Analysis of MT1 and ZIP1 gene expression in the liver of rats with chronic poisoning with cadmium chloride
https://doi.org/10.47470/0016-9900-2021-100-11-1298-1302
Abstract
Introduction. Cadmium is a toxic heavy metal with devastating effects on most organ systems. After absorption, cadmium is transported throughout the body, primarily by binding to proteins by metallothioneins. It is believed that the mechanisms of cadmium-induced transformation arise due to the disruption of zinc-dependent cellular processes. This part is due to the structural and physical similarities between zinc and cadmium. More than half of the incoming cadmium is deposited in the liver and kidneys. The rest part is distributed throughout other organs and their systems.
Materials and methods. In total, 40 white outbred rats of both sexes weighing 170–230 g were used in the experiment; they were formed into four experimental groups of 10 animals each, depending on the dose of the injected toxicant. Liver tissue samples were used as research materials, in the homogenate of which the quantitative content of Cd and Zn was determined, as well as the mRNA level of the MT1 and ZIP1 genes.
Results. It was found that the most pronounced activity of the MT1 gene in liver tissues was achieved when animals were administered cadmium chloride at a dose of 0.1 mg/kg (2.69 ± 0.37; p = 0.017), while the multiplicity of expression of the ZIP1 gene showed the maximum value of the level of transcripts with the minimum dose of toxin (2.70 ± 0.37; p = 0.007). It was also revealed that the highest concentration of zinc in the liver tissue was observed with the introduction of cadmium chloride at a dose of 0.1 mg/kg (33.84 ± 0.53; p <0.001), and the concentration of cadmium increased along with an increase in the dose of the toxicant (0, 0049 ± 0.0003; 0.0203 ± 0.0024; 0.664 ± 0.007; 0.76 ± 0.0089).
Conclusion. Thus, a comprehensive study of the expression of genes for metallothioneins and zinc transporters can be used as a biomarker of poisoning with cadmium and its compounds.
Contribution:
Ziatdinova M.M. — the concept and design of the study, the collection and processing of material, statistical processing, writing text;
Valova Ya.V. — collection and processing of the material;
Mukhammadiyeva G.F., Fazlieva A.S., Karimov D.D., Kudoyarov E.R. — collection and processing of the material.
All authors are responsible for the integrity of all parts of the manuscript and approval of the manuscript final version
Conflict of interest. The authors declare no conflict of interest.
Acknowledgement. The budget topic within the sectoral program of the Federal Service for Supervision in Protection of the Rights of Consumer and Man Wellbeing
Conclusion of the bioethical commission: the study was approved by the bioethical commission of the “Ufa Research Institute of Occupational Health and Human Ecology”, carried out per the European Convention for the Protection of Vertebrate Animals Used for Experiments or Other Scientific Purposes (ETS N 123), the directive of the European Parliament and the Council of the European Union 2010/63 / EU of 22.09.2010 on the protection of animals used for scientific purposes.
Received: May 20, 2021 / Accepted: September 28, 2021 / Published: November 30, 2021
About the Authors
Munira M. ZiatdinovaRussian Federation
Junior Researcher of the Department of Toxicology and Genetics with an experimental laboratory of laboratory animals, Ufa
Research Institute of Occupational Health and Human Ecology, Ufa, 450106, Russian Federation.
e-mail: munira.munirovna@yandex.ru
Yana V. Valova
Russian Federation
Guzel F. Mukhammadiyeva
Russian Federation
Anna S. Fazlieva
Russian Federation
Denis D. Karimov
Russian Federation
Eldar R. Kudoyarov
Russian Federation
References
1. Hu X., Chandler J.D., Park S., Liu K., Fernandes J., Orr M., et al. Low-dose cadmium disrupts mitochondrial citric acid cycle and lipid metabolism in mouse lung. Free Radic. Biol. Med. 2019; 131: 209-17. https://doi.org/10.1016/j.freeradbiomed.2018.12.005
2. Garrett S.H., Clarke K., Sens D.A., Deng Y., Somji S., Zhang K.K. Short- and long-term gene expression variation and networking in human proximal tubule cells when exposed to cadmium. BMC Med. Genomics. 2013; 6(Suppl. 1): S2. https://doi.org/10.1186/1755-8794-6-s1-s2
3. Genchi G., Sinicropi M.S., Lauria G., Carocci A., Catalano A. The Effects of Cadmium Toxicity. Int. J. Environ. Res. Public. Health. 2020; 17(11): 3782. https://doi.org/10.3390/ijerph17113782
4. Marettová E., Maretta M., Legáth J. Toxic effects of cadmium on testis of birds and mammals: a review. Anim. Reprod. Sci. 2015; 155: 1-10. https://doi.org/10.1016/j.anireprosci.2015.01.007
5. Massányi P., Uhrín V., Toman R., Pivko J., Lukáč N., Forgács Z., et al. Ultrastructural changes of ovaries in rabbits following cadmium administration. Acta Vet. Brno. 2005; 74(1): 29-35. https://doi.org/10.2754/avb200574010029
6. Kumar S., Sharma A. Cadmium toxicity: Effects on human reproduction and fertility. Rev. Environ. Health. 2019; 34(4): 327-38. https://doi.org/10.1515/reveh-2019-0016
7. Jeong E.M., Moon C.H., Kim C.S., Lee S.H., Baik E.J., Moon C.K., et al. Cadmium stimulates the expression of ICAM-1 via NF-kappaB activation in cerebrovascular endothelial cells. Biochem. Biophys. Res. Commun. 2004; 320(3): 887-92. https://doi.org/10.1016/j.bbrc.2004.05.218
8. Shagirtha K., Muthumani M., Prabu S.M. Melatonin abrogates cadmium induced oxidative stress related neurotoxicity in rats. Eur. Rev. Med. Pharmacol. Sci. 2011; 15(9): 1039-50.
