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Resveratrolün Hep3B Hücrelerinde Oluşturulan Parasetamol Toksisitesi Üzerindeki Etkilerinin Araştırılması

Yıl 2023, Cilt: 6 Sayı: 3, 288 - 301, 20.12.2023
https://doi.org/10.38001/ijlsb.1357213

Öz

Amaç: Mevcut çalışmada, asetamonifen ve muhtemel koruyucu etkisinin olabileceğini düşündüğümüz resveratrol’ün uygulandığı Hep3B insan hepatoma hücrelerinde oluşturulmuş asetaminofen kaynaklı hepatotoksisitenin incelenmesi amaçlanmıştır. Bu çalışmada özellikle bazı proinflamatuvar parametrelerin rolü ve asetaminofen-aracılı sitotoksisitenin muhtemel sebeplerinden biri olan oksidatif stres araştırılmıştır. Materyal ve Metot: Bu çalışma için Hep3B insan hepatoma hücre hattı kullanılmıştır. İn vitro çalışmalar (GSH, SOD, KAT, AST, ALT, TNF-alfa, IL-6 ve canlılık analiz testi), Biyokimyasal analizatör, ELISA, Real-Time PCR ve MTT gibi farklı metotlar kullanılarak gerçekleştirilmiştir. Asetaminofen ve resveratrol, hücrelere farklı doz ve zamanlarda uygulanmıştır. Bulgular: Hep3B hücrelerinde yalnızca asetaminofen uygulanan gruplarda SOD, KAT ve GSH seviyelerinde azalma tespit edilirken, asetaminofen ve resveratrol’ün beraber uygulandığı gruplarda bu enzimlere ait seviyeleri yükselmiştir. Diğer yandan, asetaminofen ve beraberinde yapılan resveratrol uygulamaları (özellikle 160 µM resveratrol dozu) TNF-alfa ve IL-6 seviyesinde ciddi bir artışa sebep olmuştur. Sonuç: Mevcut çalışmada, asetaminofen’in karaciğer toksisitesine sebep olduğunu ve ilginç bir şekilde resveratrol uygulamaları yukarıda belirtilen parametrelerin seviyelerini ciddi derecede etkilediği gösterilmiştir. Yalnızca asetaminofen uygulaması pro- inflamatuvar sitokin seviyelerinde ve anti-oksidant enzim seviyelerinde anormal artış ve/veya azalışlara sebep olmuştur. Buna ilaveten asetaminofen ile beraber yapılan yüksek doz resveratrol uygulaması inflamasyon ve oksidatif stres oluşumuna öncülük etmiştir. Bu sonuçlar, resveratrol’ün hepatik hasarın önlenmesi ve tedavisinde oldukça etkili bir ajan olabileceğini göstermektedir.

