Possible protective role of punicalagin on oxidative stress, inflammation and genotoxicity in ethanol-induced liver toxicity

Possible protective role of punicalagin on oxidative stress, inflammation and genotoxicity in ethanol-induced liver toxicity

Alcohol consumption is a tradition in most cultures but are increasingly being arised as possessing a potential for misuse. Punicalagin is a phenolic compound that is found in forms alpha and beta in pomegranates. In this study, the protective role of punicalagin on oxidative stress, inflammation and DNA damage caused by ethanol (EtOH) in liver tissue were examined. Wistar albino rats were divided into 4 groups as control, eth, punicalagin, EtOH EtOH + punicalagin. In EtOH groups, rats were treated with EtOH (4g/kg) for 21 days, in punicalagin groups, rats were treated with punicalagin (4 mg/kg) for 21 days. In the liver tissue, superoxide dismutase (SOD), catalase (CAT) activities and malondialdehyde (MDA) and glutathione (GSH) levels, in serum AST, ALT, LDH activities and TNF-α, IL-6 levels were measured. Genotoxicity was evaluated using comet assay. Based on these experimental results, while EtOH increased ALT, AST and LDH enzyme activies and induced inflammation and oxidative stress. Punicalagin reduced IL6, TNF-α, MDA levels, ALT, AST, LDH enzyme activities and increased SOD, CAT activities and GSH levels. EtOH significantly increased the percentage of damaged cells (type II, III and IV) and genetic damage index compared to the other groups (control, punicalagin and EtOH +punicalagin). Punicalagin was not genotoxic compared to the control. Furthermore, punicalagin reduced the genotoxic effect, induced by EtOH, with the sharp decrease in damaged cells (from 14.00±1.22 to 2.20±1.30) and genetic damage index (from 1.20±0.05 to 0.14±0.05). Punicalagin has antioxidant, antiinflammatory and protective role against to ethanol induced liver toxicity.

