Vücut sıvılarında Antemortem - Postmortem Etil Alkol Düzeyinin Belirlenmesinde Kullanılan Biyobelirteçler

Yıl 2016, Cilt: 30 Sayı: 2, 153 - 161, 31.08.2016

Mahmut Aşırdizer Yasin Etli Orhan Gümüş Erhan Kartal Yavuz Hekimoğlu

https://izlik.org/JA39YF79EE

Öz

Etil alkol kullanımı pek çok açıdan adli tıp pratiği ile çakışmaktadır. Bu durum etil alkol kullanımının ve postmortem üretiminin tespit edilmesini adli tıp açısından son derece önemli kılmaktadır. Buna karşın antemortem-postmortem alkol düzeylerinin belirlenmesinde klasik yöntemlerin pek çok durumda yetersiz kaldığı görülmektedir. Bu durum etil alkol kullanımının tespiti için ek yöntemlere ihtiyaç duyulmasına sebep olmaktadır. Gama Glutamil Transferaz, Ortalama Eritrosit Hacmi ve Karbonhidrat Takısı Eksik Transferrin gibi bazı yöntemlerin belli dezavantajlarının olması da kullanım alanlarını ve yararlarını sınırlamaktadır. Son yıllarda etanol kullanımının göstergesi olarak tanımlanan etil glukronid, etil sülfat, fosfatidiletanol, 5-hidroksitriptofol / 5-hidroksiindol asetik asit oranı ve yağ asidi etil esterleri gibi biyobelirteçlerin yararlılıkları pek çok çalışma ile kanıtlanmıştır. Bu derlemede, antemortem - postmortem etil alkol ayrımı konusunda bu tür yeni yöntemlerin kullanımının yaygınlaştırılmasının öneminin vurgulanması amaçlanmıştır.

Anahtar Kelimeler

Etil alkol , postmortem alkol üretimi , etil glukronid , etil sülfat , fosfatidiletanol , yağ asidi etil esterleri , 5-Hidroksitriptofol/5-Hidroksiindol asetik asit oranı

Biomarkers Used to Determine Antemortem and Postmortem Ethyl Alcohol Level in Body Fluids

https://izlik.org/JA39YF79EE

Öz

Consumption of ethyl alcohol has intersected with forensic science practice in many situations. This situation makes it highly important for forensic medicine to determine consumption and postmortem production of ethyl alcohol. For all that, classical methods can be insufficient to determine the antemortem and postmortem ethanol level in many situations. This causes a need for additional methods for the detection of ethyl alcohol. The presence of certain disadvantages of some methods such as Gama Glutamyl Transferase, Main Corpuscular Volume and Carbonhydrate Deficient Transferrin, it limits their utility and their usage areas. The usefulness of biomarkers such as ethyl glucuronide, ethyl sulfate, phosphatidylethanol, 5-Hydroxytryptophol/5-hydroxyindoleacetic acid ratio and fatty acid ethyl esters, which were determined as indicator of ethanol use in the last years has been proven in many studies. In the present review article, it was aimed that to emphasizing the importance of dissemination of using the similar new methods about identification of antemortem - postmortem ethanol.

Anahtar Kelimeler

Ethyl alcohol , postmortem alcohol production , ethyl glucuronide , ethyl sulfate , phosphatidylethanol , fatty acid ethyl esters , 5-Hydroxytryptophol / 5-Hydroxyindoleacetic acid ratio