Kaynakça

  • Yapar, K., Kart, A., Karapehlivan, M., Atakisi, O., Tunca, R., Erginsoy, S., Citil, M. Hepatoprotective effect of L-carnitine against acute acetaminophen toxicity in mice, Exp Toxicol Pathol, 2007, 59: 121-8.
  • James, L.P., Mayeux, P.R., Hinson, J.A. Acetaminophen-induced hepatotoxicity. Drug metabolism and disposition: The biological fate of chemicals, 2003, 31: 1499- 1506.
  • Boobis, A.R., Seddon, C.E., Nasseri-Sina, P., Davies, D.S. Evidence for a direct role of intracellular calcium in paracetamol toxicity. Biochem Pharmacol, 1990, 39: 1277-1281.
  • Donnelly, P.J., Walker, R.M., Racz, W.J. Inhibition of mitochondrial respiration in vivo is an early event in acetaminophen-induced hepatotoxicity. Arch Toxicol, 1994, 68: 110-118.
  • Russmann, S., Ublick, A.G., Grattagliano, I. “Current consepts of mechanizms in drug-induced hepatotoxicity,” Curr Med Chem, 2009, 16, 2041–3053.
  • Castel, J.V., Jose, M., Ponsoda, X., Bort, R. “In vitro investigation of the molecular mechanisms of hepatotoxicity,” Invitro Meth Pharma Res, 1996, 13, 376-389.
  • BedÊ, T.P., Jesuz, V.A., Souza, V.R., Elias, M.B., Oliveira, F.L., Dias, J.F., Teodoro, A.J., Azeredo, V.B. Effects of Grape Juice, Red Wine and Resveratrol on Liver Parameters of Rat Submitted High-fat Diet. An. Acad. Bras. Cienc. 2020, 92.
  • Wine and Resveratrol on Liver Parameters of Rat Submitted High-fat Diet. An. Acad. Bras. Cienc. 2020, 92, e20191230. Fremont, L. Biological Effects of Resveratrol. Life Sciences, 1999, 66: 663-673.
  • Marques, F.Z., Markus, M.A, Morris, B.J. Resveratrol: Cellular actions of a potent natural chemical that confers a diversity of health benefits. Int. J. Biochem. Cell Biol. 2009, 41, 2125-2128.
  • Karabulut, A.B. Resveratrol ve Etkileri. Türkiye klinikleri J Med Sci, 2008, 28: 166-169.
  • Baur, J.A,. and Sinclair, D.A. Therapeutic potential of resveratrol: the in vivo evidence. Nat Rev Drug Discov, 2006, 5: 493–506.
  • Csiszar, A., Smith, K., Labinskyy, N. Resveratrol attenuates TNF- induced activation of coronary arterial endothelial cells: role of NF-kB inhibition. Am J Physiol Heart Circ Physiol. 2006, 291:1694-1699.
  • Baur, J.A., Singh, G., Srivastava, R.K., Chemoprevention by Resveratrol: Molecular Mechanisms and Therapeutic Potential. Front. Biosci. 2007, 12, 4839-4854.
  • Shakibaei, M., Harikumar, K.B., Aggarwal, B.B. Resveratrol Addiction: To Die or not to Die. Mol.Nutr.Food Res. 2009, 53,115-128.
  • Bernal, W., Wendon, J., Rela, M., Heaton, N., Williams, R. Use and outcome of liver transplantation in acetaminophen-induced acute liver failure. Hepatology, 1998, 27: 1050-1055.
  • Spooner, J.B., Harvey, J.G. The history and usage of paracetamol. J Int Med Res, 1976, 4: 1-6.
  • Newson, R.B., Shaheen, S.O., Chinn, S., Burney, P.G. Paracetamol sales and atopic disease in children and adults: an ecological analysis. Eur Respir J, 2000, 16: 817- 823.
  • Larson, A.M. Acetaminophen hepatotoxicity. Clin Liver Dis, 2007, 11: 525-548.
  • Swierkosz, T.A., Jordan, L., McBride, M., McGough, K., Devlin, J., Botting, RM. Actions of paracetamol on cyclooxygenases in tissue and cell homogenates of mouse and rabbit. Med Sci Monit, 2002, 8: 496-503.
  • Drotman, R.B., Lawhorn, G.T. Serum enzymes as indicators of chemically induced liver damage. Drug Chem Toxicol, 1978, 1: 163-171.
  • Janbaz, K.H., Saeed, S.A., Gilani, A.H. Protective effect of rutin on paracetamol- and CCl4-induced hepatotoxicity in rodents. Fitoterapia, 2002, 73: 557-563.
  • Ali, B.H., Bashir, A.K., Rasheed, R.A. Effect of the traditional medicinal plants Rhazya stricta Balanitis aegyptiaca and Haplophlyum tuberculatum on paracetamol-induced hepatotoxicity in mice. Phytotherapy Res, 2001, 15: 598-603.
  • Rabinovitz, M., Van, D.H. Hepatotoxicity of nonsteroidal anti-inflammatory drugs. Am J gastroenterol, 1992, 87: 1696-1704.
  • Upadhyay, G., Singh, A.K, Kumar, A., Prakash, O., Singh, M.H. Resveratrol Modulates Pyrogallol-induced Changes in Hepatic Toxicity Markers, Xenobiotic Metabolizing Enzymes and Oxidative Stress. Eur. J. Pharmacol. 2008, 596, 146-152.
