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Evaluation of oxysterol levels of patients with silicosis by LC–MS/MS method

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Abstract

Silicosis is one of the prolonged and irreversible occupational diseases. Crystalline silica dust, which has been linked with silicosis, occurs in different industrial areas such as constructions, ceramic, quarry, and pottery. There are significant numbers of newly diagnosed cases every year in Turkey. Patients with silicosis suffer from inflammatory respiratory disorders and silicosis-related complications such as rheumatoid arthritis, systemic sclerosis, and vasculitis. Oxysterols are defined as 27-carbon intermediates or end products of cholesterol. They are also implicated in the etiology of disease states such as atherosclerosis, neurodegenerative, and inflammatory diseases. The aim of the study is to evaluate cholesterol oxidation products in the patients with silicosis and determination of sphingosine-1-phosphate (S1P) levels which is a sphingolipid metabolite. In addition to these parameters, it is aimed to determine the possible lipid peroxidation by different parameters. For this purpose, blood samples and urine were collected from 47 patients and 30 healthy individual with their consents. In order to evaluate oxysterols, 7-ketocholesterol and cholestan 3β,5α,6β-triol levels were measured by LC–MS/MS method. The measured levels of 7-KC were 0.101 ± 0.005 µmol/l in patient and 0.050 ± 0.003 µmol/l in control plasma samples. Triol levels were measured as 0.038 ± 0.005 µmol/l in patient group and 0.033 ± 0.004 µmol/l in control group (p < 0.001). In addition, lipid peroxidation products were measured by human-8-isoprostane, human-4-hydroxynonenal (4-HNE), and human malondialdehyde (MDA) ELISA kits. The measured levels of HNE in the patient and control groups were 735.14 ± 288.80 pg/ml and 595.72 ± 108.62 pg/ml in plasma and 606.02 + 118.23 pg/ml and 531.84 + 107.18 pg/ml in urine, respectively (p < 0.05). F2-iP results of patients and controls were 450.0 + 101.40 pg/dl and 386.9 + 112.7 pg/ml for urine and 432.7 ± 188,8 pg/dl and 321.9 ± 69.4 pg/dl for plasma, respectively (p < 0.05). MDA levels of plasma were measured as 44.1 ± 14.6 nmol/ml in the patient and 31.9 ± 10.5 nmol/ml in the control (p < 0.05). Levels of MDA for urine samples were 30.15 + 5.06 nmol/ml and 25.15 + 6.07 nmol/ml in patients and controls, respectively (p < 0.05). S1P levels were decreased in patients compared to control group (49.05 ± 10.87 and 67.57 ± 16.25, p < 0.001). The results not only indicate a correlation between cholesterol oxidation, lipid peroxidation, and silicosis, but also provide better understanding of the role of the lipids in the mechanism of this inflammatory disease.

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References

  1. Prasad B, Pandey J (2016) Serum copper and zinc level as biomarker for dust exposed lung diseases among coal miners. J Biodiv Environ Sci 8:65–74

    Google Scholar 

  2. Pandey JK, Agarwal D (2012) Biomarkers: a potential prognostic tool for silicosis. Indian J Occup environmental Med 16:101

    Article  Google Scholar 

  3. Karkhanis VS, Joshi J (2012) Combined pulmonary fibrosis and emphysema in a tyre industry worker. Lung India 29:273

    Article  Google Scholar 

  4. Akgun M, Araz O, Akkurt I, Eroglu A, Alper F, Saglam L, Mirici A, Gorguner M, Nemery B (2008) An epidemic of silicosis among former denim sandblasters. Eur Respir J 32:1295–1303

    Article  CAS  Google Scholar 

  5. Anlar HG, Bacanli M, İritaş S, Bal C, Kurt T, Tutkun E, Hinc Yilmaz O, Basaran N (2017) Effects of occupational silica exposure on oxidative stress and immune system parameters in ceramic workers in Turkey. J Toxicol Environ Health Part A 80:688–696

