DOI QR코드

DOI QR Code

Identification of acrolein as a novel diagnostic odor biomarker for 1,2,3-trichloropropane-induced hepatotoxicity in Sprague Dawley rats

  • Ji Eun Kim (Department of Biomaterials Science (BK21 FOUR Program)/Life and Industry Convergence Research Institute/Laboratory Animals Resources Center, College of Natural Resources and Life Science, Pusan National University) ;
  • Tae Ryeol Kim (Department of Biomaterials Science (BK21 FOUR Program)/Life and Industry Convergence Research Institute/Laboratory Animals Resources Center, College of Natural Resources and Life Science, Pusan National University) ;
  • Hee Jin Song (Department of Biomaterials Science (BK21 FOUR Program)/Life and Industry Convergence Research Institute/Laboratory Animals Resources Center, College of Natural Resources and Life Science, Pusan National University) ;
  • Yu Jeong Roh (Department of Biomaterials Science (BK21 FOUR Program)/Life and Industry Convergence Research Institute/Laboratory Animals Resources Center, College of Natural Resources and Life Science, Pusan National University) ;
  • Ayun Seol (Department of Biomaterials Science (BK21 FOUR Program)/Life and Industry Convergence Research Institute/Laboratory Animals Resources Center, College of Natural Resources and Life Science, Pusan National University) ;
  • Ki Ho Park (Department of Biomaterials Science (BK21 FOUR Program)/Life and Industry Convergence Research Institute/Laboratory Animals Resources Center, College of Natural Resources and Life Science, Pusan National University) ;
  • Eun Seo Park (Department of Biomaterials Science (BK21 FOUR Program)/Life and Industry Convergence Research Institute/Laboratory Animals Resources Center, College of Natural Resources and Life Science, Pusan National University) ;
  • Kyeong Seon Min (Department of Biomaterials Science (BK21 FOUR Program)/Life and Industry Convergence Research Institute/Laboratory Animals Resources Center, College of Natural Resources and Life Science, Pusan National University) ;
  • Kyu‑Bong Kim (College of Pharmacy, Dankook University) ;
  • Seung Jun Kwack (Department of Bio Health Science, College of Natural Science, Changwon National University) ;
  • Young Suk Jung (Department of Pharmacy, College of Pharmacy, Research Institute for Drug Development, Pusan National University) ;
  • Dae Youn Hwang (Department of Biomaterials Science (BK21 FOUR Program)/Life and Industry Convergence Research Institute/Laboratory Animals Resources Center, College of Natural Resources and Life Science, Pusan National University)
  • Received : 2023.11.21
  • Accepted : 2024.06.26
  • Published : 2024.10.15

Abstract

Body odor is considered a diagnostic indicator of various infectious and chronic diseases. But, few studies have examined the odor markers for various toxic effects in the mammalian system. This study attempted to identify the novel diagnostic odor biomarkers for chemical-induced hepatotoxicity in animals. The changes in the concentration of odors were analyzed in the urine of Sprague Dawley (SD) rats treated with two dosages (100 or 200 mg/kg) of 1,2,3-trichloropropane (TCP) using gas chromatography-mass spectrometry (GC-MS). The TCP treatment induced significant toxicity, including a decrease in body weight, an increase in serum biochemical factors, and histopathological changes in the liver of SD rats. During this hepatotoxicity, the concentrations of six odors (ethyl alcohol, acrolein (2-propenal), methanesulfonyl chloride, methyl ethyl ketone, cyclotrisiloxane, and 2-heptanone) in urine changed significantly after the TCP treatment. Among them, acrolein, an acrid and pungent compound, showed the highest rate of increase in the TCP-treated group compared to the Vehicle-treated group. In addition, this increase in acrolein was accompanied by enhanced spermine oxidase (SMOX) expression, an acrolein metabolic enzyme, and the increased level of IL-6 transcription as a regulator factor that induces SMOX production. The correlation between acrolein and other parameters was conformed using correlagram analyses. These results provide scientific evidence that acrolein have potential as a novel diagnostic odor biomarker for TCP-induced hepatotoxicity.

Keywords

Acknowledgement

The authors thank Jin Hyang Hwang, the animal technician, for directing animal use and care at the Laboratory Animal Resources Center at Pusan National University.

