Hüseyin Avni EROĞLU, Mustafa MAKAV, Gülname FINDIK GÜVENDİ, Başak BÜYÜK, Yasemen ADALI

Ozon vs. Melatonin: Alkolik Karaciğer Hastalığında Terapötik Etkileri

Amaç: Alkolik karaciğer hastalığı (ALD) dünya çapında bir sağlık sorunudur. Ozon ve melatonin tıbbi tedavilerdeki antioksidan özellikleri için yaygın olarak kullanılan ajanlardır. Biz bu çalışmada ALD’de ozon ve melatonin kullanımını değerlendirmeyi amaçladık.Materyal ve Metod: Kırk sekiz sıçan kullanılmış ve etanol, melatonin ve ozon uygulanmıştır. Histopatolojik değerlendirme yapılmıştır ve kanda alanin aminotransferaz (ALT), aspartat aminotransferaz (AST), gama glutamil transferaz (GGT), total antioksidan kapasite (TAK), total oksidan kapasite (TOK) ve malondialdehit (MDA); karaciğer dokusunda TAK, TOK ve MDA parametreleri ölçülmüştür.Bulgular: Çalışılan gruplar arasında ALT, AST aktiviteleri ve TAK, TOK ve MDA düzeyleri açısından istatistiksel olarak anlamlı fark vardı. Alkol kaynaklı toksisite grubunda vasküler konjesyon, hepatosit hasarı, periportal inflamasyon ve mikrovesiküler steatoz tespit edildi.Sonuç: Histopatolojik bulgular ışığında melatonin ve ozon uygulamalarının alkole bağlı hepatotoksisite için faydalı olduğunu iddia edebiliriz. Bununla birlikte, ozon uygulaması melatoninden daha üstündür.Anahtar kelimeler: Alkole Bağlı Bozukluklar, Alkolik Karaciğer Hastalıkları, Melatonin, Ozon, Oksidatif Stres

Anahtar Kelimeler:

Alkole Bağlı Bozukluklar, Alkolik Karaciğer Hastalıkları, Melatonin, Ozon, Oksidatif stres

Ozone vs Melatonin: The Therapeutic Effects In Alcoholic Liver Disease

Background: Alcoholic liver disease (ALD) is a worldwide health problem.Ozone and melatonin are agents that are widely used for their antioxidant properties in medical therapies.In this study, we aimed to evaluate the use of ozone and melatoninin ALD.Materials and Methods: Forty-eight rats were used and ethanol, melatonin, and ozone were administrated. Histopathological evaluation was performed and activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma glutamyl transferase (GGT) total antioxidant status (TAS), total oxidant status (TOS), and malondialdehyde (MDA)were determined in the blood samples, while TAS, TOS, and MDA parameters were measured in the liver tissue samples.Results: There were statistically significant differences between the studied groups concerning ALT, AST activities and TAS, TOS, and MDA levels. Vascular congestion, hepatocyte damage, periportal inflammation, and microvesicular steatosis were detected inthe alcohol-induced toxicity group.Conclusions: In the light of histopathological findings, we can claim that melatonin and ozone administrations are beneficial for alcohol-induced hepatotoxicity. However, ozone application is superior to melatonin.

Keywords:

Alcohol-Induced Disorders, Alcoholic Liver Diseases, Melatonin, Ozone, Oxidative stress,

