Interplay Between Serum Zinc and Urinary Cadmium in Smokers: Potential Modulatory Effects on Serum CC16.
Article Sidebar
Main Article Content
Abstract
Background: Smoking-related metal exposure, especially cadmium, is associated with lung epithelial injury. CC16, or club cell protein, is a microprotein secreted by Clara cells that has many roles, including host defense and immune response, and emerged as a lung epithelial injury biomarker. Zinc is an essential trace element that might play a vital role in protection against cadmium toxicity. Objectives: This study was aimed to test the hypothesis that Cd from smoking is associated with club cell damage and intravascular leakage of CC16. Furthermore, examine the role of zinc in protection against it. Methodology: This study is a case-control study: Serum CC16, urinary Cd, and serum zinc were measured in two groups of smokers and in non-smokers (control group). Result: The serum levels of CC16 are significantly lower in smokers compared to non-smokers (p>0.0001). Also, there is a significant increase in the levels of urinary Cd in smokers compared to non-smokers (p = 0.0013). The levels of serum zinc are significantly lower in smokers compared to non-smokers (p = 0.0186). There is a significant positive correlation between serum zinc and urinary Cad (r = 0.3037 and p = 0.032). Conclusion: Clara cell protein (CC16) could be suggested as a marker for Cd inhaled toxin-induced cell damage; zinc could protect against the damage caused by Cd or modulate the damage caused by Cd through increasing the level of Cd in the urine.
Article Details
This work is licensed under a Creative Commons Attribution 4.0 International License.
References
Almuntashiri S, Zhu Y, Han Y, Wang X, Somanath PR, Zhang D. Club Cell Secreted Protein CC16: Potential Applications in Prognosis and Therapy for Pulmonary Diseases. J Clin Med. 2020;9(12). Epub 20201214. doi: 10.3390/jcm9124039. PubMed PMID: 33327505; PubMed Central PMCID: PMC7764992.
Hermans C, Knoops B, Wiedig M, Arsalane K, Toubeau G, Falmagne P, et al. Clara cell protein as a marker of Clara cell damage and bronchoalveolar blood barrier permeability. Eur Respir J. 1999;13(5):1014–21. doi: 10.1034/j.1399-3003.1999.13e14.x. PubMed PMID: 10414398.
Egron C, Labbé A, Rochette E, Mulliez A, Bernard A, Flore A. Urinary club cell protein 16 (CC16): Utility of its assay during acute bronchiolitis. Pediatr Pulmonol. 2020;55(2):490–5. Epub 20191126. doi: 10.1002/ppul.24584. PubMed PMID: 31770479; PubMed Central PMCID: PMC7167874.
Braido F, Riccio AM, Guerra L, Gamalero C, Zolezzi A, Tarantini F, et al. Clara cell 16 protein in COPD sputum: a marker of small airways damage? Respir Med. 2007;101(10):2119–24. Epub 20070710. doi: 10.1016/j.rmed.2007.05.023. PubMed PMID: 17624750.
Bernard AM, Gonzalez-Lorenzo JM, Siles E, Trujillano G, Lauwerys R. Early decrease of serum Clara cell protein in silica-exposed workers. Eur Respir J. 1994;7(11):1932–7. PubMed PMID: 7875262.
Dell'Omo M, Hermans C, Muzi G, Haufroid V, Bernard A, Carrieri P, et al. Serum Clara cell protein (CC16) in healthy young smokers. Biomarkers. 2000;5(2):158–64. doi: 10.1080/135475000230479. PubMed PMID: 23885953.
Park HY, Churg A, Wright JL, Li Y, Tam S, Man SF, et al. Club cell protein 16 and disease progression in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2013;188(12):1413–9. doi: 10.1164/rccm.201305-0892OC. PubMed PMID: 24245748; PubMed Central PMCID: PMC3917377.
Glushkova N, Smailova D, Namazbayeva Z, Mukasheva G, Zhamakurova A, Kuanyshkalieva A, et al. Prevalence of Smoking Various Tobacco Types in the Kazakhstani Adult Population in 2021: A Cross-Sectional Study. Int J Environ Res Public Health. 2023;20(2). Epub 20230113. doi: 10.3390/ijerph20021509. PubMed PMID: 36674264; PubMed Central PMCID: PMC9865649.
Lymperaki E, Makedou K, Iliadis S, Vagdatli E. Effects of acute cigarette smoking on total blood count and markers of oxidative stress in active and passive smokers. Hippokratia. 2015;19(4):293–7. PubMed PMID: 27688691; PubMed Central PMCID: PMC5033137.