  • Anundi, I., Lahteenmaki, T., Rundgren, M., Moldeus, P., Lindros, KO. Zonation of acetaminophen metabolism and cytochrome P450 2E1-mediated toxicity studied in isolated periportal and perivenous hepatocytes. Biochem Pharmacol, 1993, 45: 1251-1259.
  • Atkuri, K.R., Mantovani, J.J., Herzenberg, L.A. N-Acetylcysteine a safe antidote for cysteine/glutathione deficiency. Curr Opin Pharmacol, 2007, 7: 355-359.
  • Manda, K. Role of β-carotene against acetaminophen-induced hepatotoxicity in mice. Nutrition Res, 2003, 23: 1097-1103.
  • Yapar, K., Kart, A., Karapehlivan, M., Atakisi, O., Tunca, R., Erginsoy, S., Citil, M. Hepatoprotective effect of L-carnitine against acute acetaminophen toxicity in mice. Exp Toxicol Pathol, 2007, 59: 121-128.
  • Topic, B., Tani, E., Tsiakitzis, K., Kourounakis, P.N., Dere, E, Hasenohrl R.U, Hacker R, Mattern, C.M., Huston, J.P. Enhanced maze performance and reduced oxidative stress by combined extracts of zingiber officinale and ginkgo biloba in the aged rat. Neurobiol aging, 2002, 23: 135-143.
  • Brand, M.D., Affourtit, C., Esteves, T.C., Green, K., Lambert, A.J., Miwa, S., Pakay, J.L., Parker, N. Mitochondrial superoxide: production, biological effects, and activation of uncoupling proteins. Free rad biol med, 2004, 37: 755-767.
  • Gao, H., Zhou, Y.W. Anti-lipid peroxidation and protection of liver mitochondria against injuries by picroside II. World J Gastroenterol, 2005, 11: 3671-3674.
  • Olaleye, M.T., Rocha, B.T. Acetaminophen-induced liver damage in mice: effects of some medicinal plants on the oxidative defense system. Exp toxicol pathol, 2008, 59: 319-327.
  • Xu, H., Lin, L., Yuan, W.J. Antiarrhythmic effect of endothelin-A receptor antagonist on acute ischemic arrhythmia in isolated rat heart. Acta Pharmacol Sin, 2003, 24: 37-44.
  • Ozdemir, R., Parlakpinar, H., Polat, A., Colak, C., Ermis, N., Acet, A. Selective endothelin a (ETA) receptor antagonist (BQ-123) reduces both myocardial infarct size and oxidant injury. Toxicology, 2006, 219: 142-149.
  • Chularojmontri, L., Wattanapitayakul, S.K., Herunsalee, A., Charuchongkolwongse, S., Niumsakul, S., Srichairat, S. Antioxidative and cardioprotective effects of Phyllanthus urinaria L. on doxorubicin-induced cardiotoxicity. Biol Pharm Bull, 2005, 28: 1165-1171.
  • Awodele, O., Yemitan, O., Ise, P.U., Ikumawoyi, V.O. Modulatory potentials of aqueous leaf and unripe fruit extracts of Carica papaya Linn. (Caricaceae) against carbontetrachloride and acetaminophen-induced hepatotoxicity in rats. J Intercult Ethnopharmacol. 2016, 5: 27-35.
  • Uysal, H.B., Dağlı, B., Yılmaz, M., Kahyaoğlu, F., Gökçimen, A., Ömürlü, İ.K., Demirci, B. Biochemical and histological effects of thiamine pyrophosphate against acetaminophen-ınduced hepatotoxicity. Basic Clin Pharmacol Toxicol. 2016, 118: 70-6.
  • Malhi, H., Gores, G.J., Lemasters, J.J. Apoptosis and necrosis in the liver: a tale of two deaths? Hepatology, 2006, 43: 31-44.
  • Akerman, P,, Cote, P., Yang, SQ., McClain, C., Nelson, S., Bagby, G.J., Diehl, A.M. Antibodies to tumor necrosis factor-alpha inhibit liver regeneration after partial hepatectomy. Am J Phsiol, 1992, 263: 579-585.
  • Wu, Y.L., Jiang, Y.Z., Jin, X.J., Lian, L.H., Piao, J.Y., Wan, Y., Jin, H.R., Joon, J., Nan, J.X. Acanthoic acid, a diterpene in Acanthopanax koreanum, protects acetaminophen- induced hepatic toxicity in mice. Phytomedicine, 2010, 17: 475-479.
  • Yan, S.L., Wu, S.T., Yin, M.C., Chen, H.T., Chen, H.C. Protective effects from carnosine and histidine on acetaminophen-induced liver injury. J Food Sci, 2009, 74: 259- 265.
  • Cressman, D.E., Greenbaum, L.E.,, DeAngelis, R.A,., et al., “Liver failure and defective hepatocyte regeneration in interleukin-6-deficient mice,” Science. 1996, 1: 1379–1383.
  • Tai, M., Zhang, J., Song, S., Miao, R., Liu, S., Pang, Q., Wu, Q., Liu, C. Protective effects of luteolin against acetaminophen-induced acute liver failure in mouse. Int Immunopharmacol. 2015, 27: 164-170.
  • Shoeib, A.M., Said, E., Ammar, E.M. Cytoprotective potential of tiron and methyl palmitate against acetaminophen-induced acute liver injury. Can J Physiol Pharmacol. 2015, 20: 1-8.