    Article  CAS  Google Scholar 

  6. Akgün M, Ergan B (2018) Silicosis in Turkey: is it an endless nightmare or is there still hope? Turkish Thorac J 19:89

    Article  Google Scholar 

  7. Archontogeorgis K, Steiropoulos P, Tzouvelekis A, Nena E, Bouros D (2012) Lung cancer and interstitial lung diseases: a systematic review. Pulm Med. https://doi.org/10.1155/2012/315918

    Article  PubMed  PubMed Central  Google Scholar 

  8. Sabuncuoğlu S, Öztaş Y (2014) Oxysterols and their metabolic roles beyond cholesterol: a reappraisal. Acta Med 45:75–79

    Google Scholar 

  9. Bargagli E, Olivieri C, Bennett D, Prasse A, Muller-Quernheim J, Rottoli P (2009) Oxidative stress in the pathogenesis of diffuse lung diseases: a review. Respir Med 103:1245–1256

    Article  CAS  Google Scholar 

  10. Vallyathan V, Leonard S, Kuppusamy P, Pack D, Chzhan M, Sanders SP, Zweir JL (1997) Oxidative stress in silicosis: evidence for the enhanced clearance of free radicals from whole lungs. Mol Cell Biochem 168:125–132

    Article  CAS  Google Scholar 

  11. Shi X, Mao Y, Daniel LN, Saffiotti U, Dalal NS, Vallyathan V (1994) Silica radical-induced DNA damage and lipid peroxidation. Environ Health Perspect 102(10):149–154. https://doi.org/10.1289/ehp.94102s10149

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Nardi J, Nascimento S, Goethel G, Gauer B, Sauer E, Fao N, Cestonaro L, Peruzzi C, Souza J, Garcia SC (2018) Inflammatory and oxidative stress parameters as potential early biomarkers for silicosis. Clin Chim Acta 484:305–313. https://doi.org/10.1016/j.cca.2018.05.045

    Article  CAS  PubMed  Google Scholar 

  13. Luu W, Sharpe LJ, Capell-Hattam I, Gelissen IC, Brown AJ (2016) Oxysterols: old tale, new twists. Annu Rev Pharmacol Toxicol 56:447–467

    Article  CAS  Google Scholar 

  14. Lütjohann D, Lizard G, Iuliano L (2017) Oxysterols: players in different metabolic leagues. J Steroid Biochem Mol Biol. https://doi.org/10.1016/j.jsbmb.2017.03.011

    Article  PubMed  Google Scholar 

  15. Iuliano L (2011) Pathways of cholesterol oxidation via non-enzymatic mechanisms. Chem Phys Lipid 164:457–468

    Article  CAS  Google Scholar 

  16. Niki E (2008) Lipid peroxidation products as oxidative stress biomarkers. BioFactors 34:171–180

    Article  CAS  Google Scholar 

  17. Maceyka M, Harikumar KB, Milstien S, Spiegel S (2012) Sphingosine-1-phosphate signaling and its role in disease. Trends Cell Biol 22:50–60. https://doi.org/10.1016/j.tcb.2011.09.003

    Article  CAS  PubMed  Google Scholar 

  18. Rimal B, Greenberg AK, Rom WN (2005) Basic pathogenetic mechanisms in silicosis: current understanding. Curr Opin Pulm Med 11:169–173

    Article  Google Scholar 

  19. Jiang X, Sidhu R, Porter FD, Yanjanin NM, Speak AO, te Vruchte DT, Platt FM, Fujiwara H, Scherrer DE, Zhang J (2011) A sensitive and specific LC-MS/MS method for rapid diagnosis of Niemann-Pick C1 disease from human plasma. J Lipid Res 52:1435–1445

