N Gras and M Llanos. Metals content in placentas from moderate cigarette consumers: Correlation with newborn birth weight. Biometals 2005; 18, 233-41.

S Stasenko, EM Bradford, M Piasek, MC Henson, VM Varnai, J Jurasovic and V Kusec. Metals in human placenta: focus on the effects of cadmium on steroid hormones and leptin. J. Appl. Toxicol. 2010; 30, 242-53.

M Erboga and M Kanter. Effect of cadmium on trophoblast cell proliferation and apoptosis in different gestation periods of rat placenta. Biol. Trace Elem. Res. 2016; 169, 285-93.

AM Ronco, E Llaguno, MJ Epuñan and MN Llanos. Effect of cadmium on cortisol production and 11b-hydroxysteroid dehydrogenase 2 expression by cultured human choriocarcinoma cells (JEG-3). Toxicol. In Vitro. 2010; 24, 1532-7.

J Banchuen, P Thammarutwasik, B Ooraikul, P Wuttijumnong and P Sirivongpaisal. Effect of germinating processes on bioactive component of sangyodmuangphatthalung rice. Thai J. Agric. Sci. 2009; 42, 191-9.

S Tian, K Nakamura and H Kayahara. Analysis of phenolic compounds in white rice, brown rice, and germinated brown rice. J. Agric. Food Chem. 2004; 52, 4808-13.

A Ghasemzadeh, HZ Jaafar, AS Juraimi and A Tayebi-Meigooni. Comparative evaluation of diferent extraction techniques and solvents for the assay of phytochemicals and antioxidant activity of Hashemi rice bran. Molecules 2015; 20, 10822-38.

IM Sani, S Iqbal, KW Chan and M Ismail. Effect of acid and base catalyzed hydrolysis on the yield of phenolics and antioxidant activity of extracts from germinated brown rice (GBR). Molecules 2012; 17, 7584-94.

W Bulanawichit, T Kirdin and T Boonsong. Effects of brown rice and germinated brown rice extracts from Thai rice cultivars (PL2 and KDML105) on adipogenic, adipocytokine, and antioxidant genes in 3T3-L1 adipocytes. Chiang Mai Univ. J. Nat. Sci. 2018; 17, 79-96.

M Patel and SN Naik. Gamma-oryzanol from rice bran oil: A review. J. Sci. Ind. Res. 2004; 63, 569-78.

H Kikuzaki, M Hisamoto, K Hirose, K Akiyama and H Taniguchi. Antioxidant properties of ferulic acid and its related compounds. J. Agric. Food Chem. 2002; 50, 2161-9.

S Itagaki, T Kurokawa, C Nakata, Y Saito, S Oikawa, M Kobayashi, T Hirano and K Iseki. In vitro and in vivo antioxidant properties of ferulic acid: A comparative study with other natural oxidation inhibitors. Food Chem. 2009; 114, 466-71.

JC Hu, XT Zou and DR Cao. Effect of gamma-aminobutyric acid on serum biochemical parameter of finishing hogs in summer. LiaoNing (P.R.China). Feed Ind. 2008; 29, 9-11.

OM Ighodaro and OA Akinloye. First line defence antioxidants-superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX): Their fundamental role in the entire antioxidant defence grid. Alexandria J. Med. 2018; 54, 287-93.

L Järup, M Berglund, CG Elinder, G Nordberg abd M Vahter. Health effects of cadmium exposure- a review of the literature and a risk estimate. Scand. J. Work Environ. Health 1998; 24, 1-5.

YL Zhang, YC Zhao, JX Wang, HD Zhu, QF Liu, YG Fan, NF Wang, JH Zhao, HS Liu, L Ou-Yang, AP Liu and TQ Fan. Effect of environmental exposure to cadmium on pregnancy outcome and fetal growth: a study on healthy pregnant women in China. J. Environ. Sci. Health A Tox. Hazard Subst. Environ. Eng. 2004; 39, 2507-15.




How to Cite

BOONSONG, T. ., & BULANAWICHIT, W. . (2020). Brown Rice Extract Ameliorates Oxidative Status in Human Placental Cell Line (JEG-3) Induced by Cadmium Chloride. Walailak Journal of Science and Technology (WJST), 17(8), 880-892. Retrieved from