Investigation of the Effects of Resveratrol on Paracetamol Toxicity Established in Hep3B Cells

Yıl 2023, Cilt: 6 Sayı: 3, 288 - 301, 20.12.2023
https://doi.org/10.38001/ijlsb.1357213

Öz

Aim: We therefore wanted to investigate acetaminophen hepatotoxicity by using Hep3B human hepatoma cells exposed to acetaminophen and resveratrol, used as a protective agent. Specifically, we studied the role of some proinflammatory markers and oxidative damage as possible mechanisms of acetaminophen-associated cytotoxicity.
Materials and Method: The Hep3B human hepatoma cell line was used for this study. In vitro studies (GSH, SOD, CAT, AST, ALT, TNF-alpha, IL-6 and cell viability) were performed by using different methods such as Biochemical analyzer, RT-PCR, ELISA and MTT. Acetaminophen and resveratrol were applied to cells in a different time and doses.
Results: Only acetaminophen treatment decreased SOD, CAT and GSH levels in Hep3B cells whereas acetaminophen and resveratrol co-treatment increased these enzymes levels. On the other hand, acetaminophen and resveratrol co-treatment (especially 160 µM dose of resveratrol) lead a severe increase in TNF-alpha and IL-6 levels.
Conclusion: It is shown that acetaminophen has caused hepatotoxicity but interestingly but resveratrol treatment effects the related parameters mentioned above. Only, acetaminophen administration may cause abnormal decreases and/or increases in antioxidant enzymes and proinflammatory cytokines levels. Additionally, acetaminophen and high dose resveratrol co-treatment triggered the inflammation and oxidative stress. These results showed that resveratrol have a potential to be an effective agent on the treatment and protection of hepatic damage.