    Article  CAS  Google Scholar 

  20. Zhang Y, Berka V, Song A, Sun K, Wang W, Zhang W, Ning C, Li C, Zhang Q, Bogdanov M, Alexander DC, Milburn MV, Ahmed MH, Lin H, Idowu M, Zhang J, Kato GJ, Abdulmalik OY, Zhang W, Dowhan W, Kellems RE, Zhang P, Jin J, Safo M, Tsai AL, Juneja HS, Xia Y (2014) Elevated sphingosine-1-phosphate promotes sickling and sickle cell disease progression. J Clin Invest 124:2750–2761. https://doi.org/10.1172/JCI74604

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Sari G, Simsek C, Gebesoglu B, Gulgosteren S, Uzmezoglu B and Celik D (2017) Accelerated silicosis in teflon-coated pan manufacturing: case report. C59. SILICOSIS, American Thoracic Society, pp. A5963–A5963

  22. Köksal N, Kahraman H (2011) Acute silicosis in teflon-coated pan manufacturing due to metal sandblasting. Int J Occup Environ Health 17:210–213

    Article  Google Scholar 

  23. Thomas CR, Kelley TR (2010) A brief review of silicosis in the United States. Environ Health Insights 4:EHI-S4628

    Article  Google Scholar 

  24. Peluso ME, Munnia A, Giese RW, Chellini E, Ceppi M, Capacci F (2015) Oxidatively damaged DNA in the nasal epithelium of workers occupationally exposed to silica dust in Tuscany region, Italy. Mutagenesis 30:519–525

    Article  CAS  Google Scholar 

  25. Wang Y, Yang G, Zhu Z, Liang D, Niu P, Gao A, Chen L, Tian L (2015) Effect of bone morphogenic protein-7 on the expression of epithelial–mesenchymal transition markers in silicosis model. Exp Mol Pathol 98:393–402

    Article  CAS  Google Scholar 

  26. Ikonen E (2008) Cellular cholesterol trafficking and compartmentalization. Nat Rev Mol Cell Biol 9:125–138. https://doi.org/10.1038/nrm2336

    Article  CAS  PubMed  Google Scholar 

  27. Berkowitz ML (2009) Detailed molecular dynamics simulations of model biological membranes containing cholesterol. Biochim Biophys Acta (BBA) 1788:86–96

    Article  CAS  Google Scholar 

  28. Kulig W, Cwiklik L, Jurkiewicz P, Rog T, Vattulainen I (2016) Cholesterol oxidation products and their biological importance. Chem Phys Lipid 199:144–160. https://doi.org/10.1016/j.chemphyslip.2016.03.001

    Article  CAS  Google Scholar 

  29. Zarrouk A, Vejux A, Mackrill J, O’Callaghan Y, Hammami M, O’Brien N, Lizard G (2014) Involvement of oxysterols in age-related diseases and ageing processes. Ageing Res Rev 18:148–162

    Article  CAS  Google Scholar 

  30. Cojocaru M, Niculescu T (1997) Study of plasma lipid peroxides in silicosis. Jugoslovenska Medicinska Biohemija-Yugoslav Med Biochem 16:25–27

    CAS  Google Scholar 

  31. Syslova K, Kacer P, Kuzma M, Najmanova V, Fenclova Z, Vlckova S, Lebedova J, Pelclova D (2009) Rapid and easy method for monitoring oxidative stress markers in body fluids of patients with asbestos or silica-induced lung diseases. J Chromatogr B 877:2477–2486. https://doi.org/10.1016/j.jchromb.2009.06.008

    Article  CAS  Google Scholar 

  32. Pelclova D, Fenclova Z, Syslova K, Vlckova S, Lebedova J, Pecha O, Belacek J, Navratil T, Kuzma M, Kacer P (2011) Oxidative stress markers in exhaled breath condensate in lung fibroses are not significantly affected by systemic diseases. Ind Health 49:746–754

