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Involvement of proinflammatory cytokines and metallothionein in the repairing of arsenic-mediated uterine tissue damage by curcumin

  • Hasina Perveen , Sandip Chattopadhyay EMAIL logo , Moulima Maity , Moumita Dash and Syed Sirajul Islam
Published/Copyright: June 13, 2019

Abstract

Background

Curcumin is extensively used as a therapeutic intervention for treating several ailments. The antioxidant curcumin has an anti-inflammatory and chelating property with arsenic to exhibit a strong therapeutic effect on reproductive organs. This study was undertaken to describe the protective effect of noninvasive administration of curcumin against sodium-arsenite-mediated uterine hazards in female Wistar rats.

Methods

Twenty-four female Wistar rats were randomly divided into four groups. The treatment was continued for 8 days and given orally sodium arsenite (10 mg/kg body weight) in combination with curcumin (20 mg/kg body weight).

Results

Our evaluation revealed that 8 days of sodium arsenite (10 mg/kg body weight) treatment reduced the activities of the uterine enzymatic antioxidants superoxide dismutase, catalase, and peroxidase. Blood levels of vitamin B12 and folic acid decreased followed by an increased serum lactate dehydrogenase, homocysteine level, and hepatic metallothionein-1 in arsenic-treated rats. Necrosis of uterine tissue along with the disruption of ovarian steroidogenesis was marked in arsenic-treated rats with an upregulation of uterine NF-κB and IL-6 along with a raised level of serum TNF-α. Oral administration of curcumin (20 mg/kg body weight/day) in arsenic-treated rats significantly reinstated these alterations of the antioxidant system followed by an improvement of ovarian steroidogenesis and the circulating level of B12 and folate along with the downregulation of serum homocysteine, metallothionein-1, and cytokines.

Conclusions

The findings of this study clearly and strongly elucidated that arsenic-induced oxidative stress in uterus is linked to an alteration of inflammation-signaling biomarkers and these have been protected through the co-administration of curcumin due to its anti-inflammatory, free radical scavenging, and antioxidant activity by the possible regulation of an S-adenosine methionine pool.

Funding source: UGC

Award Identifier / Grant number: MANF-2014-15-MUS-WES-35512

Funding statement: This research work is partially supported by UGC Maulana Azad National Fellowship Scheme (Funder Id: 10.13039/501100001501, MANF-2014-15-MUS-WES-35512).

  1. Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

  2. Employment or leadership: None declared.

  3. Honorarium: None declared.

  4. Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.

References

[1] Chattopadhyay S, Ghosh D. The involvement of hypophyseal-gonadal and hypophyseal-adrenal axes in arsenic-mediated ovarian and uterine toxicity: modulation by hCG. J Biochem Mol Toxicol 2010;24:29–41.10.1002/jbt.20309Search in Google Scholar PubMed

[2] Tamura H, Takasaki A, Taketani T, Tanabe M, Kizuka F, Lee L, et al. Melatonin as a free radical scavenger in the ovarian follicle. Endocr J 2013;60:1–13.10.1507/endocrj.EJ12-0263Search in Google Scholar PubMed

[3] Chatterjee A, Chatterji U. Arsenic abrogates the estrogen-signaling pathway in the rat uterus. Reprod Biol Endocrinol 2010;8:80.10.1186/1477-7827-8-80Search in Google Scholar PubMed PubMed Central

[4] Flora SJ, Pachauri V. Chelation in metal intoxication. Int J Environ Res Public Health 2010;7:2745–88.10.3390/ijerph7072745Search in Google Scholar PubMed PubMed Central

[5] Gilman AG, Goodman LS, Rall T, Murad R, editors. Goodman and Gilman’s, the pharmacological basis of therapeutics, 7th ed. NY: Macmillan Publishing Co., 1985.Search in Google Scholar

[6] Kosnett MJ. The role of chelation in the treatment of arsenic and mercury poisoning. J Med Toxicol 2013;9:347–54.10.1007/s13181-013-0344-5Search in Google Scholar PubMed PubMed Central