9. Turley A.E., Zagorski J.W., Kennedy R.C., Freeborn R.A., Bursley J.K., Edwards J.R., et al. Chronic low-level cadmium exposure in rats affects cytokine production by activated T cells. Toxicol. Res. (Camb.) 2019; 8(2): 227-37. https://doi.org/10.1039/c8tx00194d
10. Unsal V., Dalkıran T., Çiçek M., Kölükçü E. The role of natural antioxidants against reactive oxygen species produced by cadmium toxicity: a review. Adv. Pharmaceut. Bull. 2020; 10(2): 184-202. https://doi.org/10.34172/apb.2020.023
11. Iftode A., Drăghici G.A., Macașoi I., Marcovici I., Coricovac D.E., Dragoi R., et al. Exposure to cadmium and copper triggers cytotoxic effects and epigenetic changes in human colorectal carcinoma HT-29 cells. Exp. Ther. Med. 2021; 21(1): 100. https://doi.org/10.3892/etm.2020.9532
12. Wang M., Wang J., Sun H., Han S., Feng S., Shi L., et al. Time-dependent toxicity of cadmium telluride quantum dots on liver and kidneys in mice: histopathological changes with elevated free cadmium ions and hydroxyl radicals. Int. J. Nanomedicine. 2016; 11: 2319-28. https://doi.org/10.2147/IJN.S103489
13. Martinez-Zamudio R., Ha HC Environmental epigenetics in metal exposure. Epigenetics. 2011; 6(7): 820-7. https://doi.org/10.4161/epi.6.7.16250
14. Buha A., Wallace D., Matovic V., Schweitzer A., Oluic B., Micic D., et al. Cadmium exposure as a putative risk factor for the development of pancreatic Cancer: three different lines of evidence. Biomed. Res. Int. 2017; 2017: 1981837. https://doi.org/10.1155/2017/1981837
15. Luevano J., Damodaran C. A review of molecular events of cadmium-induced carcinogenesis. J. Environ. Pathol. Toxicol. Oncol. 2014; 33(3): 183-94. https://doi.org/10.1615/jenvironpatholtoxicoloncol.2014011075
16. Eide D.J. The SLC39 family of metal ion transporters. Pflugers. Arch. 2004; 447(5): 796-800. https://doi.org/10.1016/j.mam.2012.05.011
17. Wang P., Zhang J., He S., Xiao B., Peng X. SLC39A1 contribute to malignant progression and have clinical prognostic impact in gliomas. Cancer Cell Int. 2020; 20(1): 573. https://doi.org/10.1186/s12935-020-01675-0
18. Kondo Y., Woo E.S., Michalska A.E., Choo K.H., Lazo J.S. Metallothionein null cells have increased sensitivity to anticancer drugs. Cancer Res. 1995; 55(10): 2021-3.
19. Janssen A.M., van Duijn W., Kubben F.J., Griffioen G., Lamers C.B., van Krieken J.H., et al. Prognostic significance of metallothionein in human gastrointestinal cancer. Clin. Cancer Res. 2002; 8(6): 1889-96.
