Network-based Toxicogenomics Approach to Unraveling the Influence of Lead and Cadmium Mixture on the Development and Progression of Hypertension
Biotechnology Journal International, Volume 27, Issue 2,
Page 24-34
DOI:
10.9734/bji/2023/v27i2676
Abstract
Heavy metals, generally characterized by high densities and atomic weights, are ubiquitous in the environment and are a public health concern due to the several health issues they pose to humans. Of all heavy metals, lead and cadmium among others are known to be capable of inducing multiple health effects even at a low rate of exposure. Hypertension (HYP), a major cause of death and a risk factor for other cardiovascular diseases, is known to be caused by both lead and cadmium. While the mechanism underlying the development of HYP induced by independent exposure to lead and cadmium has been well studied, the mechanism underlying the induction and progression of HYP upon lead and cadmium co-exposure remains mildly explored. Hence, this study aimed to elucidate the mechanism using a toxicogenomic approach. The set of genes affected by both heavy metals was identified using the comparative toxicogenomics database (CTD) while HYP targets were retrieved from the Gene Cards database. The shared genes between the heavy metals and the disease were identified and subjected to further analysis. The results of our analysis revealed the signaling pathways that are dysregulated by lead and cadmium co-exposure while oxidative stress, inflammation, and endothelial dysfunction were revealed as processes pertinent to the induction and progression of HYP by lead and cadmium co-exposure. Biomarkers that could be used for prognosis evaluation were also identified. Ultimately, this study supports and advances the growing body of finding on the roles played by lead and cadmium co-exposure in inducing HYP.
- Hypertension (HYP)
- heavy metals
- lead
- cadmium
- signaling pathways
How to Cite
References
Tchounwou PB, Yedjou CG, Patlolla AK, Sutton DJ. Heavy Metal Toxicity and the Environment, in: 2012;133–164. DOI:https://doi.org/10.1007/978-3-7643-8340-4_6.
Seraj F, Rahman T. Heavy metals, metalloids, their toxic effect and living systems. Am J Plant Sci. 2018;09:2626–2643. DOI:https://doi.org/10.4236/ajps.2018.913191.
Mehrandish R, Rahimian A, Shahriary A. Heavy metals detoxification: A review of herbal compounds for chelation therapy in heavy metals toxicity. Journal of Herbmed Pharmacology. 2019;8:69–77.
DOI:https://doi.org/10.15171/jhp.2019.12.
Rana SVS. Perspectives in endocrine toxicity of heavy metals—a review. Biol Trace Elem Res. 2014;160:1–14.
DOI:https://doi.org/10.1007/s12011-014-0023-7.
Andjelkovic M, Buha Djordjevic A, Antonijevic E, Antonijevic B, Stanic M, Kotur-Stevuljevic J, Spasojevic-Kalimanovska V, Jovanovic M, Boricic N, Wallace D, Bulat Z. Toxic effect of acute cadmium and lead exposure in rat blood, liver, and kidney. Int J Environ Res Public Health. 2019;16:274. DOI:https://doi.org/10.3390/ijerph16020274.
Substance Priority List | ATSDR, (n.d.). Available:https://www.atsdr.cdc.gov/spl/#2019spl (accessed September 23, 2022).
Živančević K, Baralić K, Jorgovanović D, Buha Djordjević A, Ćurčić M, Antonijević Miljaković E, Antonijević B, Bulat Z, Đukić-Ćosić D. Elucidating the influence of environmentally relevant toxic metal mixture on molecular mechanisms involved in the development of neurodegenerative diseases: In silico toxicogenomic data-mining. Environ Res. 2021;194:110727. DOI:https://doi.org/10.1016/j.envres.2021.110727.
Zhou F, Xie J, Zhang S, Yin G, Gao Y, Zhang Y, Bo D, Li Z, Liu S, Feng C, Fan G. Lead, cadmium, arsenic, and mercury combined exposure disrupted synaptic homeostasis through activating the Snk-SPAR pathway. Ecotoxicol Environ Saf. 2018;163:674–684. DOI:https://doi.org/10.1016/j.ecoenv.2018.07.116.