Kaynakça

  • Yapar, K., Kart, A., Karapehlivan, M., Atakisi, O., Tunca, R., Erginsoy, S., Citil, M. Hepatoprotective effect of L-carnitine against acute acetaminophen toxicity in mice, Exp Toxicol Pathol, 2007, 59: 121-8.
  • James, L.P., Mayeux, P.R., Hinson, J.A. Acetaminophen-induced hepatotoxicity. Drug metabolism and disposition: The biological fate of chemicals, 2003, 31: 1499- 1506.
  • Boobis, A.R., Seddon, C.E., Nasseri-Sina, P., Davies, D.S. Evidence for a direct role of intracellular calcium in paracetamol toxicity. Biochem Pharmacol, 1990, 39: 1277-1281.
  • Donnelly, P.J., Walker, R.M., Racz, W.J. Inhibition of mitochondrial respiration in vivo is an early event in acetaminophen-induced hepatotoxicity. Arch Toxicol, 1994, 68: 110-118.
  • Russmann, S., Ublick, A.G., Grattagliano, I. “Current consepts of mechanizms in drug-induced hepatotoxicity,” Curr Med Chem, 2009, 16, 2041–3053.
  • Castel, J.V., Jose, M., Ponsoda, X., Bort, R. “In vitro investigation of the molecular mechanisms of hepatotoxicity,” Invitro Meth Pharma Res, 1996, 13, 376-389.
  • BedÊ, T.P., Jesuz, V.A., Souza, V.R., Elias, M.B., Oliveira, F.L., Dias, J.F., Teodoro, A.J., Azeredo, V.B. Effects of Grape Juice, Red Wine and Resveratrol on Liver Parameters of Rat Submitted High-fat Diet. An. Acad. Bras. Cienc. 2020, 92.
  • Wine and Resveratrol on Liver Parameters of Rat Submitted High-fat Diet. An. Acad. Bras. Cienc. 2020, 92, e20191230. Fremont, L. Biological Effects of Resveratrol. Life Sciences, 1999, 66: 663-673.
  • Marques, F.Z., Markus, M.A, Morris, B.J. Resveratrol: Cellular actions of a potent natural chemical that confers a diversity of health benefits. Int. J. Biochem. Cell Biol. 2009, 41, 2125-2128.
  • Karabulut, A.B. Resveratrol ve Etkileri. Türkiye klinikleri J Med Sci, 2008, 28: 166-169.
  • Baur, J.A,. and Sinclair, D.A. Therapeutic potential of resveratrol: the in vivo evidence. Nat Rev Drug Discov, 2006, 5: 493–506.
  • Csiszar, A., Smith, K., Labinskyy, N. Resveratrol attenuates TNF- induced activation of coronary arterial endothelial cells: role of NF-kB inhibition. Am J Physiol Heart Circ Physiol. 2006, 291:1694-1699.
  • Baur, J.A., Singh, G., Srivastava, R.K., Chemoprevention by Resveratrol: Molecular Mechanisms and Therapeutic Potential. Front. Biosci. 2007, 12, 4839-4854.
  • Shakibaei, M., Harikumar, K.B., Aggarwal, B.B. Resveratrol Addiction: To Die or not to Die. Mol.Nutr.Food Res. 2009, 53,115-128.
  • Bernal, W., Wendon, J., Rela, M., Heaton, N., Williams, R. Use and outcome of liver transplantation in acetaminophen-induced acute liver failure. Hepatology, 1998, 27: 1050-1055.
  • Spooner, J.B., Harvey, J.G. The history and usage of paracetamol. J Int Med Res, 1976, 4: 1-6.
  • Newson, R.B., Shaheen, S.O., Chinn, S., Burney, P.G. Paracetamol sales and atopic disease in children and adults: an ecological analysis. Eur Respir J, 2000, 16: 817- 823.
  • Larson, A.M. Acetaminophen hepatotoxicity. Clin Liver Dis, 2007, 11: 525-548.