20. Smith P.J., Wiltshire M., Furon E., Beattie J.H., Errington R.J. Impact of overexpression of metallothionein-1 on cell cycle progression and zinc toxicity. Am. J. Physiol. Cell. Physiol. 2008; 295(5): C1399-408. https://doi.org/10.1152/ajpcell.00342.2008
21. Thirumoorthy N., Manisenthil Kumar K.T., Shyam Sundar A., Panayappan L., Chatterjee M. Metallothionein: an overview. World J. Gastroenterol. 2007; 13(7): 993-6. https://doi.org/10.3748/wjg.v13.i7.993
22. Hosohata K., Mise N., Kayama F., Iwanaga K. Augmentation of cadmium-induced oxidative cytotoxicity by pioglitazone in renal tubular epithelial cells. Toxicol. Ind. Health. 2019; 35(8): 530-6. https://doi.org/10.1177/0748233719869548
23. Saedi S., Jafarzadeh Shirazi M.R., Totonchi M., Zamiri M.J., Derakhshanfar A. Effect of prepubertal exposure to CdCl2 on the liver, hematological, and biochemical parameters in female rats; an experimental study. Biol. Trace. Elem. Res. 2020; 194(2): 472-81. https://doi.org/10.1007/s12011-019-01800-9
24. Mężyńska M., Brzóska M.M. Review of polyphenol-rich products as potential protective and therapeutic factors against cadmium hepatotoxicity. J. Appl. Toxicol. 2019; 39(1): 117-45. https://doi.org/10.1002/jat.3709
25. Rikans L.E., Yamano T. Mechanisms of cadmium-mediated acute hepatotoxicity. J. Biochem. Mol. Toxicol. 2000; 14(2): 110-7. https://doi.org/10.1002/(sici)1099-0461(2000)14:2<110::aid-jbt7>3.0.co;2-j
26. Andjelkovic M., Buha Djordjevic A., Antonijevic E., Antonijevic B., Stanic M., Kotur-Stevuljevic J., et al. Toxic effect of acute cadmium and lead exposure in rat blood, liver, and kidney. Int. J. Environ. Res. Public Health. 2019; 16(2): 274. https://doi.org/10.3390/ijerph16020274
27. El-Refaiy A.I., Eissa F.I. Histopathology and cytotoxicity as biomarkers in treated rats with cadmium and some therapeutic agents. Saudi J. Biol. Sci. 2013; 20(3): 265-80. https://doi.org/10.1016/j.sjbs.2013.02.004
28. Kim B.M., Lee S.Y., Jeong I.H. Influence of squid liver powder on accumulation of cadmium in serum, kidney and liver of mice. Prev. Nutr. Food Sci. 2013; 18(1): 1-10. https://doi.org/10.3746/pnf.2013.18.1.001
29. Lu J., Jin T., Nordberg G., Nordberg M. Metallothionein gene expression in peripheral lymphocytes from cadmium-exposed workers. Cell Stress. Chaperones. 2001; 6(2): 97-104. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC434396/
30. Boonprasert K., Ruengweerayut R., Aunpad R., Satarug S., Na-Bangchang K. Expression of metallothionein isoforms in peripheral blood leukocytes from Thai population residing in cadmium-contaminated areas. Environ. Toxicol. Pharmacol. 2012; 34(3): 935-40. https://doi.org/10.1016/j.etap.2012.08.002
31. Yamada H., Koizumi S. Lymphocyte metallothionein-mRNA as a sensitive biomarker of cadmium exposure. Ind. Health. 2001; 39(1): 29-32. https://doi.org/10.2486/indhealth.39.29
32. Yang C.C., Lin C.I., Lee S.S., Wang C.L., Dai C.Y., Chuang H.Y. The association of blood lead levels and renal effects may be modified by genetic combinations of Metallothionein 1A 2A polymorphisms. Sci. Rep. 2020; 10(1): 9603. https://doi.org/10.1038/s41598-020-66645-y
33. McNeill R.V., Mason A.S., Hodson M.E., Catto J.W.F., Southgate J. Specificity of the Metallothionein-1 response by cadmium-exposed normal human urothelial cells. Int. J. Mol. Sci. 2019; 20(6): 1344. https://doi.org/10.3390/ijms20061344
34. Costello L.C., Franklin R.B. A comprehensive review of the role of zinc in normal prostate function and metabolism; and its implications in prostate cancer. Arch. Biochem. Biophys. 2016; 611: 100-12. https://doi.org/10.1016/j.abb.2016.04.014
35. Gaither L.A., Eide D.J. The human ZIP1 transporter mediates zinc uptake in human K562 erythroleukemia cells. J. Biol. Chem. 2001; 276(25): 22258-64. https://doi.org/10.1074/jbc.m101772200
36. Franklin R.B., Ma J., Zou J., Guan Z., Kukoyi B.I., Feng P., et al. Human ZIP1 is a major zinc uptake transporter for the accumulation of zinc in prostate cells. J. Inorg. Biochem. 2003; 96(2-3): 435-42. https://doi.org/10.1016/s0162-0134(03)00249-6
Review
For citations:
Ziatdinova M.M., Valova Ya.V., Mukhammadiyeva G.F., Fazlieva A.S., Karimov D.D., Kudoyarov E.R. Analysis of MT1 and ZIP1 gene expression in the liver of rats with chronic poisoning with cadmium chloride. Hygiene and Sanitation. 2021;100(11):1298-1302. (In Russ.) https://doi.org/10.47470/0016-9900-2021-100-11-1298-1302