References

  1. Shirasu M, Touhara K (2011) The scent of disease: volatile organic compounds of the human body related to disease and disorder. J Biochem 150:257-266. https://doi.org/10.1093/jb/mvr090
  2. Hakim M, Broza YY, Barash O, Peled N, Phillips M, Amann A, Haick H (2012) Volatile organic compounds of lung cancer and possible biochemical pathways. Chem Rev 112:5949-5966. https://doi.org/10.1021/cr300174a
  3. Sharma A, Kumar R, Varadwaj P (2023) Smelling the disease: diagnostic potential of breath analysis. Mol Diag Ther 27:321-347. https://doi.org/10.1007/s40291-023-00640-7
  4. Broza YY, Vishinkin R, Barash O, Nakhleh MK, Haick H (2018) Synergy between nanomaterials and volatile organic compounds for non-invasive medical evaluation. Chem Soc Rev 47:4781-4859. https://doi.org/10.1039/c8cs00317c
  5. Penn DJ, Oberzaucher E, Grammer K, Fischer G, Soini HA, Wiesler D, Novotny MV, Dixon SJ, Xu Y, Brereton RG (2007) Individual and gender fngerprints in human body odour. J R Soc Interface 4:331-340. https://doi.org/10.1098/rsif.2006.0182
  6. Smeets MAM, Rosing EAE, Jacobs DM, van Velzen E, Koek JH, Blonk C, Gortemaker I, Eidhof MB, Markovitch B, de Groot J, Semin GR (2020) Chemical fngerprints of emotional body odor. Metabolites 10:84. https://doi.org/10.3390/metabo10030084
  7. Mazzatenta A, Giulio CD, Pokorski M (2013) Pathologies currently identified by exhaled biomarkers. Respir Physiol Neurobiol 187:128-134. https://doi.org/10.1016/j.resp.2013.02.016
  8. Garner CE, Smith S, Bardhan PK, Ratclife NM, Probert CS (2009) A pilot study of faecal volatile organic compounds in faeces from cholera patients in Bangladesh to determine their utility in disease diagnosis. Trans R Soc Trop Med Hyg 103:1171-1173. https://doi.org/10.1016/j.trstmh.2009.02.004
  9. Shirasu M, Nagai S, Hayashi R, Ochiai A, Touhara K (2009) Dimethyl trisulfide as a characteristic odor associated with fungating cancer wounds. Biosci Biotechnol Biochem 73:2117-2120. https://doi.org/10.1271/bbb.90229
  10. Dankert J, Holloway Y, Bouma J, van der Werf J, Wolthers BG (1981) Metronidazole in smelly gynaecological tumours. Lancet 2:1295. https://doi.org/10.1016/s0140-6736(81)91539-7
  11. Pavlou AK, Turner AP (2000) Sniffing out the truth: clinical diagnosis using the electronic nose. Clin Chem Lab Med 38:99-112. https://doi.org/10.1515/CCLM.2000.016
  12. Burke DG, Halpern B, Malegan D, McCairns E, Danks D, Schlesinger P, Wilken B (1983) Profiles of urinary volatiles from metabolic disorders characterized by unusual odors. Clin Chem 29:1834-1838
  13. Centerwall SA, Centerwall WR (2000) The discovery of phenylketonuria: the story of a young couple, two retarded children, and a scientist. Pediatrics 105:89-103. https://doi.org/10.1542/peds.105.1.89
  14. Smith AJ, Strang LB (1958) An inborn error of metabolism with the urinary excretion of alpha-hydroxy-butyric acid and phenylpyruvic acid. Arch Dis Child 33:1091-1310. https://doi.org/10.1136/adc.33.168.109
  15. Humbert JA, Hammond KB, Hathaway WE (1970) Trimethylaminuria: the fish-odour syndrome. Lancet 2:770771. https://doi.org/10.1016/S0140-6736(70)90241-2
  16. Liebich HM (1983) Analysis of acidic metabolites by capillary column GC and GC/MS. J High Resolut Chromatogr Chromatogr Commun 6:640-650. https://doi.org/10.1002/jhrc.1240061202
  17. Phillips M, Gleeson K, Hughes JM, Greenberg J, Cataneo RN, Baker L, McVay WP (1999) Volatile organic compounds in breath as markers of lung cancer: a cross-sectional study. Lancet 353:1930-1933. https://doi.org/10.1016/S0140-6736(98)07552-7