  • Swierkosz, T.A., Jordan, L., McBride, M., McGough, K., Devlin, J., Botting, RM. Actions of paracetamol on cyclooxygenases in tissue and cell homogenates of mouse and rabbit. Med Sci Monit, 2002, 8: 496-503.
  • Drotman, R.B., Lawhorn, G.T. Serum enzymes as indicators of chemically induced liver damage. Drug Chem Toxicol, 1978, 1: 163-171.
  • Janbaz, K.H., Saeed, S.A., Gilani, A.H. Protective effect of rutin on paracetamol- and CCl4-induced hepatotoxicity in rodents. Fitoterapia, 2002, 73: 557-563.
  • Ali, B.H., Bashir, A.K., Rasheed, R.A. Effect of the traditional medicinal plants Rhazya stricta Balanitis aegyptiaca and Haplophlyum tuberculatum on paracetamol-induced hepatotoxicity in mice. Phytotherapy Res, 2001, 15: 598-603.
  • Rabinovitz, M., Van, D.H. Hepatotoxicity of nonsteroidal anti-inflammatory drugs. Am J gastroenterol, 1992, 87: 1696-1704.
  • Upadhyay, G., Singh, A.K, Kumar, A., Prakash, O., Singh, M.H. Resveratrol Modulates Pyrogallol-induced Changes in Hepatic Toxicity Markers, Xenobiotic Metabolizing Enzymes and Oxidative Stress. Eur. J. Pharmacol. 2008, 596, 146-152.
  • Anundi, I., Lahteenmaki, T., Rundgren, M., Moldeus, P., Lindros, KO. Zonation of acetaminophen metabolism and cytochrome P450 2E1-mediated toxicity studied in isolated periportal and perivenous hepatocytes. Biochem Pharmacol, 1993, 45: 1251-1259.
  • Atkuri, K.R., Mantovani, J.J., Herzenberg, L.A. N-Acetylcysteine a safe antidote for cysteine/glutathione deficiency. Curr Opin Pharmacol, 2007, 7: 355-359.
  • Manda, K. Role of β-carotene against acetaminophen-induced hepatotoxicity in mice. Nutrition Res, 2003, 23: 1097-1103.
  • Yapar, K., Kart, A., Karapehlivan, M., Atakisi, O., Tunca, R., Erginsoy, S., Citil, M. Hepatoprotective effect of L-carnitine against acute acetaminophen toxicity in mice. Exp Toxicol Pathol, 2007, 59: 121-128.
  • Topic, B., Tani, E., Tsiakitzis, K., Kourounakis, P.N., Dere, E, Hasenohrl R.U, Hacker R, Mattern, C.M., Huston, J.P. Enhanced maze performance and reduced oxidative stress by combined extracts of zingiber officinale and ginkgo biloba in the aged rat. Neurobiol aging, 2002, 23: 135-143.
  • Brand, M.D., Affourtit, C., Esteves, T.C., Green, K., Lambert, A.J., Miwa, S., Pakay, J.L., Parker, N. Mitochondrial superoxide: production, biological effects, and activation of uncoupling proteins. Free rad biol med, 2004, 37: 755-767.
  • Gao, H., Zhou, Y.W. Anti-lipid peroxidation and protection of liver mitochondria against injuries by picroside II. World J Gastroenterol, 2005, 11: 3671-3674.
  • Olaleye, M.T., Rocha, B.T. Acetaminophen-induced liver damage in mice: effects of some medicinal plants on the oxidative defense system. Exp toxicol pathol, 2008, 59: 319-327.
  • Xu, H., Lin, L., Yuan, W.J. Antiarrhythmic effect of endothelin-A receptor antagonist on acute ischemic arrhythmia in isolated rat heart. Acta Pharmacol Sin, 2003, 24: 37-44.
