Ratlarda Etil Alkole Toksikasyonunun Neden Olduğu Inflamatuar Sitokinleri Yeşil Çay Azaltır

Abstract

Amaç: Yeşil çay (YÇ)’nin karaciğerdeki antioksidan ve antiinflamatuar etkinliğini gösteren sınırlı sayıda çalışmalar bulunmaktadır. Amacımız Etil alkol (EA) toksisitesine maruz kalan sıçanların karaciğer dokularındaki TNF-α ve Il-6 sitokinlerinin ekspresyonları ile oksidatif stres üzerindeki potansiyel tedavi mekanizmalarını ortaya koymaktır. Materyal/Metod: Çalışmamızda kullanılan 28 adet, rastgele seçilerek eşit sayıda dört gruba ayrıldılar. Group I: Control, Group II: YÇ grubu 7 gün boyunca içme suyu yerine YÇ verildi. Grup III: EA grubu, 7 gün süreyle günlük 5 g/kg dozunda subkutan uygulandı. Grup IV: EA+YÇ grubu olarak belirlendi. Deneysel işlemlerin sonunda oksidatif hasarı belirlemek için Malondialdehit (MDA), Toplam antioksidan (TAS) ve Toplam oksidan (TOS) durumları değerlendirildi. Karaciğerden alınan spesmenlerin ise inflamatuar sitokin yoğunluğuna bakıldı. Bulgular: Karaciğer fonksiyon testleri (AST ve ALT) EA uygulaması ile dikkat çekici oranda yükselmiş, EA+YÇ uygulaması ile değerler anlamlı olarak azalmıştı. Oksidatif stres belirteçlerinde ise (TOS ve MDA) benzer sonuçların doğduğu gözlendi. EA uygulaması ile TNF-α ve Il-6 sitokinlerinin (+) sinyalizasyonları EA+YÇ grubunda azalmıştı. Ayrıca EA grubunun karaciğer dokularında gözlenen konjesyon, vena sentraliste dejenerasyon, sinuzoidlerde dilatasyon, EA+YÇ grubunda yerini rejeneratif değişikliklere bıraktığı izlendi. Sonuç: EA toksisitesine bağlı olarak oksidatif stres ve inflamatuar sitokin salınımı artarken, YÇ’ın antiinflamatuar ve antioksidan özelliği sayesinde terapötik bir ajan olabileceği bulunmuştur.

Keywords

• Etil alkol
• Yeşil Çay
• Hepatotoksisite
• Inflamasyon
• Oksidatif stres

Green Tea Reduces TNF-Alpha and IL-6 Inflammatory Cytokines Induced by Ethyl Alcohol Toxication in Rats

Abstract

Objective: Studies investigating the antioxidant and anti-inflammatory effects of green tea (GT) on liver tissue are limited in number. This study aims to reveal the therapeutic mechanisms through which green tea modulates the inflammatory and oxidative stress responses caused by ethyl alcohol (EA) toxicity. Methods: The 28 Wistar albino rats used in our study were randomly selected and divided into four equal groups. Group I: Control, Group II: GT group, administered for 7 days instead of drinking water. Group III: EA group, administered subcutaneously at a daily dose of 5 g/kg for 7 days. Group IV: EA+GT group, 5 g/kg EA was administered daily for 7 days and the next day, the rats were given GT instead of drinking water for 7 days. Results: Increased AST, ALT, TOS, and MDA values with the EA application showed a significant decrease in the EA+GT group. Positive signals of TNF-α and IL-6 cytokines decreased in the EA+GT group. In addition, pathological findings such as degeneration and dilatation in tissues belonging to the EA group were replaced by regenerative changes in the EA+GT group. Conclusion: EA toxicity has been associated with increased oxidative stress levels and inflammatory cytokine release. In contrast, GT's anti-inflammatory and antioxidant properties suggest it may be a potential therapeutic agent against hepatotoxicity.