Javorac D, Đorđević AB, Anđelković M, Tatović S, Baralić K, Antonijević E, Kotur-Stevuljević J, Đukić-Ćosić D, Antonijević B, Bulat Z. Redox and essential metal status in the brain of Wistar rats acutely exposed to a cadmium and lead mixture, Archives of Industrial Hygiene and Toxicology. 2020;71:197–204. DOI:https://doi.org/10.2478/aiht-2020-71-3425.
Chen X, Zhu G, Lei L, Jin T. The association between blood pressure and blood cadmium in a Chinese population living in cadmium polluted area. Environ Toxicol Pharmacol. 2013;36:595–599.
DOI:https://doi.org/10.1016/j.etap.2013.06.006.
Eum K, Lee M, Paek D. Cadmium in blood and hypertension. Science of The Total Environment. 2008;407:147–153. DOI:https://doi.org/10.1016/j.scitotenv.2008.08.037.
Robles HV, Romo E, Sanchez-Mendoza A, Rios A, Soto V, Avila-Casado MC, Medina A, Escalante B. Lead exposure effect on angiotensin II renal vasoconstriction. Hum Exp Toxicol. 2007;26:499–507.
DOI:https://doi.org/10.1177/0960327106077597.
Alghasham AA, Meki ARMA, Ismail HAS. Association of blood lead level with elevated blood pressure in hypertensive patients. Int J Health Sci (Qassim). 2011;517–27.
Davis AP, Grondin CJ, Johnson RJ, Sciaky D, McMorran R, Wieger:s J, Wiegers TC, Mattingly CJ. The comparative toxicogenomics database: update 2019. Nucleic Acids Res. 2019;47:D948–D954.
DOI:https://doi.org/10.1093/nar/gky868.
Davis AP, Murphy CG, Saraceni-Richards CA, Rosenstein MC, Wiegers TC, Mattingly CJ. Comparative toxicogenomics database: a knowledgebase and discovery tool for chemical-gene-disease networks, Nucleic Acids Res. 2009;37:D786–D792. DOI:https://doi.org/10.1093/nar/gkn580.
Davis AP, Murphy CG, Rosenstein MC, Wiegers TC, Mattingly CJ. The comparative toxicogenomics database facilitates identification and understanding of chemical-gene-disease associations: arsenic as a case study. BMC Med Genomics. 2008;1:48. DOI:https://doi.org /10.1186/1755-8794-1-48.
Stelzer G, Rosen N, Plaschkes I, Zimmerman S, Twik M, Fishilevich S, Stein T, Nudel R, Lieder I, Mazor Y, Kaplan S, Dahary D, Warshawsky D, Guan-Golan Y, Kohn A, Rappaport N, Safran M, Lancet D. Genecards suite: from gene data mining to disease genome sequence analyses. Curr Protoc Bioinformatics. 2016;54:1.30.1-1.30.33.
DOI:https://doi.org/10.1002/cpbi.5.
Szklarczyk D, Gable A, Lyon D, Junge A, Wyder S, Huerta-Cepas J, Simonovic M, Doncheva N, Morris J, Bork P, Jensen L, Mering C. Protein-protein association networks with increased coverage, supporting functional discovery in genome-wide experimental datasets. Nucleic Acids Reseach. 2019;47:D607–D613.
DOI:https://doi.org/10.1093/nar/gyk1131.
Ge S, Jung D, Yao R, Shiny GO. A graphical gene-set enrichment tool for animals and plants. Bioinformatics. 2020;36:2628–2629. DOI:https://doi.org/10.1093/bioinformatics/btz931.
Mani MS, Kunnathully V, Rao C, Kabekkodu SP, Joshi MB, D’Souza HS. Modifying effects of δ-Aminolevulinate dehydratase polymorphism on blood lead levels and ALAD activity, Toxicol Lett. 2018;295:351–356.
DOI:https://doi.org/10.1016/j.toxlet.2018.07.014.
Zhao Y. Structure and function of angiotensin converting enzyme and its inhibitors. Chin J Biotechnol. 2008;24:171–176.
DOI:https://doi.org/10.1016/S1872-2075(08)60007-2.