  18. Olopade CO, Zakkar M, Swedler WI, Rubinstein I (1997) Exhaled pentane levels in acute asthma. Chest 111:862-865. https://doi.org/10.1378/chest.111.4.862
  19. Smith JN, Wang J, Lin YH, Klohe EM, Timchalk C (2012) Pharmacokinetics and pharmacodynamics of chlorpyrifos and 3,5,6-trichloro-2-pyridinol in rat saliva after chlorpyrifos administration. Toxicol Sci 130:245-256. https://doi.org/10.1093/toxsci/kfs251
  20. Agency for Toxic Substances and Disease Registry (1992) Toxicological profle for 1,2,3-trichloropropane (report). U.S. CDC. https://semspub.epa.gov/work/09/1117960.pdf
  21. Liu YH, Shen DY, Zhong DL, Mo RH, Ni ZL, Tang FB (2014) Time-dependent movement and distribution of chlorpyrifos and its metabolism in bamboo forest under soil surface mulching. J Agric Food Chem 62:6565-6570. https://doi.org/10.1021/jf501540e
  22. Ur Rahman HU, Asghar W, Nazir W, Sandhu MA, Ahmed A, Khalid N (2021) A comprehensive review on chlorpyrifos toxicity with special reference to endocrine disruption: evidence of mechanisms, exposures and mitigation strategies. Sci Total Environ 755:142649. https://doi.org/10.1016/j.scitotenv.2020.142649
  23. Cooke M (2009) Emerging contaminant-1,2,3-trichloropropane (TCP) (report). United States EPA. https://nepis.epa.gov/Exe/ZyNET.exe
  24. Liu X, Qiu Z, Shen W, Pemg X (2012) The clinical analysis of 18 cases with acute trichloropropane poisoning. Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi 30:307-309
  25. Irwin RD, Haseman JK, Eustis SL (1995) 1,2,3-Trichloropropane: a multisite carcinogen in rats and mice. Fundam Appl Toxicol 25:241-252. https://doi.org/10.1006/faat.1995.1060
  26. Volp RF, Sipes IG, Falcoz C, Carter DE, Gross JF (1984) Disposition of 1,2,3-trichloropropane in the fscher 344 rat: conventional and physiological pharmacokinetics. Toxicol Appl Pharmacol 75:8-17. https://doi.org/10.1016/0041-008x(84)90070-x
  27. La DK, Schoonhoven R, Ito N, Swenberg JA (1996) The effects of exposure route on DNA adduct formation and cellular proliferation by 1,2,3-trichloropropane. Toxicol Appl Pharmacol 140:108-114. https://doi.org/10.1006/taap.1996.0203
  28. Mahmood NA, Overstreet D, Burka LT (1991) Comparative disposition and metabolism of 1,2,3-trichloropropane in rats and mice. Drug Metab Dispos 19:411-418
  29. National Toxicology Program (1993) NTP toxicology and carcinogenesis of 1,2,3-Trichloropropane (CAS No. 96-18-4) in F344/N rats and B6C3F1 mice (Gavage Studies). Natl Toxicol Program Tech Rep Ser 384:1-348. https://ntp.niehs.nih.gov/go/tr384abs
  30. Chen S, Mahadevan V, Zieve L (1970) Volatile fatty acids in the breath of patients with cirrhosis of the liver. J Lab Clin Med 75:622-627
  31. Hisamura M (1979) Quantitative analysis of methyl mercaptan and dimethyl sulfide in human expired alveolar gas and its clinical application: study in normal subjects and patients with liver diseases (author's transl). Nippon Naika Gakkai Zasshi 68:1284-1292. https://doi.org/10.2169/naika.68.1284
  32. Kaji H, Hisamura M, Saito N, Murao M (1978) Evaluation of volatile sulfur compounds in the expired alveolar gas in patients with liver cirrhosis. Clin Chim Acta 85:279-284. https://doi.org/10.1016/0009-8981(78)90305-4
  33. Sehnert SS, Jiang L, Burdick JF (2002) Risby TH (2002) Breath biomarkers for detection of human liver diseases: preliminary study. Biomarkers 7:174-187. https://doi.org/10.1080/13547500110118184
  34. Solga SF, Alkhuraishe A, Cope K, Tabech A, Clark JM, Torbenson M, Schwartz P, Magnuson T, Diehl AM, Risby TH (2006) Breath biomarkers and non-alcoholic fatty liver disease: preliminary observations. Biomarkers 11:174-183. https://doi.org/10.1080/13547500500421070