Kaynakça

• Saukko P, Knight B. Forensic Aspects of Alcohol In: Saukko P, Knight B, eds. Knight’s Forensic Pathology 3rd Edition. London: Hodder Arnold,2004:552-9.
• Wagner K. Über die Veränderlichkeit des Alkoholge- haltes von Leichenblut und nichtsteril aufbewahrten Blut- proben. Deuts Z Ges Gerich Med 1936;26:276-92.
• Ziavrou K, Boumba VA, Vougiouklakis TG. Insights into the origin of postmortem ethanol. Int J Toxicol 2005;24 2 :69-77.
• Singer PP, Jones GR, Lewis R, Johnson R. Loss of etha- nol from vitreous humor in drowning death. J Anal Toxicol ;31 8 :522-5.
• Corry JE. A review: Possible sources of ethanol ante- and post-mortem: its relationship to the biochemistry and mi- crobiology of decomposition. J Appl Bacteriol 1978;44 1 :1-56.
• Caplan YH, Levine B. Vitreous humor in the evaluation of postmortem blood ethanol concentrations. J Anal Toxicol ;14 5 :305-7.
• Johnson RD, Lewis RJ, Canfield DV, Blank CL. Accurate assignment of ethanol origin in postmortem urine: liquid chromatographic-mass spectrometric determination of serotonin metabolites. J Chromatogr B Analyt Technol Biomed Life Sci 2004;805 2 :223-34.
• Wurst FM, Kempter C, Metzger J, Seidl S, Alt A. Ethyl glucuronide: A marker of recent alcohol consumption with clinical and forensic implications. Alcohol 2000;20 2 :111-6.
• Refaai MA, Nguyen PN, Steffensen TS, Evans RJ, Cluette- Brown JE, Laposata M. Liver and adipose tissue fatty acid ethyl esters obtained at autopsy are postmortem markers for premortem ethanol intake. Clin Chem 2002;48 1 :77-83.
• Best CA, Laposata M. Fatty acid ethyl esters: Toxic non- oxidative metabolites of ethanol and markers of ethanol intake. Front Biosci 2003;8:e202-17.
• Emrich J, Sprung R, Sammler J, Remberg G. Identifi- cation of fatty acid methyl esters FAMEs in postmortem tissue. A new marker of alcohol abuse? Forensic Sci Int ;85 1 :41-9.
• Ramchandani VA, Bosron WF, Li TK. Research advances in ethanol metabolism. Pathologie Biologie 2001;49 9 :676-82.
• Hansson P, Varga A, Krantz P, Alling C. Phosphatidyl- ethanol in post-mortem blood as a marker of previous heavy drinking. Int J Legal Med 2001;115 3 :158-61.
• Foti RS, Fisher MB. Assessment of UDP-glucuronos- yltransferase catalyzed formation of ethyl glucuronide in human liver microsomes and recombinant UGTs. Forensic Sci Int 2005;153 2-3 :109-16.
• Wurst FM, Dresen S, Allen JP, Wiesbeck G, Graf M, Weinmann W. Ethyl sulphate: a direct ethanol metabo- lite reflecting recent alcohol consumption. Addiction ;101 2 :204-11.
• Helander A, Beck O. Ethyl sulfate: A metabolite of etha- nol in humans and a potential biomarker of acute alcohol intake. J Anal Toxicol 2005;29 5 :270-4.
• Canfield DV, Kupiec T, Huffine E. Postmortem alco- hol production in fatal aircraft accidents. J Forensic Sci ;38 4 :914-7.
• de Lima IV, Midio AF. Origin of blood ethanol in decom- posed bodies. Forensic Sci Int 1999;106 3 :157-62.
• Grellner W, Iffland R. Assessment of postmortem blood alcohol concentrations by ethanol levels measured in fluids from putrefactive blisters. Forensic Sci Int 1997;90 1-2 :57-63.
• Asirdizer M. Forensic medical aspects of toxicological analysis results. 1. Forensic Toxicology Days, 14-16 April 2011, Istanbul. Available at: https://www.researchgate.net/ publication/279038395_Toksikolojik_Analiz_Sonularnn_ Adli_Tbbi_Yn cited: 23 June 2015 .
• Hİiseth G, Bernard JP, Stephanson N, Normann PT, Christophersen AS, Mİrland J, Helander A. Comparison between the urinary alcohol markers EtG, EtS, and GTOL/5- HIAA in a controlled drinking experiment. Alcohol Alcohol ;43 2 :187-91.
• Beck O, Helander A. 5-hydroxytryptophol as a marker for recent alcohol intake. Addiction 2003; 98 Suppl 2 :63-72.
• Svensson S, Some M, Lundsjö A, Helander A, Cronholm T, Höög JO. Activities of human alcohol dehydrogenases in the metabolic pathways of ethanol and serotonin. Eur J Biochem 1999;262 2 :324-9.
• Alling C, Gustavsson L, Månsson JE, Benthin G, Anggård E. Phosphatidylethanol formation in rat organs after etha- nol treatment. Biochim Biophys Acta 1984;793 1 :119-22.
• Hansson P, Caron M, Johnson G, Gustavsson L, Alling C. Blood phosphatidylethanol as a marker of alcohol abuse: levels in alcoholic males during withdrawal. Alcohol Clin Exp Res 1997;21 1 :108-10.