[7] Chattopadhyay S, Misro M, Debnath J, Ghosh D. Supplementary effect of α tocopherol succinate (vitamin E) on sodium arsenite-induced ovarian steroidogenic function and plasma levels of gonadotrophins in mature albino rats. Tox Sub Mech 2000;19:137–50.10.1080/107691800300119356Search in Google Scholar

[8] Chattopadhyay S, Pal S, Ghosh D, Debnath J. Effect of dietary co-administration of sodium selenite on sodium arsenite-induced ovarian and uterine disorders in mature albino rats. Toxicol Sci 2003;75:412–22.10.1093/toxsci/kfg194Search in Google Scholar PubMed

[9] Maity M, Perveen H, Dash M, Jana S, Khatun S, Dey A, et al. Arjunolic acid improves the serum level of vitamin B12 and folate in the process of the attenuation of arsenic induced uterine oxidative stress. Biol Trace Elem Res 2018;182:78–90.10.1007/s12011-017-1077-0Search in Google Scholar PubMed

[10] Gupta SC, Patchva S, Koh W, Aggarwal BB. Discovery of curcumin, a component of golden spice, and its miraculous biological activities. Clin Exp Pharmacol Physiol 2012;39:283–99.10.1111/j.1440-1681.2011.05648.xSearch in Google Scholar PubMed PubMed Central

[11] Chattopadhyay I, Bandyopadhyay U, Biswas K, Maity P, Banerjee RK. Indomethacin inactivates gastric peroxidase to induce reactive-oxygen-mediated gastric mucosal injury and curcumin protects it by preventing peroxidase inactivation and scavenging reactive oxygen. Free Radic Biol Med 2006;40:1397–408.10.1016/j.freeradbiomed.2005.12.016Search in Google Scholar PubMed

[12] Perveen H, Dash M, Khatun S, Maity M, Islam SS, Chattopadhyay S. Electrozymographic evaluation of the attenuation of arsenic induced degradation of hepatic SOD, catalase in an in vitro assay system by pectic polysaccharides of Momordica charantia in combination with curcumin. Biochem Biophys Rep 2017;23:64–71.10.1016/j.bbrep.2017.06.002Search in Google Scholar

[13] Devasagayam TP, Boloor KK, Ramasarma T. Methods for estimating lipid peroxidation: an analysis of merits and demerits. Indian J Biochem Biophys 2003;40:300–8.Search in Google Scholar

[14] Kumar A. Effect of simvastatin on paraoxonase 1 (PON1) activity and oxidation stress. In: Kumar A, editor. Significance of lipid profile assay as diagnostic and prognostic tool. California: Create space independent publishing platform, 2012:105–9.Search in Google Scholar

[15] Pattichis K, Louca LL, Glover V. Quantitation of soluble superoxide dismutase in rat striata, based on the inhibition of nitrite formation from hydroxylammonium chloride. Anal Biochem 1994;221:428–31.10.1006/abio.1994.1441Search in Google Scholar

[16] Hadwan MH. New method for assessment of serum catalase activity. Indian J Sci Technol 2016;9:1–5.10.17485/ijst/2016/v9i4/80499Search in Google Scholar

[17] Sadasivan S, Manickam A. Peroxidase. In: Sadasivan S, Manickam, editors. Methods in biochemistry. New Delhi: New Age International Publishers, 1966:108–10.Search in Google Scholar

[18] Weydert CJ, Cullen JJ. Measurement of superoxide dismutase, catalase and glutathione peroxidase in cultured cells and tissue. Nat Protoc 2010;5:51–66.10.1038/nprot.2009.197Search in Google Scholar

[19] Lewis A, Du J, Liu J, Ritchie JM, Oberley LW, Cullen JJ. Metastatic progression of pancreatic cancer: changes in antioxidant enzymes and cell growth. Clin Exp Metastasis 2005;22:523–32.10.1007/s10585-005-4919-7Search in Google Scholar

[20] Hasan HR, Aburahma NN. Electrophoresis profile of total peroxidases in sera and saliva of patients with different oral tumors. Oriental J Chem 2014;30:81–6.10.13005/ojc/300110Search in Google Scholar

[21] Brandt RB, Laux JE, Spainhour SE, Kline ES. Lactate dehydrogenase in rat mitochondria. Arch Biochem Biophys 1987;259:412–22.10.1016/0003-9861(87)90507-8Search in Google Scholar