Keywords

• Ethyl alcohol
• green tea
• hepatotoxicity
• inflammation
• oxidative stress

References

1. Purohit V, Brenner DA. Mechanisms of alcohol-induced hepatic fibrosis: a summary of the Ron Thurman symposium. Hepatol. 2006;43(4);872–8. doi: 10.1002/hep.21107.
2. Singal AK, Anand BS. Recent trends in the epidemiology of alcoholic liver disease. Clin Liver Dis. 2013;2(2):53–56. doi: 10.1002/cld.168.
3. Wong T, Dang K, Ladhani S, Singal AK, Wong RJ. Prevalence of alcoholic fatty liver disease among adults in the United States, 2001–2016. JAMA. 2019;321(17):1723–1725. doi: 10.1001/jama.2019.2276. Mellinger JL. Epidemiology of alcohol use and alcoholic liver disease. Clin Liver Dis. 2019;13(5):136–139. doi: 10.1002/cld.806.
4. Cederbaum AI. Alcohol metabolism. Clin Liver Dis. 2012;16(4):667–685. doi: 10.1016/j.cld.2012.08.002.
5. Galicia Moreno M, Gutiérrez Reyes G. The role of oxidative stress in the development of alcoholic liver disease. Rev Gastroenterol Mex. 2014;79(2):135–144. doi: 10.1016/j.rgmxen.2014.06.007.
6. Cederbaum AI. Cytochrome P450 2E1- dependent oxidant stres and upregulation of anti-oxidant defense in liver cells. JGH. 2006;21(3):22-5. doi: 10.1111/j.1440-1746.2006.04595.x.
7. Albano E. Alcohol, oxidative stress and free radical damage. Proc Nutr Soc. 2006;65(3):278-290. doi: 10.1079/pns2006496.
8. Kawaratani H, Tsujimoto T, Douhara A, et al. The effect of inflammatory cytokines in alcoholic liver disease. Mediat Inflamm. 2013:2013:495156. doi: 10.1155/2013/495156.