• Doyle KM, Cluette-Brown JE, Dube DM, Bernhardt TG, Morse CR, Laposata M. Fatty acid ethyl esters in the blood as markers for ethanol intake. JAMA 1996;276 14 :1152-6.
• Tümer AR, Keten A, Karacaoğlu E, BalsevenOdabaşı A, Akçan R, Evaluation of ethyl glucuronide, a minor me- tabolite of ethyl alcohol, accompanied by related cases. Hacettepe Tıp Derg 2011;42 3 :141-5.
• Karanfil R, Keten A, Zeren C, Rifaioğlu E N, Göktaş MT. Comparison of hair and nail ethyl glucuronide concentra- tions. Dicle Tıp Derg 2014;41 4 :635-9.
• Al-Asmari AI, Anderson RA, Appelblad P. Direct deter- mination of ethyl glucuronide and ethyl sulfate in postmor- tem urine specimens using hydrophilic interaction liquid chromatography-electrospray ionization-tandem mass spectrometry. J Anal Toxicol 2010;34 5 :261-72.
• Arndt T, Gierten B, Güssregen B, Werle A, Grüner J. False-positive ethyl glucuronide immunoassay screening associated with chloral hydrate medication as confirmed by LC-MS/MS and self-medication. Forensic Sci Int 2009;184 1-3 :e27-9.
• Beyer J, Vo TN, Gerostamoulos D, Drummer OH. Validated method for the determination of ethylglucuronide and ethylsulfate in human urine. Anal Bioanal Chem 2011;400 1 :189-96.
• Caslavska J, Jung B, Thormann W. Confirmation analysis of ethyl glucuronide and ethyl sulfate in human serum and urine by CZE-ESI-MS n after intake of alcoholic beverages. Electrophoresis 2011;32 13 :1760-4.
• Dahl H, Voltaire Carlsson A, Hillgren K, Helander A. Urinary ethyl glucuronide and ethyl sulfate testing for de- tection of recent drinking in an outpatient treatment pro- gram for alcohol and drug dependence. Alcohol Alcohol ;46 3 :278-82.
• Dahl H, Hammarberg A, Franck J, Helander A. Urinary ethyl glucuronide and ethyl sulfate testing for recent drink- ing in alcohol-dependent outpatients treated with acam- prosate or placebo. Alcohol Alcohol 2011;46 5 :553-7.
• Favretto D, Nalesso A, Frison G, Viel G, Traldi P, Ferrara SD. No-discharge atmospheric pressure chemical ioniza- tion mass spectrometry of ethyl glucuronide and ethyl sul- fate. J Mass Spectrom 2010;45 1 :121-4.
• Favretto D, Nalesso A, Frison G, Viel G, Traldi P, Ferrara SD. A novel and an effective analytical approach for the LC- MS determination of ethyl glucuronide and ethyl sulfate in urine. Int J Legal Med 2010;124 2 :161-4.
• Schmitt G, Aderjan R, Keller T, Wu M. Ethyl glucuronide: an unusual ethanol metabolite in humans. Synthesis, ana- lytical data, and determination in serum and urine. J Anal Toxicol 1995;19 2 :91-4.
• Helander A, Kenan N, Beck O. Comparison of analytical approaches for liquid chromatography/mass spectrometry determination of the alcohol biomarker ethyl glucuronide in urine. Rapid Commun Mass Spectrom 2010;24 12 :1737-43.
• Musshoff F, Albermann E, Madea B. Ethyl glucuronide and ethyl sulfate in urine after consumption of various beverages and foods--misleading results? Int J Legal Med ;124 6 :623-30.
• Stewart SH, Koch DG, Burgess DM, Willner IR, Reuben A. Sensitivity and specificity of urinary ethyl glucuronide and ethyl sulfate in liver disease patients. Alcohol ClinExp Res 2013;37 1 :150-5.
• You Y, Uboh CE, Soma LR, Guan F, Li X, Rudy JA, Chen J. Biomarkers of alcohol abuse in racehorses by liquid chro- matography/tandem mass spectrometry. Rapid Commun Mass Spectrom 2007;21 23 :3785-94.
• Hİiseth G, Bernard JP, Karinen R, Johnsen L, Helander A, Christophersen AS, Mİrland J. A pharmacokinetic study of ethyl glucuronide in blood and urine: applications to fo- rensic toxicology. Forensic Sci Int 2007;172 2-3 :119-24.
• Hİiseth G, Karinen R, Christophersen AS, Olsen L, Nor- mann PT, Mİrland J. A study of ethyl glucuronide in post- mortem blood as a marker of ante-mortem ingestion of alcohol. Forensic Sci Int 2007;165 1 :41-5.
• Keten A, Tumer AR, Balseven-Odabasi A. Measurement of ethyl glucuronide in vitreous humor with liquid chroma- tography-mass spectrometry. Forensic Sci Int 2009;193 1- :101-5.
• Vestermark A, Bostrom H. Studies on ester sulfates. V. On the enzymatic formation of ester sulfates of primary aliphatic alcohols. Exp Cell Res 1959;18 1 :174-7.
• Schneider H, Glatt H. Sulpho-conjugation of ethanol in humans in vivo and by individual sulphotransferase forms in vitro. Biochem J 2004;383 Pt.3 :543-9.