    Article  CAS  Google Scholar 

  33. Arezzini B, Vecchio D, Signorini C, Stringa B, Gardi C (2018) F2-isoprostanes can mediate bleomycin-induced lung fibrosis. Free Radic Biol Med 115:1–9. https://doi.org/10.1016/j.freeradbiomed.2017.11.007

    Article  CAS  PubMed  Google Scholar 

  34. Montuschi P, Ciabattoni G, Paredi P, Pantelidis P, du Bois RM, Kharitonov SA, Barnes PJ (1998) 8-Isoprostane as a biomarker of oxidative stress in interstitial lung diseases. Am J Respir Crit Care Med 158:1524–1527. https://doi.org/10.1164/ajrccm.158.5.9803102

    Article  CAS  PubMed  Google Scholar 

  35. Muus P, Bonta IL, den Oudsten SA (1979) Plasma levels of malondialdehyde, a product of cyclo-oxygenase-dependent and independent lipid peroxidation in rheumatoid arthritis: a correlation with disease activity. Prostaglandins Med 2:63–65

    Article  CAS  Google Scholar 

  36. Bragt PC, Schenkelaars EP, Bonta IL (1979) Dissociation between prostaglandin and malondialdehyde formation in exudate and increased levels of malondialdehyde in plasma and liver during granulomatous inflammation in the rat. Prostaglandins Med 2:51–61

    Article  CAS  Google Scholar 

  37. Zhang H, Yin G, Jiang H, Zhang C (2013) High-dose N-acetylcysteine decreases silica-induced lung fibrosis in the rat. J Int Med Res 41:1179–1186. https://doi.org/10.1177/0300060513488503

    Article  CAS  PubMed  Google Scholar 

  38. Azari M, Ramazani B, Ali Mosavian M, Movahadi M, Salehpour S (2011) Serum malondialdehyde and urinary neopterin levels in glass sandblasters exposed to crystalline silica aerosols. Int J Occup Hyg 3(1):29–32

    Google Scholar 

  39. Anlar HG, Bacanli M, Iritas S, Bal C, Kurt T, Tutkun E, Hinc Yilmaz O, Basaran N (2017) Effects of occupational silica exposure on oxidative stress and immune system parameters in ceramic workers in Turkey. J Toxicol Environ Health A 80:688–696. https://doi.org/10.1080/15287394.2017.1286923

    Article  CAS  PubMed  Google Scholar 

  40. Esterbauer H, Schaur RJ, Zollner H (1991) Chemistry and biochemistry of 4-hydroxynonenal, malonaldehyde and related aldehydes. Free Radic Biol Med 11:81–128

    Article  CAS  Google Scholar 

  41. Barrera G, Pizzimenti S, Ciamporcero ES, Daga M, Ullio C, Arcaro A, Cetrangolo GP, Ferretti C, Dianzani C, Lepore A, Gentile F (2015) Role of 4-hydroxynonenal-protein adducts in human diseases. Antioxid Redox Signal 22:1681–1702. https://doi.org/10.1089/ars.2014.6166

    Article  CAS  PubMed  Google Scholar 

  42. Barrera G, Pizzimenti S, Daga M, Dianzani C, Arcaro A, Cetrangolo GP, Giordano G, Cucci MA, Graf M, Gentile F (2018) Lipid Peroxidation-derived aldehydes, 4-hydroxynonenal and malondialdehyde in aging-related disorders. Antioxidants (Basel). https://doi.org/10.3390/antiox7080102

    Article  Google Scholar 

  43. Nikolaidis MG, Kyparos A, Vrabas IS (2011) F2-isoprostane formation, measurement and interpretation: the role of exercise. Prog Lipid Res 50:89–103

    Article  CAS  Google Scholar 

  44. Czerska M, Zielinski M and Gromadzinska J (2015) Isoprostanes: a novel major group of oxidative stress markers Biochim Biophys Acta, 1851(4), 433–445.