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  • [1] Gürsoy F. Master Thesis. The role of matrix metalloproteinases and the effect of antioxidants in ethanol-induced liver damage. Department of Biochemistry, Faculty of Medicine, Afyon Kocatepe University, Afyonkarahisar, Turkey, 2005.
  • [2] Wang X, Chang X, Zhan H, Zhang Q, Li C, Gao Q, Sun Y. Curcumin and Baicalin ameliorate ethanol‐induced liver oxidative damage via the Nrf2/HO‐1 pathway. J Food Biochem. 2020; 44: e13425.
  • [3] Adachi M, Higuchi H, Miura S, Azuma T, Inokuchi S, Saito H, Kato S, Ishii H. Bax interacts with voltage-dependent anion channel and mediates ethanol-induced apoptosis in rat hepatocytes. Am J Physiol. 2004; 287: 695–705.
  • [4] Yan LJ, Sohal RS. Mitochondrial adenine nucleotide translocase is modified oxidatively during aging. Proceedings of the National Academy of Sciences. 1998; 95: 896-901.
  • [5] Yan LJ. Positive oxidative stress in aging and aging-related disease tolerance. Redox Biology. 2014; 9: 165-169.
  • [6] Dokuyucu R, Karateke A, Gökce H, Kurt RK, Özcan O, Öztürk S. Antioxidant effect of erdosteine and lipoic acid in ovarian ischemia-reperfusion injury. Eur J Obstet Gynecol Reprod Biol. 2014; 183: 23-27.
  • [7] Yalın AE, Yalın S, Yıldız ŞM, Yüzbaşıoğlu S, Aksoy K. Eritrosit membran proteinlerine serbest radikallerin etkisi. Türk Biyokimya Dergisi. 2001; 26: 123-129.
  • [8] Blasiak J, Trzeciak A, Malecka-Panas E, Drzewoski J, Wojewodzka M. In vitro genotoxicity of ethanol and acetaldehyde in human lymphocytes and the gastrointestinal tract mucosa cells. Toxicol In Vitro. 2000; 14: 287-295.
  • [9] Özden S. PhD Thesis. Investigation of oxidative stress potentials and effects of some pesticides on antioxidant systems in rats. Department of Pharmaceutical Toxicology, Faculty of Pharmacy, İstanbul University, İstanbul, Turkey, 2006.
  • [10] Jayaraman J, Namasivayam N. Naringenin modulates circulatory lipid peroxidation, anti‐oxidant status and hepatic alcohol metabolizing enzymes in rats with ethanol induced liver injury. Fundam Clin Pharmacol. 2011;25: 682-689.
  • [11] Mercan U. Toksikolojide serbest radikallerin önemi. Van Vet J. 2004;15(1-2):91-96.
  • [12] Serafini M, Rio D. Understanding the association between dietray antioxidants, redox status and disease: Is the Total Antioxidant Capacity the Right Tool. Redox Report. 2004; 9(3): 145-152.
  • [13] Halliwell B, Gutteridge MC. Role of free radicals and catalytic metal ions in human disease: An overview. Methods Enzymol. 1990; 186: 1-85.
  • [14] Ikeda Y, Long DM. The molecular basis of brain injury and brain edema: The role of oxygen free radicals. Neurosurgery. 1990; 27(1): 1-11.
  • [15] Janssen YMW, Houten BV, Borm PJA, Mossmon BT. Biology of disease, cell and tissue responses to oxidative damage. Lab Invest. 1993; 69(3): 261-274.
  • [16] Aykaç G, Uysal M, Süha-Yalçin A, Koçak-Toker N, Sivas A, Öz H. The effect of chronic ethanol ingestion on hepatic lipid peroxide, glutathione, glutathione peroxidase and glutathione transferase in rats. Toxicology. 1985; 36(1): 71-76.
  • [17] Sonde V, D’souza A, Tarapore R, Pereira L, Khare MP, Sinkar P, Krishnan S, Rao CV. Simultaneous administration of diethylphthalate and ethyl alcohol and its toxicity in male Sprague-Dawley rats. Toxicology. 2000; 47(1): 23-31.
  • [18] Kolankaya D, Selmanoğlu G, Sorkun K, Salih B. Protective effects of Turkish propolis on alcohol-induced serum lipid changes and liver injury in male rats. Food Chem. 2002; 78(2): 213-217.
  • [19] Yurt B. PhD Thesis. Determination of liver protective and antioxidant effects of apricot and apricot kernels in rats with oxidative stress with ethyl alcohol. Van Yüzüncü Yıl University, Van, Turkey, 2010.
  • [20] Ganapathi SC, Holla R, Shankara S, Mundugaru R, Sunilkumar KN, Rajagopal R, AlAnsari A. Protective effect of ethanolic extract of Actinoscirpus grossus tubers against ethanol induced liver toxicity in albino rats. J King Saud Univ Sci. 2021; 33: 101253.
  • [21] Akkuş İ. Serbest Radikaller ve Fizyopatolojik Etkileri, Konya, Turkey, 1995.
  • [22] Niki E. Antioxidant in relation to lipid peroxidation. Chem Phys Lipids. 1987; 44(2-4): 227-253.
  • [23] Duthie GG, Wahle KWJ, James WPT. Oxidants, antioxidants and cardiovascular disease. Nutr Res Rev. 1989; 2(1): 51- 62.
  • [24] Clemens MC, Waller HD. Lipid peroxidation in erythrocytes. Chem Phys Lipids. 1987; 45(2-4): 251-268.
  • [25] Van Zutphen LFM, Baumans V, Beynen AC. Laboratuvar Hayvanları Biliminin Temel İlkeleri, Malatya, Turkey, 2003.
  • [26] Yurt B. PhD Thesis. Determination of liver protective and antioxidant effects of apricot and apricot kernels in rats with oxidative stress with ethyl alcohol. Van Yüzüncü Yıl University, Van, Turkey, 2010.
  • [27] Doğan A. Master Thesis. Determination of liver protective and antioxidant role of grape (vitis vinifera l.) seed in rats with experimental oxidative stress with ethyl alcohol. Van Yüzüncü Yıl University, Van, Turkey, 2010.
  • [28] Souli A, Sebai H, Chehimi L, Rtibi K, Tounsi H, Boubaker S, Amri M. Hepatoprotective effect of carob against acute ethanol-induced oxidative stress in rat. Toxicol Ind Health. 2015; 31: 802-810.
  • [29] Pramyothin P, Samosorn P, Poungshompoo S, Chaichantipyuth C. The protective effects of Phyllanthus emblica Linn. extract on ethanol induced rat hepatic injury. J Ethnopharmacol. 2006; 107:361-364.
  • [30] Sushil JK, Mcvie R, Duett J, Herbst JJ. Erythrocyte membrane lipid peroxidation and glycosylated hemoglobin in diabetes. Diabetes. 1989; 38(12): 1539-1543.
  • [31] Porter NA. Chemistry of lipid peroxidation. Methods Enzymol. 1984; 105: 273-283.
  • [32] Tan H, He Q, Li R, Lei F, Lei X. Trillin reduces liver chronic inflammation and fibrosis in carbon tetrachloride (CCl4) induced liver injury in mice. Immunol Invest. 2016; 45: 371-382.
  • [33] Shah TA, Parikh M, Patel KV, Patel KG, Joshi CG, Gandhi TR. Evaluation of the effect of Punica granatum juice and punicalagin on NFκB modulation in inflammatory bowel disease. Mol Cell Biochem. 2016; 419: 65-74.
  • [34] Quertemont E. Genetic polymorphism in ethanol metabolism: acetaldehyde contribution to alcohol abuse and alcoholism. Mol Psychiatry. 2004; 9: 570-581.
  • [35] Navasumrit P, Ward TH, Dodd NJ, O'Connor PJ. Ethanol-induced free radicals and hepatic DNA strand breaks are prevented in vivo by antioxidants: effects of acute and chronic ethanol exposure. Carcinogenesis. 2000; 21: 93-99.
  • [36] Sedlak J, Lindsay RH. Estimation of Total Protein-Bound, and Nonprotein Sulfhydryl Groups in Tissue with Ellman’s Reagent. Anal Biochem. 1968; 25(1): 1192-1205.
  • [37] Aebi H. Catalase In Vitro. Methods Enzymol. 1984; 105: 121-126.
  • [38] Sun Y, Oberley LW, Li YA. Simple Method for Clinical Assay of Superoxide Dismutase. Clin Chem. 1988; 34(3): 497- 500.
  • [39] Waterborg JH, The Lowry method for protein quantitation. In The protein protocols handbook. Humana Press, Totowa, NJ. USA 2009
  • [40] Singh NP, McCoy MT, Tice RR, Schneider EL. A simple technique for quantitation of low levels of DNA damage in individual cells. Exp. Cell Res. 1988; 175: 184–191.
Journal of research in pharmacy (online)-Cover
  • Yayın Aralığı: Yılda 6 Sayı
  • Yayıncı: Marmara Üniversitesi
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