Kim J, Song H, Lee J, Kim YJ, Chung HS, Yu JM, et al. Smoking and passive smoking increases mortality through mediation effect of cadmium exposure in the United States. Sci Rep. 2023;13(1):3878. Epub 20230308. doi: 10.1038/s41598-023-30988-z. PubMed PMID: 36890267; PubMed Central PMCID: PMC9995499.
Lin YS, Caffrey JL, Chang MH, Dowling N, Lin JW. Cigarette smoking, cadmium exposure, and zinc intake on obstructive lung disorder. Respir Res. 2010;11(1):53. Epub 20100509. doi: 10.1186/1465-9921-11-53. PubMed PMID: 20459696; PubMed Central PMCID: PMC2881897.
Matović V. Zinc, Copper, Or Magnesium Supplementation Against Cadmium Toxicity: Nova Science Publishers, Incorporated; 2010.
Yu HT, Zhen J, Leng JY, Cai L, Ji HL, Keller BB. Zinc as a countermeasure for cadmium toxicity. Acta Pharmacol Sin. 2021;42(3):340–6. Epub 20200413. doi: 10.1038/s41401-020-0396-4. PubMed PMID: 32284539; PubMed Central PMCID: PMC8027184.
Klaassen CD, Watkins JB. Casarett & Doull's essentials of toxicology: McGraw-Hill Medical New York; 2015.
Leignel V, Pillot L, Gerpe MS, Caurant F. Assessment of Knowledge on Metal Trace Element Concentrations and Metallothionein Biomarkers in Cetaceans. Toxics. 2023;11(5). Epub 20230512. doi: 10.3390/toxics11050454. PubMed PMID: 37235268; PubMed Central PMCID: PMC10224346.
Lowe NM, Woodhouse LR, Sutherland B, Shames DM, Burri BJ, Abrams SA, et al. Kinetic parameters and plasma zinc concentration correlate well with net loss and gain of zinc from men. The Journal of nutrition. 2004;134(9):2178–81.
Wessells KR, Jorgensen JM, Hess SY, Woodhouse LR, Peerson JM, Brown KH. Plasma Zinc Concentration Responds Rapidly to the Initiation and Discontinuation of Short-Term Zinc Supplementation in Healthy Men. The Journal of Nutrition. 2010;140(12):2128–33. doi: https://doi.org/10.3945/jn.110.122812.
Moody JR, Lindstrom RM. Selection and cleaning of plastic containers for storage of trace element samples. Analytical Chemistry. 1977;49(14):2264–7. doi: 10.1021/ac50022a039.
DeLon Hull RD, National Institute for Occupational S, Health. Metals in Urine: Method 8310. Cincinnati, Ohio, USA: NIOSH (U.S. Department of Health & Human Services), 1994 NIOSH 2003-154.
Onosaka S, Tanaka K, Cherian MG. Effects of cadmium and zinc on tissue levels of metallothionein. Environ Health Perspect. 1984;54:67–72. doi: 10.1289/ehp.845467. PubMed PMID: 6734572; PubMed Central PMCID: PMC1568161.
Inhorn MC, King L, Nriagu JO, Kobeissi L, Hammoud N, Awwad J, et al. Occupational and environmental exposures to heavy metals: risk factors for male infertility in Lebanon? Reprod Toxicol. 2008;25(2):203–12. Epub 20071030. doi: 10.1016/j.reprotox.2007.10.011. PubMed PMID: 18093800.
Afridi HI, Kazi TG, Kazi NG, Jamali MK, Arain MB, Sirajuddin, et al. Evaluation of cadmium, lead, nickel and zinc status in biological samples of smokers and nonsmokers hypertensive patients. J Hum Hypertens. 2010;24(1):34–43. doi: 10.1038/jhh.2009.39. PubMed PMID: 20010608; PubMed Central PMCID: PMC3011091.
Bonsnes RW, Taussky HH. ON THE COLORIMETRIC DETERMINATION OF CREATININE BY THE JAFFE REACTION. Journal of Biological Chemistry. 1945;158(3):581–91. doi: https://doi.org/10.1016/S0021-9258(19)51334-5.
Mason HJ, Williams NR, Morgan MG, Stevenson AJ, Armitage S. Influence of biological and analytical variation on urine measurements for monitoring exposure to cadmium. Occup Environ Med. 1998;55(2):132–7. doi: 10.1136/oem.55.2.132. PubMed PMID: 9614399; PubMed Central PMCID: PMC1757554.
