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Effect of Resveratrol on Total Oxidative-Antioxidative Status and DNA Damage in Rats Induced Methotrexate

Yıl 2022, Cilt 7, Sayı 2, 84 - 91, 31.08.2022
https://doi.org/10.51754/cusbed.1056908

Öz

In this study, the effects of resveratrol (RES) on leukocyte percentages, total oxidant (TOS) -antioxidan status (TAS) and DNA damage (8-OHDG) were investigated in rats induced by methotrexate (MTX). The rats used in the study were randomly divided into 4 groups each consisting of 10 rats.Control group , MTX group (20 mg / kg ip, once a week, for two weeks) ,RES group (40 mg / kg / day orally, for two weeks), MTX + RES group (20 mg / kg ip, once a week and 40 mg / kg / day orally for 2 weeks)At the end of the experiment, blood samples were taken from the hearts of the rats and the percentage of leukocyte (neutrophil, eosinophil, basophil, lymphocyte, monocyte) was examined by classical methods. The levels of TOS and TAS were measured by colorimetric kits and 8-OHDG level by ELISA kit. Neutrophil (p≤0.05) and monocyte (p≤0.01) percentages of MTX and MTX + RES groups were found to be statistically lower than control and RES groups. There was also a significant increase in TOS and OSI levels (p <0.001) and a significant decrease in TAS level (p <0.05) in the MTX group. In the MTX + RES group, the positive statistical significance of these parameters was determined. Changes in eosinophil, basophil, lymphocyte percentages were statistically insignificant. In conclusion, it can be said that the RES treatment for neutropenia and monocytopenia caused by MTX can not be effective but may be effective in reducing oxidative stress.