[22] Singh NP, McCoy MT, Tice RR, Schneider EL. A simple technique for quantitation of low levels of DNA damage in individual cells. Exp Cell Res 1988;175:184–91.10.1016/0014-4827(88)90265-0Search in Google Scholar

[23] Garcia-Martinez V, Macias D, Gañan Y, Garcia-Lobo JM, Francia MV, Fernandez-Teran MA, et al. Inter nucleosomal DNA fragmentation and programmed cell death (apoptosis) in the interdigital tissue of the embryonic chick leg bud. J Cell Sci 1993;106:201–8.10.1242/jcs.106.1.201Search in Google Scholar

[24] Talalay P, editor. Hydroxysteroid dehydrogenase. In: Colowick SP, Kaplan NO, editors. Methods in enzymology. New York: Academic Press, 1962:512–6.10.1016/S0076-6879(62)05269-6Search in Google Scholar

[25] Jarabak J, Adams JA, Williams-Ashman HG, Talay P. Purification of a 17beta-hydroxysteroid dehydrogenase of human placenta and studies on its transhydrogenase function. J Biol Chem 1962;237:345–57.10.1016/S0021-9258(18)93926-8Search in Google Scholar

[26] Manna P, Sinha M, SilP C. Protection of arsenic-induced hepatic disorder by arjunolic acid. Basic Clin Pharmacol Toxicol 2007;101:333–8.10.1111/j.1742-7843.2007.00132.xSearch in Google Scholar PubMed

[27] Giberson A, Vaziri ND, Mirahamadi K, Rosen SM. Hemodialysis of acute arsenic intoxication with transient renal failure. Arch Intern Med 1976;136:1303–4.10.1001/archinte.1976.03630110065017Search in Google Scholar

[28] Wang XN, Zhang CJ, Diao HL, Zhang Y. Protective effects of curcumin against sodium arsenite-induced ovarian oxidative injury in a mouse model. Chinese Med J (Engl) 2017;130:1026–32.10.4103/0366-6999.204927Search in Google Scholar PubMed PubMed Central

[29] Ray G, Husain SA. Oxidants, antioxidants and carcinogenesis. Indian J Exp Biol 2002;40:1213–32.Search in Google Scholar

[30] Hoffbrand AV, Kremenchuzky S, Butterworth PJ, Mollin DL. Serum lactic dehydrogenase activity and folate deficiency in myelosclerosis and other haematological diseases. Br Med J 1966;1:577–81.10.1136/bmj.1.5487.577Search in Google Scholar PubMed PubMed Central

[31] Rydberg B, Lindahl T. Nonenzymatic methylation of DNA by the intracellular methyl group donor S-adenosyl-L-methionine is a potentially mutagenic reaction. EMBO J 1982;1:211–6.10.1002/j.1460-2075.1982.tb01149.xSearch in Google Scholar PubMed PubMed Central

[32] Faraci FM, Didion SP. Vascular protection: superoxide dismutase isoforms in the vessel wall. Arterioscler Thromb Vasc Biol 2004;24:1367–73.10.1161/01.ATV.0000133604.20182.cfSearch in Google Scholar PubMed

[33] Gamble MV, Liu X, Ahsan H, Pilsner JR, Ilievski V, Slavkovich V, et al. Folate and arsenic metabolism: a double-blind, placebo-controlled folic acid-supplementation trial in Bangladesh. Am J Clin Nutr 2006;84:1093–101.10.1093/ajcn/84.5.1093Search in Google Scholar PubMed PubMed Central

[34] Ma J, Stampfer MJ, Christensen B, Giovannucci E, Hunter DJ, Chen J, et al. A polymorphism of the methionine synthase gene: association with plasma folate, vitamin B12, homocysteine, and colorectal cancer risk. Cancer Epidemiol Biomarkers Prev 1999;8:825–9.Search in Google Scholar

[35] Refsum H. Folate, vitamin B12 and homocysteine in relation to birth defects and pregnancy outcome. Br J Nutr 2001;85:9–13.10.1079/BJN2000302Search in Google Scholar