Ściskalska M, Milnerowicz H. CC16 as an early marker of harmful effect of tobacco smoke exposure in women. Przegl Lek. 2016;73(10):690–3. PubMed PMID: 29688684.
Bernard A, Hermans C, Van Houte G. Transient increase of serum Clara cell protein (CC16) after exposure to smoke. Occup Environ Med. 1997;54(1):63–5. doi: 10.1136/oem.54.1.63. PubMed PMID: 9072037; PubMed Central PMCID: PMC1128638.
Robin M, Dong P, Hermans C, Bernard A, Bersten AD, Doyle IR. Serum levels of CC16, SP-A and SP-B reflect tobacco-smoke exposure in asymptomatic subjects. European Respiratory Journal.20(5):1152–61. doi: 10.1183/09031936.02.02042001.
Mannino DM, Holguin F, Greves HM, Savage-Brown A, Stock AL, Jones RL. Urinary cadmium levels predict lower lung function in current and former smokers: data from the Third National Health and Nutrition Examination Survey. Thorax. 2004;59(3):194–8. doi: 10.1136/thorax.2003.012054. PubMed PMID: 14985551; PubMed Central PMCID: PMC1746977.
Ferraro PM, Costanzi S, Naticchia A, Sturniolo A, Gambaro G. Low level exposure to cadmium increases the risk of chronic kidney disease: analysis of the NHANES 1999-2006. BMC Public Health. 2010;10(1):304. doi: 10.1186/1471-2458-10-304.
Rokadia HK, Agarwal S. Serum heavy metals and obstructive lung disease: results from the National Health and Nutrition Examination Survey. Chest. 2013;143(2):388–97. doi: 10.1378/chest.12-0595. PubMed PMID: 22911427.
Skalny AV, Serebryansky EP, Korobeinikova TV, Tsatsakis A, Vardavas C, Paoliello MMB, et al. Smoking is associated with altered serum and hair essential metal and metalloid levels in women. Food Chem Toxicol. 2022;167:113249. Epub 20220618. doi: 10.1016/j.fct.2022.113249. PubMed PMID: 35728725.
Theint Hlaing ZT. Relationship between Oxidative Stress, Serum Zinc Level and Systemic Arterial Blood Pressure in Smokers and Non-smokers. International Journal of Clinical and Experimental Physiology. 2019;6(3):100–3. doi: 10.5530/ijcep.2019.6.3.27.
Vance TM, Chun OK. Zinc Intake Is Associated with Lower Cadmium Burden in U.S. Adults. J Nutr. 2015;145(12):2741–8. Epub 20151021. doi: 10.3945/jn.115.223099. PubMed PMID: 26491124.
Kershaw CJ, Brown NL, Hobman JL. Zinc dependence of zinT (yodA) mutants and binding of zinc, cadmium and mercury by ZinT. Biochemical and biophysical research communications. 2007;364(1):66–71.
Liu Z, Li H, Soleimani M, Girijashanker K, Reed JM, He L, et al. Cd2+ versus Zn2+ uptake by the ZIP8 HCO3--dependent symporter: kinetics, electrogenicity and trafficking. Biochemical and biophysical research communications. 2008;365(4):814–20.
Barbier O, Jacquillet G, Tauc M, Poujeol P, Cougnon M. Acute study of interaction among cadmium, calcium, and zinc transport along the rat nephron in vivo. American Journal of Physiology-Renal Physiology. 2004;287(5):F1067–F75.
Lin Y-S, Ho W-C, Caffrey JL, Sonawane B. Low serum zinc is associated with elevated risk of cadmium nephrotoxicity. Environmental research. 2014;134:33–8.
Bao S, Knoell DL. Zinc modulates cytokine-induced lung epithelial cell barrier permeability. Am J Physiol Lung Cell Mol Physiol. 2006;291(6):L1132–41. Epub 20060714. doi: 10.1152/ajplung.00207.2006. PubMed PMID: 16844947.
Gribben KC, Poole JA, Nelson AJ, Farazi PA, Wichman CS, Heires AJ, et al. Relationships of serum CC16 levels with smoking status and lung function in COPD. Respir Res. 2022;23(1):247. Epub 20220916. doi: 10.1186/s12931-022-02158-8. PubMed PMID: 36114505; PubMed Central PMCID: PMC9479424.
Zhu L, Di PY, Wu R, Pinkerton KE, Chen Y. Repression of CC16 by cigarette smoke (CS) exposure. PLoS One. 2015;10(1):e0116159. Epub 20150130. doi: 10.1371/journal.pone.0116159. PubMed PMID: 25635997; PubMed Central PMCID: PMC4312097.