Kaynakça

  • Abdel-Wahaba BA, Abdel-Wahab MM (2016). Protective effect of resveratrol against chronic intermittent hypoxia-induced spatial memory deficits, hippocampal oxidative DNA damage and increased p47Phox NADPH oxidase expression in young rats. Behav Brain Res, 305, 65–75.
  • Aggrawal B, Shishodia S (2005). Resveratrol: A polyphenol for all season. Resveratrol in Health and Disease. University of Texas M. D. Anderson Cancer Center, CRC Press, Taylor and Francis group, 1, 70, 1-16.
  • Akkuş Ö, Şanlı K (2006). Kanserli çocuklarda hemşirelik bakımı ve desteğinin önemi. Uyar M, Uslu R, Yıldırım Y.K, editör. Kanser ve palyatif bakım. İzmir: Meta Basım Matbaacılık, 309-19.
  • Alturfan AA, Tozan-Beceren A, Sehirli AO, Demiralp E, Sener G, Omurtag GZ (2011). Resveratrol ameliorates oxidative DNA damage and protects against acrylamide-induced oxidative stress in rats. Mol Biol Rep, 39, 4, 4589-4596.
  • Aribal-Kocatürk P, Kavas GÖ, Büyükkağnıcı Dİ (2007). Pretreatment effect of resveratrol on streptozotocin-induced diabetes in rats. Biol Trace Elem Res, 118, 3, 244–249.
  • Armağan İ (2015). Metotreksat’ın karaciğer ve böbrekte neden olduğu hasarda oksidatif stresin rolü. SDÜ Tıp Fak Derg, 22, 4, 151-155.
  • Atmaca N, Atmaca HT, Kanici A, Anteplioğlu (2014). Protective effect of resveratrol on sodium fluoride-induced oxidative stress, hepatotoxicity and neurotoxicity in rats Food and Chemical Toxicology, 70: 191–197
  • Babiak RM, Campello AP, Carnieri EG, Oliveira MB (1998). Methotrexate: Pentose Cycle And Oxidative Stres. Cell. Biochem. Funct. 6: 283-293.
  • Blijlevens N, Sonis S (2007). Palifermin (Recombinant Keratinocyte Growth Factor-1): A Pleiotropic Growth Factor With Multiple Biological Activities In Preventing Chemotherapy- And Radiotherapy-Induced Mucositis. Ann. Oncol. 18: 817-826.
  • Block KI, Koch AC, Mead MN, Tothy PK, Newman RA, Gyllenhaal C (2007). Impact of antioxidant suplementation on chemotherapeutic efficacy: A systematic review of the evidence from randomized controlled trials. Cancer Treat Rev, 33, 5, 407-418.
  • Bozkurt M, Em S, Oktayoglu P, Turkcu G, Yuksel H, Sarıyıldız MA, Caglayan M, Batmaz İ, Nas K, Bozkurt Y, Kuyumcu M (2014). Carvacrol prevents methotrexateinduced renal oxidative injury and renal damage in rats Clin In_est Med, 37 (1): E19-E25.
  • Burkitt MJ, Duncan J (2000). Effects of trans-resveratrol on copper-dependent hydroxylradical formation and DNA damage: evidence for hydroxyl-radical scavenging and a novel, glu-tathione-sparing mechanism of action. Arch Biochem Biophys, 15, 381, 2, 253-263
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  • Caron, J. E., Krull, K. R., Hockenberry, M., Jain, N., Kaemingk, K., Moore, I. M. (2009). Oxidative stress and executive function in children receiving chemotherapy for acute lymphoblastic leukemia. Pediatric Blood and Cancer, 53(4), 551-556.
  • Cetinkaya A, Kurutas EB, Bulbuloglu E, Kantarceken B (2007). The effects of Nacetylcysteine on methotrexate-induced oxidative renal damage in rats. Nephrol Dial Transplant. 22, 1, 284-285.
  • Comba B, Cinar A, Comba A, Gencer YG, 2016a. Effects of ACTH application on kidney function tests, the electrolytes and hematological parameters in rats. Ankara Üniversitesi Veteriner Fakültesi Dergisi, 63 (3), 229-233.
  • Comba B, Mis L, Uslu S, Comba A (2017). The effect of barley grass on antioxidant capacity and DNA damage in rat with renal failure - Fresenius Environmental Bulletin, 26 10, 6135-6140.
  • Comba A, Oto G, Comba B, Ozdemir H, Keskin S, Akveran Aslan G, 2020. Effects of boric acid on proinflammation cytokines, total oxidative antioxidative status and hematological parameters in rats applied benzo(a)pyrene, Fresenıus Envıronmental Bulletin, 29(5)3599-3605.
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  • Çelebi S (2003). Çocuklarda Febril Nötropeni, UÜ Tıp Fak Derg; 29, 2, 35-41.
  • Çetin A, Kaynar L, Koçyiğit İ, Kabukçu Hacıoğlu S, Saraymen R, Ozturk A, Ismail Sari, Sagdic O (2008). Role of grape seed extract on methotrexate ınduced oxidative stress in rat liver The American Journal of Chinese Medicine, Vol. 36, No. 5, 861–872.
  • Dalaklioğlu S, Genç G.E, Aksoy N.H, Akçit F, Gümüşlü S (2013). Resveratrol ameliorates methotrexate-induced hepatotoxicity in rats via inhibition of lipid peroxidation. Human and Experimental Toxicology, The Author(s), 32(6), 662–671.
  • Dilek K (2002). Günümüzde en sık kullanılan antisupresif ajanların özellikleri. Ankem Derg, 16, 3, 199-202.
  • Dong Z (2003). Molecular mechanism of the chemopreventive effect of resveratrol. Mutat Res, 523-524, 145-150.
  • Duman TT, Üstün C, Şavlı H (2014). Hatalı Metotreksat Kullanımı Sonucu Gelişen Nötropenik Ateş. Ankem Antibiyotik ve Kemoterapi Kongresi, Bodrum. Ankem Derg, 28 (Ek 1)
  • Emılia-Juan M, Pilar-Vinardell M, Joana M (2002). The daily oral administration of high doses of trans-resveratrol to rats for 28 days is not harmful. J. Nutr, 132: 257–260.
  • Erel O (2004). A novel automated method to measure total antioxidant response against potent free radical reactions. Clin Biochem, 37, 112-119.
  • Erel O (2005). A new automated colorimetric method for measuring total oxidant status. J Clin Biochem, 47, 119-129.
  • Fontacave M, Lepoivre M, Elleilgant E, Gerez C, Guittet O (1998). Resveratrol, a remarkable inhibitor of ribonucleotide reductase, FEBS Lett, 421, 277-279.
  • Hadi NR, Al-Amran FG, Swadi A (2012). Metformin ameliorates methotrexate-induced hepatotoxicity.J Pharmacol Pharma-cother, 3: 248-53.
  • Hempel L, Misselwitz J, Fleck C, Kentouche K, Leder C, Appenroth D et al. (2003) In_uence of high-dose methotrexate therapy (HD-MTX) on glomerular and tubular kidney function. Medical and pediatric oncology, 40(6): 348-54.
  • Hung LM, Chen JK, Huang SS, Lee RS, Su MJ (2000). Cardioprotective effect of resveratrol, a natural antioxidant derived from grapes. Cardiovasc Res, 18, 47(3), 549-55.
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  • Jahovic N, Cevik H, Sehirli AO, Yegen BC, Sener G (2003). Melatonin prevents methotrexate-induced hepatorenal oxidative injury in rats. Journal of pineal research, 34(4): 282-7.
  • Kasdallah-Grissa A, Mornagui B, Aouani E, Hammami M, El May M, Gharbi N, Kamoun A, El-Fazaa S (2007). Resveratrol, a red wine polyphenol, attenuates ethanol-induced oxidative stress in rat liver. Life Sci, 80: 1033–1039.
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Resveratrolün Metotreksat Uygulanan Ratlarda Total Oksidan-Antioksidan Durumuna ve DNA Hasarına Etkisi