[36] Kanakkaparambil R, Singh R, Li D, Webb R, Sinclair KD. B-vitamin and homocysteine status determines ovarian response to gonadotropin treatment in sheep. Biol Reprod 2009;80:743–52.10.1095/biolreprod.108.072074Search in Google Scholar PubMed PubMed Central

[37] Vanselow J, Pöhland R, Fürbass R. Promoter-2-derived Cyp19 expression in bovine granulosa cells coincides with gene-specific DNA hypo-methylation. Mol Cell Endocrinol 2005;233:N57–64.10.1016/j.mce.2005.01.007Search in Google Scholar PubMed

[38] Weiss N. Mechanisms of increased vascular oxidant stress in hyperhomocys-teinemia and its impact on endothelial function. Curr Drug Metab 2005;6:27–36.10.2174/1389200052997357Search in Google Scholar PubMed

[39] Poddar R, Sivasubramanian N, DiBello PM, Robinson K, Jacobsen DW. Homocysteine induces expression and secretion of monocyte chemoattractant protein-1 and interleukin-8 in human aortic endothelial cells: implications for vascular disease. Circulation 2001;103:2717–23.10.1161/01.CIR.103.22.2717Search in Google Scholar

[40] Karin M, Ben-Neriah Y. Phosphorylation meets ubiquitination: the control of NF-[kappa]B activity. Annu Rev Immunol 2000;18:621–63.10.1146/annurev.immunol.18.1.621Search in Google Scholar PubMed

[41] Nishi T, Shimizu N, Hiramoto M, Sato I, Yamaguchi Y, Hasegawa M, et al. Spatial redox regulation of a critical cysteine residue of NF-κB in vivo. J Biol Chem 2002;277:44548–56.10.1074/jbc.M202970200Search in Google Scholar PubMed

[42] Da Cunha AA, Horn AP, Hoppe JB, Grudzinski PB, Loureiro SO, Ferreira AG, et al. Evidence that AKT and GSK-3β pathway are involved in acute hyperhomocysteinemia. Int J Dev Neurosci 2012;30:369–74.10.1016/j.ijdevneu.2012.04.001Search in Google Scholar PubMed

[43] Verderame M, Limatola E, Scudiero R. Metallothionein expression and synthesis in the testis of the lizard Podarcis sicula under natural conditions and following estrogenic exposure. Eur J Histochem 2017;61:2777.10.4081/ejh.2017.2777Search in Google Scholar PubMed PubMed Central

[44] Bhattacharya A, Bhattacharya S. Induction of oxidative stress by arsenic in Clarias batrachus: involvement of peroxisomes. Ecotoxicol Environ Saf 2007;66:178–87.10.1016/j.ecoenv.2005.11.002Search in Google Scholar PubMed

[45] Peng Z, Peng L, Fan Y, Zandi E, Shertzer HG, Xia Y. A critical role for IkappaB kinase beta in metallothionein-1 expression and protection against arsenic toxicity. J Biol Chem 2007;282:21487–96.10.1074/jbc.M702510200Search in Google Scholar PubMed

[46] El-Demerdash FM, Yousef MI, Radwan FM. Ameliorating effect of curcumin on sodium arsenite-induced oxidative damage and lipid peroxidation in different rat organs. Food Chem Toxicol 2009;47:249–54.10.1016/j.fct.2008.11.013Search in Google Scholar PubMed

[47] Yousef MI, El-Demerdash FM, Radwan FM. Sodium arsenite induced biochemical perturbations in rats: ameliorating effect of curcumin. Food Chem Toxicol. 2008;46:3506–11.10.1016/j.fct.2008.08.031Search in Google Scholar PubMed

[48] Aktas C, Kanter M, Kocak Z. Antiapoptotic and proliferative activity of curcumin on ovarian follicles in mice exposed to whole body ionizing radiation. Toxicol Ind Health 2012;28:852–63.10.1177/0748233711425080Search in Google Scholar

[49] Esatbeyoglu T, Huebbe P, Ernst IM, Chin D, Wagner AE, Rimbach G. Curcumin – from molecule to biological function. Angew Chem Int Ed Engl 2012;51:5308–32.10.1002/anie.201107724Search in Google Scholar