  • Ozdemir, R., Parlakpinar, H., Polat, A., Colak, C., Ermis, N., Acet, A. Selective endothelin a (ETA) receptor antagonist (BQ-123) reduces both myocardial infarct size and oxidant injury. Toxicology, 2006, 219: 142-149.
  • Chularojmontri, L., Wattanapitayakul, S.K., Herunsalee, A., Charuchongkolwongse, S., Niumsakul, S., Srichairat, S. Antioxidative and cardioprotective effects of Phyllanthus urinaria L. on doxorubicin-induced cardiotoxicity. Biol Pharm Bull, 2005, 28: 1165-1171.
  • Awodele, O., Yemitan, O., Ise, P.U., Ikumawoyi, V.O. Modulatory potentials of aqueous leaf and unripe fruit extracts of Carica papaya Linn. (Caricaceae) against carbontetrachloride and acetaminophen-induced hepatotoxicity in rats. J Intercult Ethnopharmacol. 2016, 5: 27-35.
  • Uysal, H.B., Dağlı, B., Yılmaz, M., Kahyaoğlu, F., Gökçimen, A., Ömürlü, İ.K., Demirci, B. Biochemical and histological effects of thiamine pyrophosphate against acetaminophen-ınduced hepatotoxicity. Basic Clin Pharmacol Toxicol. 2016, 118: 70-6.
  • Malhi, H., Gores, G.J., Lemasters, J.J. Apoptosis and necrosis in the liver: a tale of two deaths? Hepatology, 2006, 43: 31-44.
  • Akerman, P,, Cote, P., Yang, SQ., McClain, C., Nelson, S., Bagby, G.J., Diehl, A.M. Antibodies to tumor necrosis factor-alpha inhibit liver regeneration after partial hepatectomy. Am J Phsiol, 1992, 263: 579-585.
  • Wu, Y.L., Jiang, Y.Z., Jin, X.J., Lian, L.H., Piao, J.Y., Wan, Y., Jin, H.R., Joon, J., Nan, J.X. Acanthoic acid, a diterpene in Acanthopanax koreanum, protects acetaminophen- induced hepatic toxicity in mice. Phytomedicine, 2010, 17: 475-479.
  • Yan, S.L., Wu, S.T., Yin, M.C., Chen, H.T., Chen, H.C. Protective effects from carnosine and histidine on acetaminophen-induced liver injury. J Food Sci, 2009, 74: 259- 265.
  • Cressman, D.E., Greenbaum, L.E.,, DeAngelis, R.A,., et al., “Liver failure and defective hepatocyte regeneration in interleukin-6-deficient mice,” Science. 1996, 1: 1379–1383.
  • Tai, M., Zhang, J., Song, S., Miao, R., Liu, S., Pang, Q., Wu, Q., Liu, C. Protective effects of luteolin against acetaminophen-induced acute liver failure in mouse. Int Immunopharmacol. 2015, 27: 164-170.
  • Shoeib, A.M., Said, E., Ammar, E.M. Cytoprotective potential of tiron and methyl palmitate against acetaminophen-induced acute liver injury. Can J Physiol Pharmacol. 2015, 20: 1-8.
Toplam 44 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Konular Yapısal Biyoloji , Biyokimya ve Hücre Biyolojisi (Diğer)
Bölüm Araştırma Makaleleri
Yazarlar

Alpgiray Turgut 0000-0003-2461-5125

Tubanur Aslan Engin 0000-0003-2885-8829

Muhammet Turgut 0009-0001-7916-167X

Mesut Halıcı 0000-0002-7473-2955

Erken Görünüm Tarihi 1 Aralık 2023
Yayımlanma Tarihi 20 Aralık 2023
Yayımlandığı Sayı Yıl 2023 Cilt: 6 Sayı: 3

Kaynak Göster

EndNote Turgut A, Aslan Engin T, Turgut M, Halıcı M (01 Aralık 2023) Investigation of the Effects of Resveratrol on Paracetamol Toxicity Established in Hep3B Cells. International Journal of Life Sciences and Biotechnology 6 3 288–301.


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