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1. Torruellas C, French SW, Medici V. Diagnosis of alcoholic liver disease. World J Gastroenterol. 2014 20(33): 11684-99. doi: 10.3748/wjg. v20.i33.11684.
2. European Association for the Study of the Liver. EASL clinical practical guidelines: management of alcoholic liver disease. J. Hepatol. 2012, 57: 399-420.
3. Ceni E, Mello T, Galli A. Pathogenesis of alcoholic liver disease: role of oxidative metabolism. World J Gastroenterol. 2014 20(47): 17756-72. doi: 10.3748/wjg. v20.i47.17756.
4. Gökhan Köker, Yasin Şahintürk, Ayhan Hilmi Çekin. Alkolik Karaciğer Hastalıkları. Güncel Gastroentereloji Dergisi. 2015, 19(2): 104-111
5. Crabb DW. Pathogenesis of alcoholic liver disease: Newer mechanisms of injury. Keio J Med 1999; 48: 184-188
6. Becker U, Deis A, Sørensen TI, Grønbaek M, Borch-Johnsen K, Müller CF, Schnohr P, Jensen G. Prediction of risk of liver disease by alcohol intake, sex, andage: a prospective population study. Hepatology. 1996; 23: 1025-1029.
7. León Fernández OS, Ajamieh HH, Berlanga J, Menéndez S, Viebahn‐ Hánsler R, Re L, et al. Ozone oxidative preconditioning is mediatedby A1 adenosine receptors in a rat model of liver ischemia/reperfusion. Transplant 2008, 21(1): 39-48. doi: 10.1111/j.1432-2277.2007.00568.x
8. Özlem Güzel, Esma Yildar, Dilek Olgun Erdikmen. Medikal Ozon ve Veteriner Cerrahide Kullanımı. J Fac Vet Med İstanbul Üniv. 2011, 37 (2): 177-184.
9. Tezcan AH, Ozturk O, Ustebay S, Adali Y, Yagmurdur H. The beneficial effects of ozone therapy in acetaminophen-induced hepatotoxicity in mice. Pharmacol Rep. 2018, 70(2): 340-345. doi: 10.1016/j.pharep.2017.11.003.
10. Ajamieh HH, Menéndez S, Merino N, Martínez-sánchez G, Re L, León OS. Ischemic and ozone oxidative preconditioning in the protection against hepatic ischemic-reperfusion injury. Ozone: Science & Engineering. 2003 25(3): doi.org/10.1080/01919510390481568.
11. Reiter RJ. Functional aspects of the pineal hormone melatonin in combating cell and tissue damage induced by free radicals. Eur J Endocrinol. 1996, 134:412-420.
12. Ianas 0, Olivescu ' R, Badescu I. Melatonin involvement in oxidative processes. Rom J Endocrinol. 1991; 29:117-123.
13. E. Sibel Namiduru, İclal Meram, Mehmet Tarakcioglu. Melatonin. The Medical Journal of Kocatepe. 2001, 2: 139- 146.
14. Committee for the Update of the Guide for the Care and Use of Laboratory Animals. Guide for the Care and Use of Laboratory Animals. 2011. doi: 10.17226/12910.
15. Schulz KF, Altman DG, Moher D. The consort statement: revised recommendations for improving the quality of reports of parallel group randomized trials (TurkishTranslation). Euras J Fam Med 2013, 2: 1-10.
16. Vidali M, Stewart SF, Albano E. Interplay between oxidative stress and immunity in the progression of alcohol-mediated liver injury. Trends Mol Med. 2008 Feb;14(2):63-71. doi: 10.1016/j.molmed.2007.12.005.
17. Lu SC, Martinez-Chantar ML, Mato JM. Methionine adenosyltransferase and S-adenosylmethionine in alcoholic liver disease. J Gastroenterol Hepatol. 2006;21 Suppl3:S61-4
18. Rambaldi A, Gluud C. S-adenosyl-L-methionine for alcoholic liver diseases. Cochrane Database Syst Rev. 2006(2):CD002235.
19. Lu B, Xu Y, Xu L, Cong X, Yin L, Li H, Peng J. Mechanism investigation of dioscin against CCl4-induced acute liver damage in mice. Environ Toxicol Pharmacol. 2012 Sep;34(2):127-135. doi: 10.1016/j.etap.2012.03.010.
20. Hu S, Yin S, Jiang X, Huang D, Shen G. Melatonin protects against alcoholic liver injury by attenuating oxidative stress, inflammatory response, and apoptosis. Eur J Pharmacol. 2009;616(1-3):287-92. doi: 10.1016/j.ejphar.2009.06.044.
21. Ogeturk M, Kus I, Kavakli A, Zararsiz I, Ilhan N, Sarsilmaz M. Effects of melatonin on carbon tetrachloride-induced changes in rat serum. J Physiol Biochem. 2004, 60(3):205-10.
22. Sigala F, Theocharis S, Sigalas K, Markantonis-Kyroudis S, Papalabros E, Triantafyllou A, Kostopanagiotou G, Andreadou I. Therapeutic value of melatonin in an experimental model of liver injury and regeneration. J Pineal Res. 2006, 40(3):270-9.
23. Ničković VP, Novaković T, Lazarević S, Šulović L, Živković Z, Živković J, Mladenović B, Stojanović NM, Petrović V, Sokolović DT. Pre- vs. post-treatment with melatonin in CCl(4)-induced liver damage: Oxidative stress inferred from biochemical and pathohistological studies. Life Sci. 2018, 4. pii:S0024-3205(18)30184-X. doi: 10.1016/j.lfs.2018.04.003.
24. Ohta Y, Kongo-Nishimura M, Matsura T, Yamada K, Kitagawa A, Kishikawa T. Melatonin prevents disruption of hepatic reactive oxygen species metabolism in rats treated with carbon tetrachloride. J Pineal Res. 2004;36(1):10-7.
25. Gul H, Uysal B, Cakir E, Yaman H, Macit E, Yildirim AO, Eyi YE, Kaldirim U, Oztas E, Akgul EO, Cayci T, Ozler M, Topal T, Oter S, Korkmaz A, Toygar M, Demirbag S. The protective effects of ozone therapy in a rat model of acetaminophen-induced liver injury. Environ Toxicol Pharmacol. 2012, 34(1):81-6. doi: 10.1016/j.etap.2012.02.006.
26. Gultekin FA, Bakkal BH, Guven B, Tasdoven I, Bektas S, Can M, Comert M. Effects of ozone oxidative preconditioning on radiation-induced organ damage in rats. J Radiat Res. 2013 Jan;54(1):36-44. doi: 10.1093/jrr/rrs073.
27. Mortezaee K, Majidpoor J, Daneshi E, Abouzaripour M, Abdi M. Post-treatment of melatonin with CCl(4) better reduces fibrogenic and oxidative changes in liver than melatonin co-treatment. J Cell Biochem. 2018 Feb;119(2):1716-1725. doi: 10.1002/jcb.26331.
28. Adali Y, Eroǧlu HA, Makav M, Guvendi GF. Efficacy of Ozone and Selenium Therapy for Alcoholic Liver Injury: An Experimental Model. In Vivo. 2019 May-Jun;33(3):763-769. doi: 10.21873/invivo.11537.
29. Mishra A, Paul S, Swarnakar S. Downregulation of matrix metalloproteinase-9 by melatonin during prevention of alcohol-induced liver injury in mice. Biochimie. 2011 May;93(5):854-66. doi: 10.1016/j.biochi.2011.02.007.
30. Noguchi T, Fong KL, Lai EK, Alexander SS, King MM, Olson L, et al. Specificity of a phenobarbital-induced cytochrome P-450 for metabolism of carbon tetrachloride to the trichloromethyl radical. Biochem Pharmacol. 1982;31(5):615-24.