[50] Phan TT, See P, Lee ST, Chan SY. Protective effects of curcumin against oxidative damage on skin cells in vitro: its implication for wound healing. J Trauma Acute Care Surg 2001;51:927–31.10.1097/00005373-200111000-00017Search in Google Scholar

[51] Reddy AC, Lokesh BR. Effect of dietary turmeric (Curcuma longa) on iron-induced lipid peroxidation in the rat liver. Food Chem Toxicol 1994;32:279–83.10.1016/0278-6915(94)90201-1Search in Google Scholar

[52] Marcus J, Sarnak MJ, Menon V. Homocysteine lowering and cardiovascular disease risk: lost in translation. Can J Cardiol 2007;23:707–10.10.1016/S0828-282X(07)70814-0Search in Google Scholar

[53] Devi YS, De Vine M, De Kuiper J, Ferguson S, Fazleabas AT. Inhibition of IL-6 signaling pathway by curcumin in uterine decidual cells. PLoS One 2015;10:e0125627.10.1371/journal.pone.0125627Search in Google Scholar PubMed PubMed Central

[54] Singh S, Aggarwal BB. Activation of transcription factor NF-kappa B is suppressed by curcumin (diferuloylmethane). J Biol Chem 1995;270:24995–5000.10.1074/jbc.270.42.24995Search in Google Scholar PubMed

[55] Das L, Vinayak M. Long-term effect of curcumin down-regulates expression of tumor necrosis factor-α and interleukin-6 via modulation of E26 transformation-specific protein and nuclear factor-κB transcription factors in livers of lymphoma bearing mice. Leuk Lymphoma 2014;55:2627–36.10.3109/10428194.2014.889824Search in Google Scholar PubMed

[56] Li J, Luo M, Xie N, Wang J, Chen L. Curcumin protects endothelial cells against homocysteine induced injury through inhibiting inflammation. Am J Transl Res 2016;8:4598–604.Search in Google Scholar

[57] Cianciulli A, Salvatore R, Porro C, Trotta T, Panaro MA. Folic acid is able to polarize the inflammatory response in LPS activated microglia by regulating multiple signaling pathways. Mediators Inflamm 2016;2016:5240127.10.1155/2016/5240127Search in Google Scholar PubMed PubMed Central

[58] Al-Daghri NM, Rahman S, Sabico S, Yakout S, Wani K, Al-Attas OS, et al. Association of vitamin B12 with pro-inflammatory cytokines and biochemical markers related to cardiometabolic risk in Saudi subjects. Nutrients 2016;8:460.10.3390/nu8090460Search in Google Scholar PubMed PubMed Central

[59] Yadav A, Lomash V, Samim M, Flora SJ. Curcumin encapsulated in chitosan nanoparticles: a novel strategy for the treatment of arsenic toxicity. Chem Biol Interact 2012;199:49–61.10.1016/j.cbi.2012.05.011Search in Google Scholar PubMed

[60] Gao S, Duan X, Wang X, Dong D, Liu D, Li X, et al. Curcumin attenuates arsenic-induced hepatic injuries and oxidative stress in experimental mice through activation of Nrf2 pathway, promotion of arsenic methylation and urinary excretion. Food Chem Toxicol 2013;59:739–47.10.1016/j.fct.2013.07.032Search in Google Scholar PubMed

[61] Lao CD, Ruffin MT, Normolle D. Dose escalation of a curcuminoid formulation. BMC Complement Altern Med 2006;6:10.10.1186/1472-6882-6-10Search in Google Scholar PubMed PubMed Central

[62] Shoba G, Joy D, Joseph T, Majeed M, Rajendran R, Srinivas PS. Influence of piperine on the pharmacokinetics of curcumin in animals and human volunteers. Planta Med 1998;64:353–6.10.1055/s-2006-957450Search in Google Scholar PubMed

[63] Chang MT, Tsai TR, Lee CY, Wei YS, Chen YJ, Chen CR, et al. Elevating bioavailability of curcumin via encapsulation with a novel formulation of artificial oil bodies. J Agric Food Chem 2013;61:9666–71.10.1021/jf4019195Search in Google Scholar PubMed

Received: 2017-10-22
Accepted: 2019-01-18
Published Online: 2019-06-13

© 2019 Walter de Gruyter GmbH, Berlin/Boston

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