  35. Netzer M, Millonig G, Osl M, Pfeifer B, Praun S, Villinger J, Vogel W, Baumgartner C (2009) A new ensemble-based algorithm for identifying breath gas marker candidates in liver disease using ion molecule reaction mass spectrometry. Bioinformatics 25:941-947. https://doi.org/10.1093/bioinformatics/btp093
  36. Dadamio J, Van den Velde S, Laleman W, Hee PV, Coucke W, Nevens F, Quirynen M (2012) Breath biomarkers of liver cirrhosis. J Chromatogr B Anal Technol Biomed Life Sci 905:17-22. https://doi.org/10.1016/j.jchromb.2012.07.025
  37. Letteron P, Duchatelle V, Berson A, Fromenty B, Fisch C, Degott C, Benhamou JP, Pressayre D (1993) Increased ethane exhalation, an in vivo index of lipid peroxidation, in alcohol-abusers. Gut 34:409-414. https://doi.org/10.1136/gut.34.3.409
  38. Rehman HU (1999) Fish odor syndrome. Postgrad Med J 75:451-452. https://doi.org/10.1136/pgmj.75.886.451
  39. Cashman JR, Camp K, Fakharzadeh SS, Fennessey PV, Hines RN, Mamer OA, Mitchell SC, Nguyen GP, Schlenk D, Smith RL, Tjoa SS, Williams DE, Yannicelli S (2003) Biochemical and clinical aspects of the human favin-containing monooxygenase form 3 (FMO3) related to trimethylaminuria. Curr Drug Metab 4:151-170. https://doi.org/10.2174/1389200033489505
  40. Kim JE, Choi YJ, Lee SJ, Gong JE, Seong JE, Park SH, Hwang DY (2022) Evaluation of deodorizing effects of Saccharina japonica in 10-month-mld ICR mice using a novel odor marker associated with aging. Evid Based Complement Alternat Med 2022:1410144. https://doi.org/10.1155/2022/1410144
  41. Kim JE, Choi YJ, Lee SJ, Gong JE, Lee YJ, Sung JE, Jung YS, Lee HS, Hong JT, Hwang DY (2021) Antioxidant activity and laxative efects of tannin-enriched extract of Ecklonia cava in loperamide-induced constipation of SD rats. PLoS One 16:e0246363. https://doi.org/10.1371/journal.pone.0246363
  42. Brodzik K, Faber J, Gotda-Kopek A, Lomankiewicz D (2016) Impact of multisource VOC emission on in-vehicle air quality: test chamber simulation. IOP Conf Ser Mater Sci Eng 148:012033. https://doi.org/10.1088/1757-899x/148/1/012033
  43. Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2 (-Delta Delta C(T)) method. Methods 25:402-408. https://doi.org/10.1006/meth.2001.1262
  44. Beauchamp RO Jr, Andjelkovich DA, Kligerman AD, Morgan KT, Heck HD (1985) A critical review of the literature on acrolein toxicity. Crit Rev Toxicol 14:309-380. https://doi.org/10.3109/10408448509037461
  45. Ernstgard L, Dwivedi AM, Lundstrom JN, Johanson G (2017) Measures of odor and lateralization thresholds of acrolein, crotonaldehyde, and hexanal using a novel vapor delivery technique. PLoS One 12:e0185479. https://doi.org/10.1371/journal.pone.0185479
  46. Liddell K (1976) Smell as a diagnostic marker. Postgrad Med J 52:136-138. https://doi.org/10.1136/pgmj.52.605.136
  47. Rosenblatt Y, Phan P, Desandre P, Lobon L, Hsu C (2000) Diagnostic odor recognition. Acad Emerg Med 7:1168-1169 https://doi.org/10.1111/j.1553-2712.1997.tb03704.x
  48. Penn D, Potts WK (1998) Chemical signals and parasite-mediated sexual selection. Trends Ecol Evol 13:391-396. https://doi.org/10.1016/s0169-5347(98)01473-6
  49. Wang J, Zhou G, Chen C, Yu H, Wang T, Ma Y, Jia G, Gao Y, Li B, Sun J, Li Y, Jiao F, Zhao Y, Chai Z (2007) Acute toxicity and biodistribution of diferent sized titanium dioxide particles in mice after oral administration. Toxicol Lett 168:176-185. https://doi.org/10.1016/j.toxlet.2006.12.001
  50. Bergmeyer HU (1974) Methods of enzymatic analysis, 2nd edn. Academic Press, Weinheim, p 20