Pinheiro Júnior JEG, Moraes PZ, Rodriguez MD, Simões MR, Cibin F, Pinton S, Barbosa F, Junior FM, Peçanha, Vassallo DV, Miguel M, Wiggers GA. Cadmium exposure activates NADPH oxidase, renin–angiotensin system and cyclooxygenase 2 pathways in arteries, inducing hypertension and vascular damage. Toxicol Lett. 2020;333:80–89.
DOI:https://doi.org/10.1016/j.toxlet.2020.07.027
Broseghini-Filho GB, Almenara CCP, Vescovi MVA, de O. Faria T, Vassallo Dv, Angeli JK, Padilha AS. Acute cadmium exposure reduces the local angiotensin i converting enzyme activity and increases the tissue metal content. Biol Trace Elem Res. 2015;166:149–156. DOI:https://doi.org/10.1007/s12011-015-0250-6.
Carmignani M, Boscolo P, Poma A, Volpe AR. Kininergic system and arterial hypertension following chronic exposure to inorganic lead. Immunopharmacology. 1999;44:105–110. DOI:https://doi.org/10.1016/S0162-3109(99)00115-0.
Sharifi AM, Akbarloo N, Darabi R, Larijani B. Study of correlation between elevation of blood pressure and tissue ACE activity during development of hypertension in 1K1C rats. Vascul Pharmacol. 2004;41:15–20.
DOI:https://doi.org/10.1016/j.vph.2004.03.002.
Zhang H, Yan J, Niu J, Wang H, Li X. Association between lead and cadmium co-exposure and systemic immune inflammation in residents living near a mining and smelting area in NW China. Chemosphere. 2022;287:132190.
DOI:https://doi.org/10.1016/j.chemosphere.2021.132190.
Morcillo P, Esteban MÁ, Cuesta A. Heavy metals produce toxicity, oxidative stress and apoptosis in the marine teleost fish SAF-1 cell line. Chemosphere. 2016;144:225–233. DOI:https://doi.org/10.1016/j.chemosphere.2015.08.020.
Zhang Y, Huo X, Lu X, Zeng Z, Faas MM, Xu X. Exposure to multiple heavy metals associate with aberrant immune homeostasis and inflammatory activation in preschool children. Chemosphere. 2020;257:127257.
DOI:https://doi.org/10.1016/j.chemosphere.2020.127257.
Xiao L, Harrison DG. Inflammation in hypertension. Canadian Journal of Cardiology. 2020;36: 635–647.
DOI:https://doi.org/10.1016/j.cjca.2020.01.013.
Das SC, Al-Naemi HA. Cadmium toxicity: Oxidative stress, inflammation and tissue injury. Occupational Diseases and Environmental Medicine. 2019;07:144–163. DOI:https://doi.org/10.4236/odem.2019.74012.
Machoń-Grecka A, Dobrakowski M, Boroń M, Lisowska G, Kasperczyk A, Kasperczyk S. The influence of occupational chronic lead exposure on the levels of selected pro-inflammatory cytokines and angiogenic factors. Hum Exp Toxicol. 2017;36:467–473. DOI:https://doi.org/10.1177/0960327117703688.
Zhang H, Yan J, Niu J, Wang H, Li X. Association between lead and cadmium co-exposure and systemic immune inflammation in residents living near a mining and smelting area in NW China, Chemosphere. 2022;287:132190.
DOI:https://doi.org/10.1016/j.chemosphere.2021.132190.
Prasad K, Mishra M. Do advanced glycation end products and its receptor play a role in pathophysiology of hypertension? International Journal of Angiology. 2017;26:001–011. DOI:https://doi.org/10.1055/s-0037-1598183.
Mcnulty M, Mahmud A, Feely J. Advanced Glycation end-products and arterial stiffness in hypertension. Am J Hypertens. 2007;20:242–247. DOI:https://doi.org/10.1016/j.amjhyper.2006.08.009.
Jiao Y, Jiang H, Lu H, Yang Y, Zhang Y, Zhang K, Liu H. Deficiency of hypoxia inducible factor 1α promoted progression of diabetic nephropathy with hypertension. Exp Ther Med; 2018.
DOI:https://doi.org/10.3892/etm.2018.6621
McGettrick AF, O’Neill LAJ. The role of hif in immunity and inflammation. Cell Metab. 2020;32: 524–536.
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