Methylmercury Intoxication Promotes Metallothionein Response and Cell Damage in Salivary Glands of Rats
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Environmental and occupational mercury exposure is considered a major public health issue. Despite being well known that MeHg exposure causes adverse effects in several physiologic functions, MeHg effects on salivary glands still not completely elucidated. Here, we investigated the cellular MeHg-induced damage in the three major salivary glands (parotid, submandibular, and sublingual) of adult rats after chronic, systemic and low doses of MeHg exposure. Rats were exposed by 0.04 mg/kg/day over 60 days. After that, animals were euthanized and all three glands were collected. We evaluated total Hg accumulation, metallothionein I/II (MT I/II), α-smooth muscle actin (α-SMA), and cytokeratin 18 (CK18) immune expression. Our results have showed that MeHg is able to disrupt gland tissue and to induce a protective mechanism by MT I/II expression. We also showed that cell MT production is not enough to protect gland tissue against cellular structural damage seen by reducing marking of cytoskeletal proteins as CK18 and α-SMA. Our data suggest that chronic MeHg exposure in low-daily doses is able to induce cellular damage in rat salivary glands.
KeywordsMeHg Mercury Salivary gland Metallothionein Intoxication
This work was supported by the Brazilian National Council for Scientific and Technological Development (CNPq), Fundação de Amparo a Pesquisa do Estado do Pará (FAPESPA), and Pró-Reitoria de Pesquisa e Pós-Graduação da UFPA (PROPESP, UFPA, Brazil). Leidiane A. O. Lima is a scholar supported by UFPA. Rafael R. Lima is an investigator from CNPq (Edital MCTI/CNPQ/Universal 14/2014).
Compliance with Ethical Standards
All procedures were previously approved by Ethics committee on animal experimentation by Federal University of Para (BIO 225-14 - CEPAE-UFPA) following the guidelines suggested by NIH Guide to Care and Use of Laboratory Animals.
- 8.Bittencourt LO, Puty B, Charone S, WAB A, Farias-Junior PM, MCF S, Crespo-Lopez ME, AdL L, MAR B, Lima RR (2017) Oxidative Biochemistry Disbalance and Changes on Proteomic Profile in Salivary Glands of Rats Induced by Chronic Exposure to Methylmercury. Oxidative Med Cell Longev 2017:15. https://doi.org/10.1155/2017/5653291 CrossRefGoogle Scholar
- 9.Islas-Granillo H, Borges-Yanez A, Fernandez-Barrera MA, Avila-Burgos L, Patino-Marin N, Marquez-Corona ML, Mendoza-Rodriguez M, Medina-Solis CE (2017) Relationship of hyposalivation and xerostomia in Mexican elderly with socioeconomic, sociodemographic and dental factors. Sci Rep 7:40686. https://doi.org/10.1038/srep40686 CrossRefPubMedPubMedCentralGoogle Scholar
- 13.Teixeira FB, Fernandes RM, Farias-Junior PM, Costa NM, Fernandes LM, Santana LN, Silva-Junior AF, Silva MC, Maia CS, Lima RR (2014) Evaluation of the effects of chronic intoxication with inorganic mercury on memory and motor control in rats. Int J Environ Res Public Health 11(9):9171–9185. https://doi.org/10.3390/ijerph110909171 CrossRefPubMedPubMedCentralGoogle Scholar
- 17.da Costa NM, Correa RS, Junior IS, Figueiredo AJ, Vilhena KF, Farias-Junior PM, Teixeira FB, Ferreira NM, Pereira-Junior JB, Dantas K, da Silva MC, Silva-Junior AF, Alves-Junior Sde M, Pinheiro Jde J, Lima RR (2014) Physical, chemical, and immunohistochemical investigation of the damage to salivary glands in a model of intoxication with aluminium citrate. Int J Environ Res Public Health 11(12):12429–12440. https://doi.org/10.3390/ijerph111212429 CrossRefPubMedPubMedCentralGoogle Scholar
- 18.Silva AF, Aguiar MS, Carvalho OS, Santana Lde N, Franco EC, Lima RR, Siqueira NV, Feio RA, Faro LR, Gomes-Leal W (2013) Hippocampal neuronal loss, decreased GFAP immunoreactivity and cognitive impairment following experimental intoxication of rats with aluminum citrate. Brain Res 1491:23–33. https://doi.org/10.1016/j.brainres.2012.10.063 CrossRefPubMedGoogle Scholar
- 25.Fedirko NV, Kruglikov IA, Kopach OV, Vats JA, Kostyuk PG, Voitenko NV (2006) Changes in functioning of rat submandibular salivary gland under streptozotocin-induced diabetes are associated with alterations of Ca2+ signaling and Ca2+ transporting pumps. Biochim Biophys Acta 1762(3):294–303. https://doi.org/10.1016/j.bbadis.2005.12.002 CrossRefPubMedGoogle Scholar
- 28.Chan J, Huang Z, Merrifield ME, Salgado MT, Stillman MJ (2002) Studies of metal binding reactions in metallothioneins by spectroscopic, molecular biology, and molecular modeling techniques. Coord Chem Rev 233(Supplement C):319–339. https://doi.org/10.1016/S0010-8545(02)00176-5 CrossRefGoogle Scholar
- 30.Higashimoto M, Isoyama N, Ishibashi S, Inoue M, Takiguchi M, Suzuki S, Ohnishi Y, Sato M (2009) Tissue-dependent preventive effect of metallothionein against DNA damage in dyslipidemic mice under repeated stresses of fasting or restraint. Life Sci 84(17-18):569–575. https://doi.org/10.1016/j.lfs.2009.01.022 CrossRefPubMedGoogle Scholar
- 35.Nersesyan A, Kundi M, Waldherr M, Setayesh T, Misik M, Wultsch G, Filipic M, Mazzaron Barcelos GR, Knasmueller S (2016) Results of micronucleus assays with individuals who are occupationally and environmentally exposed to mercury, lead and cadmium. Mutat Res 770(Pt A):119–139. https://doi.org/10.1016/j.mrrev.2016.04.002 CrossRefPubMedGoogle Scholar
- 36.Crespo-Lopez ME, Macedo GL, Pereira SI, Arrifano GP, Picanco-Diniz DL, do Nascimento JL, Herculano AM (2009) Mercury and human genotoxicity: critical considerations and possible molecular mechanisms. Pharmacol Res 60(4):212–220. https://doi.org/10.1016/j.phrs.2009.02.011 CrossRefPubMedGoogle Scholar