9. Mittal M, Siddiqui MR, Tran K, Reddy SP, Malik AB. Reactive oxygen species in inflammation and tissue injury. Antioxid Redox Signal. 2014;20(7):1126-1167. doi: 10.1089/ars.2012.5149.
10. Hussain Y, Singh J, Raza W, et al. Purpurin ameliorates alcohol-induced hepatotoxicity by reducing ROS generation and promoting Nrf2 expression. Life Sci. 2022;309:120964. doi: 10.1016/j.lfs.2022.120964.
11. Frei B, Higdon JV. Antioxidant activity of tea polyphenols in vivo: evidence from animal studies. J Nutr. 2003;133(10):3275-84. doi: 10.1093/jn/133.10.3275S.
12. Mahmood B, Mokhtar M, Esfandiar S. The Impact of Green Tea (Camellia Sinensis) on the Amount of Gonadotropin Hormones (LH, FSH) in Immature Female Rats Poisoned with Cadmium Chloride. BPJ. 2015;8(1):261–8. doi: 10.13005/bpj/607.
13. Sharma P, Goyal PK. Anti-oxidative and anti-metalotoxic properties of gren tea catechin: a preliminary study. Am J Ethnomed. 2015;2(1):21–38. ISSN: 2348-9502.
14. Winiarska MA. The potential protective effect of green, black, red and white tea in fusions against adverse effect of cadmium and lead during chronic exposure A rat model study. RTP. 2015;73(2):521–9. doi: 10.1016/j.yrtph.2015.10.007.
15. Crespy V, Williamson G. A review of the health effects of green tea catechins in in vivo animal models. J Nutr. 2004;134(12):3431–40. doi: 10.1093/jn/134.12.3431S.
16. Jia J, Chen L, Liu Y, Luan H, Jia Y. Genetically predicted green tea intake and the risk of arterial embolism and thrombosis. Thromb Res. 2023;217:21-26. doi:10.1016/j.thromres.2023.04.010.
17. Chu KO, Chan KP, Yang YP, et al. Effects of EGCG content in green tea extract on pharmaco kinetics, oxidative status and expression of inflammatory and apoptotic genes in the rat ocular tissues. J Nutr Biochem. 2015;26(11):1357–1367. doi: 10.1016/j.jnutbio.2015.07.001.
18. Farkhondeh T, Pourbagher Shahri AM, Ashrafizadeh M, et al. Green tea catechins inhibit microglial activation which prevents the development of neurological disorders. Neural Regen Res. 2020;15:1792. doi: 10.4103/1673-5374.280300.
19. Wang Y, Tian L, Wang Y, et al. Protective effect of Que Zui tea hot-water and aqueous ethanol extract against acetaminophen-induced liver injury in mice via inhibition of oxidative stress, inflammation and apoptosis. Food Funct. 2021;12:2468–2480. doi: 10.1039/d0fo02894k.
20. Steiner JL, Lang CH. Dysregulation of skeletal muscle protein metabolism by alcohol. Am J Physiol Endocrinol Metab. 2015;308(9):E699–712. doi: 10.1152/ajpendo.00006.2015.
21. 22. Lang CH, Lynch CJ, Vary TC. Alcohol-induced IGF-I resistance is ameliorated in mice deficient for mitochondrial branched-chain aminotransferase. J Nutr. 2010;140(5):932–8. doi: 10.3945/jn.109.120501.
22. Mehana EE, Meki ARM, Fazili KM. Amelioratedeffects of greenteaextract on lead induced liver toxicity in rats. Exp Toxicol Pathol. 2012;64(4):291–5. doi: 10.1016/j.etp.2010.09.001.
23. Draper HH, Hadley M. Malondialdehyde determination as index of lipid Peroxidation. Methods Enzymol. 1990;186:421–431. doi: 10.1016/0076-6879(90)86135-i.
24. Erel O. A novel automated method to measure total antioxidant response against potent free radical reactions. Clin Biochem. 2004;37:112-119. doi: 10.1016/j.clinbiochem.2003.10.014.
25. Erel O. A new auto mated colorimetric method formeasuring total oxidant status. Clin Biochem. 2005;38:1103–11. doi: 10.1016/j.clinbiochem.2005.08.008.
26. Camargo Jr CA, Madden JF, Gao W, Selvan RS, Clavien PA. Interleukin-6 protects liver against warm ischemia/reperfusion injury and promotes hepatocyte proliferation in the rodent. Hepatol. 1997;26(6):1513–20. doi: 10.1002/hep.510260619.
27. Ayaz H, Aşır F, Korak T. Skimmianine Showed Neuroprotection against Cerebral Ischemia/Reperfusion Injury. Curr Issues Mol Biol. 2024;46(7):7373-7385. doi: 10.3390/cimb46070437.
28. Cederbaum AI. Alcohol metabolism. Clin Liver Dis. 2012;16:667–865. doi: 10.1016/j.cld.2012.08.002.
29. Liu SY, Tsai IT, Hsu YC. Alcohol-related liver disease: basic mechanisms and clinical perspectives. Int J Mol Sci. 2021;22(10):5170. doi: 10.3390/ijms22105170.
30. Xu L, Yu YF, Sang R, Li J, Ge B, Zhang X. Protective effects of taraxasterol against ethanol-induced liver injury by regulating CYP2E1/Nrf2/HO-1 and NF- κB signaling pathways in mice. Oxid Med Cell Longev. 2018:2018:8284107. doi: 10.1155/2018/8284107.
31. Mehta G, Macdonald S, Cronberg A, et al. Short-term abstinence from alcohol and changes in cardiovascular risk factors, liver function tests and cancer-related growth factors: A prospective observational study. BMJ Open. 2018;8(5):e020673. doi: 10.1136/bmjopen-2017-020673.
32. Suresh MV, Menon B, Indira M. Effects of exogenous vitamin C on ethanol toxicity in rats. Indian J Physiol Pharmacol. 2000;44(4):401-10.
33. Tomic ZB, Milijasevic A, Sabo L, et al. Vasovic Diclofenac and ketoprofen liver toxicity in rat. Eur J Drug Metab Pharm. 2008;33(4):253-260. doi: 10.1007/BF03190881.
34. Neuman MG. Cytokines central factors in alcoholic liver disease. Alcohol Res Health. 2003;27: 307-316.
35. Jurczuk M, Brzoska MM, Moniuszko-Jakoniuk J, Galazyn Sidorczuk M, Kulikowska Karpinska E. Antioxidant enzymes activity and lipid peroxidation in liver and kidney of rats exposed to cadmium and ethanol. Food Chem Toxicol. 2004;42(3):429-438. doi: 10.1016/j.fct.2003.10.005.
36. Yamamoto M, Yoshizaki K, Kishimoto T, Ito H. IL-6 is required for the development of Th1 cell-mediated murine colitis. J Immunol. 2000;164(9):4878-82. doi: 10.4049/jimmunol.164.9.4878.
37. Xing Z, Gauldie J, Cox G, et al. IL-6 is an antiinflammatory cytokine required for controlling local or systemic acute inflammatory responses. J Clin Invest. 1998;101:311-20. doi: 10.1172/JCI1368.
38. Peluso I, Serafini M. Antioxidants from black and Green tea: from dietary modulation of oxidative stress to pharmacological mechanisms. Br J Pharmacol. 2017;174(11):1195-08. doi: 10.1111/bph.13649.
39. Prasanth MI, Sivamaruthi BS, Chaiyasut C, Tencomnao T. A review of the role of green tea (Camellia sinensis) in antiphotoaging, stress resistance, neuroprotection, and autophagy. Nutrients. 2019;11(2):474. doi: 10.3390/nu11020474.
40. Lee LS, Kim SH, Kim YB, Kim YC. Quantitative analysis of major constituents in green tea with different plucking periods and their antioxidant activity. Molecules. 2014;19:9173–86. doi: 10.3390/molecules19079173.
41. Lambert JD, Elias RJ. The antioxidant and pro-oxidant activities of green tea polyphenols: A role in cancer prevention. Arch Biochem Biophys. 2010;501:65–72. doi: 10.1016/j.abb.2010.06.013.
42. Augustyniak A, Waszkiewicz E, Skrzydlewska E. Preventive action of gren tea from changes in the liver antioxidant abilities of different aged rats intoxicated with ethanol. Nutr. 2005;21(9):925-932. doi: 10.1016/j.nut.2005.01.006.
43. Ren JL, Yu QX, Liang WC, et al. Green tea extract attenuates LPS-induced retinal inflammation in rats. Sci Rep. 2018;8(1):429. doi: 10.1038/s41598-017-18888-5.