  51. Yun TK, Lee YS, Kwon HY, Choi KJ (1996) Saponin contents and anticarcinogenic efects of ginseng depending on types and ages in mice. Zhongguo Yao Li Xue Bao 17:293-298
  52. You AS, Jeong MH, Park KH, Kim BS, Lee JB, Choi JH, Kwon OK, Kim JH (2007) Efect on antioxidant function of onion to reduce pesticides toxicity. Korean J Pestic Sci 11:222-229. https://koreascience.kr/article/JAKO200709906340883.pdf
  53. Losser MR, Payen D (1996) Mechanisms of liver damage. Semin Liver Dis 16:357-367. https://doi.org/10.1055/s-2007-1007249
  54. Jarrar BM, Taib NT (2012) Histological and histochemical alterations in the liver induced by lead chronic toxicity. Saudi J Biol Sci 19:203-210. https://doi.org/10.1016/j.sjbs.2011.12.005
  55. Ziaolhagh SJ, Ardakanizadeh M, Kaveh A, Yahyaei B (2023) Liver tissue changes induced by biological and chemical silver nanoparticles in trained male Wistar rats. J Trace Elem Med Biol 79:127253. https://doi.org/10.1016/j.jtemb.2023.127253
  56. Merrick BA, Robinson M, Condie LW (1991) Cardiopathic effect of 1,2,3-trichloropropane after subacute and subchronic exposure in rats. J Appl Toxicol 11:179-187. https://doi.org/10.1002/jat.2550110305
  57. Villeneuve DC, Chu I, Secours VE, Cote MG, Plaa GL, Valli VE (1985) Results of a 90-day toxicity study on 1,2,3- and 1,1,2-trichloropropane and administered via the drinking water. Sci Total Environ 47:421-426. https://doi.org/10.1016/0048-9697(85)90346-8
  58. Behrman AD, Goertemoeller S (2009) What is that smell? J Emerg Nurs 35:263-264. https://doi.org/10.1016/j.jen.2009.02.013
  59. Shertzer HG (2001) Organic sulfur compounds. In: Bingham E, Cohrssen B, Powell CH (eds) Patty's toxicology, vol 7. Wiley, New York, pp 746-747
  60. Committee on Acute Exposure Guideline Levels (2013) Methanesulfonyl chloride: acute exposure guideline levels (report no. PWT 45/861670). AEGL 14. https://www.ncbi.nlm.nih.gov/books/NBK201481/
  61. Krasavage WJ, O'Donoghue JL, Di Vincenzo GD (1982) Methyl isobutyl ketone. In: Clayton, Clayton (eds) Patty's industrial hygiene and toxicology, vol 2e, 4747. John Wily & Son, New York
  62. Wang R, Moody RP, Koniecki D, Zhu J (2009) Low molecular weight cyclic volatile methylsiloxanes in cosmetic products sold in Canada: implication for dermal exposure. Environ Int 35:900-904. https://doi.org/10.1016/j.envint.2009.03.009
  63. Fromme H, Debiak M, Sagunski H, Rohl C, Kraft M, Kolossa-Gehring M (2019) The German approach to regulate indoor air contaminants. Int J Hyg Environ Health 222:347-354. https://doi.org/10.1016/j.ijheh.2018.12.012
  64. Denawaka CJ, Fowlis IA, Dean JR (2016) Source, impact and removal of malodour from soiled clothing. J Chromatogr A 1438:216-225. https://doi.org/10.1016/j.chroma.2016.02.037
  65. Perbellini L, Brugnone F, Cocheo V, De Rosa E, Bartolucci GB (1986) Identification of the n-heptane metabolites in rat and human urine. Arch Toxicol 58:229-234. https://doi.org/10.1007/BF00297111
  66. Walker V, Mills GA (2001) Urine 4-heptanone: a beta-oxidation product of 2-ethylhexanoic acid from plasticisers. Clin Chim Acta 306:51-61. https://doi.org/10.1016/s0009-8981(01)00390-4
  67. Weber-Tschopp A, Fischer T, Gierer R, Grandjean E (1977) Experimentally induced irritating effects of acrolein on men (author's transl). Int Arch Occup Environ Health 40:117-130. https://doi.org/10.1007/BF00575156
  68. Arntz D, Fischer A, Hopp M, Jacobi S, Sauer J, Ohara T, Sato T, Shimizu N, Schwind H (2007) Acrolein and methacrolein. In: Ullmann's encyclopedia of industrial chemistry. Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim. https://doi.org/10.1002/14356007.a01_149.pub2