    Google Scholar 

  45. Pelclova D, Fenclova Z, Kacer P, Navratil T, Kuzma M, Lebedova JK, Klusackova P (2007) 8-isoprostane and leukotrienes in exhaled breath condensate in Czech subjects with silicosis. Ind Health 45:766–774

    Article  Google Scholar 

  46. Björkhem I, Diczfalusy U, Lütjohann D (1999) Removal of cholesterol from extrahepatic sources by oxidative mechanisms. Curr Opin Lipidol 10:161–165

    Article  Google Scholar 

  47. Leonarduzzi G, Sottero B, Poli G (2002) Oxidized products of cholesterol: dietary and metabolic origin, and proatherosclerotic effects. J Nutr Biochem 13:700–710

    Article  CAS  Google Scholar 

  48. van Reyk DM, Brown AJ, Hult'en LM, Dean RT, Jessup W (2006) Oxysterols in biological systems: sources, metabolism and pathophysiological relevance. Redox Rep 11:255–262. https://doi.org/10.1179/135100006X155003

    Article  CAS  PubMed  Google Scholar 

  49. Jusakul A, Yongvanit P, Loilome W, Namwat N, Kuver R (2011) Mechanisms of oxysterol-induced carcinogenesis. Lipids Health Dis. https://doi.org/10.1186/1476-511x-10-44

    Article  PubMed  PubMed Central  Google Scholar 

  50. Poli G, Biasi F, Leonarduzzi G (2013) Oxysterols in the pathogenesis of major chronic diseases. Redox Biol 1:125–130

    Article  CAS  Google Scholar 

  51. Vejux A, Lizard G (2009) Cytotoxic effects of oxysterols associated with human diseases: Induction of cell death (apoptosis and/or oncosis), oxidative and inflammatory activities, and phospholipidosis. Mol Aspects Med 30:153–170

    Article  CAS  Google Scholar 

  52. Hinamoto N, Maeshima Y, Saito D, Yamasaki H, Tanabe K, Nasu T, Watatani H, Ujike H, Kinomura M, Sugiyama H (2014) Urinary and plasma levels of vasohibin-1 can predict renal functional deterioration in patients with renal disorders. PLoS ONE 9:e96932

    Article  Google Scholar 

  53. Nury T, Zarrouk A, Ragot K, Debbabi M, Riedinger J-M, Vejux A, Aubourg P, Lizard G (2017) 7-Ketocholesterol is increased in the plasma of X-ALD patients and induces peroxisomal modifications in microglial cells: Potential roles of 7-ketocholesterol in the pathophysiology of X-ALD. J Steroid Biochem Mol Biol 169:123–136

    Article  CAS  Google Scholar 

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Acknowledgements

The authors are thankful to all study participants. The authors would like to acknowledge all colleagues who assisted with this study. This study was supported by Hacettepe University Coordination Unit for Scientific Research Projects (GO 16/697-18).

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Authors and Affiliations

  1. Department of Toxicology, Faculty of Pharmacy, Hacettepe University, Sihhiye, Ankara, Turkey

    Neslihan Aksu, Tuğçe Çetin, Türkan Nadir Öziş & Suna Sabuncuoğlu

  2. Department of Medical Biochemistry, Faculty of Medicine, Hacettepe University, Ankara, Turkey

    Ahmet Yalçınkaya, İncilay Lay & Yeşim Öztaş

  3. Research and Development Center, University of Health Sciences, Ankara, Turkey

    Burcu Eser

  4. Faculty of Pharmaceutical Sciences, University of Iceland, Hofsvallagata 53, 107, Reykjavik, Iceland

    Afshin Samadi

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  1. Neslihan Aksu
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Aksu, N., Samadi, A., Yalçınkaya, A. et al. Evaluation of oxysterol levels of patients with silicosis by LC–MS/MS method. Mol Cell Biochem 467, 117–125 (2020). https://doi.org/10.1007/s11010-020-03706-w

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