  69. Paci A, Rieutord A, Guillaume D, Traore F, Ropenga J, Husson HP, Brion F (2000) Quantitative high-performance liquid chromatography chromatographic determination of acrolein in plasma after derivatization with Luminarin 3. J Chromatogr B Biomed Sci Appl 739:239-246. https://doi.org/10.1016/s0378-4347(99)00485-5
  70. Engels C, Schwab C, Zhang J, Stevens MJA, Bieri C, Ebert MO, McNeill K, Sturla SJ, Lacroix C (2016) Acrolein contributes strongly to antimicrobial and heterocyclic amine transformation activities of reuterin. Sci Rep 6:36246. https://doi.org/10.1038/srep36246
  71. Stevens JF, Maier CS (2008) Acrolein: Sources, metabolism, and biomolecular interactions relevant to human health and disease. Mol Nutr Food Res 52:7-25. https://doi.org/10.1002/mnfr.200700412
  72. Sharmin S, Sakata K, Kashiwagi K, Ueda S, Iwasaki S, Shirahata A, Igarashi K (2001) Polyamine cytotoxicity in the presence of bovine serum amine oxidase. Biochem Biophys Res Commun 282:228-235. https://doi.org/10.1006/bbrc.2001.4569
  73. Anderson MM, Hazen SL, Hsu FF, Heinecke JW (1997) Human neutrophils employ the myeloperoxidase-hydrogen peroxide-chloride system to convert hydroxy-amino acids into glycolaldehyde, 2-hydroxypropanal, and acrolein: a mechanism for the generation of highly reactive alpha-hydroxy and alpha, beta-unsaturated aldehydes by phagocytes at sites of infammation. J Clin Invest 99:424-432. https://doi.org/10.1172/JCI119176
  74. Cervelli M, Bellavia G, Fratini E, Amendola R, Polticelli F, Barba M, Federico R, Signore F, Gucciardo G, Grillo R, Woster PM, Casero RA Jr, Mariottini P (2010) Spermine oxidase (SMO) activity in breast tumor tissues and biochemical analysis of the anticancer spermine analogues BENSpm and CPENSpm. BMC Cancer 10:555. https://doi.org/10.1186/1471-2407-10-555
  75. Cervelli M, Polticelli F, Federico R, Mariottini P (2003) Heterologous expression and characterization of mouse spermine oxidase. J Biol Chem 278:5271-5276. https://doi.org/10.1074/jbc.M207888200
  76. Ceci R, Duranti G, Leonetti A, Pietropaoli S, Spinozzi F, Marcocci L, Amendola R, Cecconi F, Sabatini S, Mariottini P, Cervelli M (2017) Adaptive responses of heart and skeletal muscle to spermine oxidase overexpression: evaluation of a new transgenic mouse model. Free Radic Biol Med 103:216-225. https://doi.org/10.1016/j.freeradbiomed.2016.12.040
  77. Kim S, Kim D, Roh S, Hong I, Kim H, Ahn TS, Kang DH, Lee MS, Baek MJ, Kwak HJ, Kim CJ, Jeong D (2022) Expression of spermine oxidase is associated with colorectal carcinogenesis and prognosis of patients. Biomedicines 10:626. https://doi.org/10.3390/biomedicines10030626
  78. Fratini E, Cervelli M, Mariottini P, Kanamori Y, Amendola R, Agostinelli E (2019) Link between spermine oxidase and apoptosis antagonizing transcription factor: a new pathway in neuroblastoma. Int J Oncol 55:1149-1156. https://doi.org/10.3892/ijo.2019.4878
  79. Nauseef WM (1987) Posttranslational processing of a human myeloid lysosomal protein, myeloperoxidase. Blood 70:1143-1150 https://doi.org/10.1182/blood.V70.4.1143.1143
  80. Xie L, Qin WX, He XH, Shu HQ, Yao GF, Wan DF, Gu JR (2004) Differential gene expression in human hepatocellular carcinoma Hep3B cells induced by apoptosis-related gene BNIPL-2. World J Gastroenterol 10:1286-1291. https://doi.org/10.3748/wjg.v10.i9.1286
  81. Khan AA, Alsahli MA, Rahmani AH (2018) Myeloperoxidase as an active disease biomarker: recent biochemical and pathological perspectives. Med Sci (Basel) 6:33. https://doi.org/10.3390/medsci6020033