Yıl 2022, Cilt 7, Sayı 2, 84 - 91, 31.08.2022
https://doi.org/10.51754/cusbed.1056908

Öz

Bu çalışmada resveratrolün (RES) metotreksat (MTX) uygulanan ratlarda lökosit yüzdelerine, total oksidan (TOS)-antioksidan durumuna (TAS) ve DNA hasarına (8-OHdG) etkisi araştırıldı. Çalışmada kullanılan ratlar rastgele her biri 10 rattan oluşan 4 gruba ayrıldı. Gruplar, kontrol grubu, MTX grubu (20 mg/kg i.p., haftada 1 kez, iki hafta), RES grubu (40 mg/kg/gün oral, 14 gün) MTX+RES grubu (20 mg/kg i.p, haftada 1 kez, iki hafta ve 40 mg/kg/gün oral, 14 gün) olarak oluşturuldu. Deneme sonunda ratların kalplerinden kan örnekleri alındı, lökosit (nötrofil, eozinofil, bazofil, lenfosit, monosit) yüzdelerine klasik yöntemlerle, TOS, TAS, değerlerine kolorimetrik kitlerle, 8-OHdG seviyesine ELISA kiti ile bakıldı. MTX ve MTX+RES gruplarındaki nötrofil (p≤0.05) ve monosit (p≤0.01) yüzdeleri kontrol ve RES grubuna göre istatistiksel önemde daha düşük olduğu belirlendi. Ayrıca, MTX grubundaki, TOS ve OSI seviyelerinde anlamlı bir artış (p<0.001), TAS seviyesinde anlamlı bir azalma (p<0.05) bulundu. MTX+RES grubundaki ratlarda ise bu parametrelerin istatistiksel önemde iyileştiği belirlendi. Eozinofil, bazofil, lenfosit yüzdelerindeki değişimler istatistiksel olarak önemsizdi. Sonuç olarak, MTX in neden olduğu nötropeni ve monositopeninin iyileştirilmesinde RES’ in etkili olamayacağını fakat oksidatif stresi azaltmada etkili olabileceğini söyleyebiliriz.

Kaynakça

  • Abdel-Wahaba BA, Abdel-Wahab MM (2016). Protective effect of resveratrol against chronic intermittent hypoxia-induced spatial memory deficits, hippocampal oxidative DNA damage and increased p47Phox NADPH oxidase expression in young rats. Behav Brain Res, 305, 65–75.
  • Aggrawal B, Shishodia S (2005). Resveratrol: A polyphenol for all season. Resveratrol in Health and Disease. University of Texas M. D. Anderson Cancer Center, CRC Press, Taylor and Francis group, 1, 70, 1-16.
  • Akkuş Ö, Şanlı K (2006). Kanserli çocuklarda hemşirelik bakımı ve desteğinin önemi. Uyar M, Uslu R, Yıldırım Y.K, editör. Kanser ve palyatif bakım. İzmir: Meta Basım Matbaacılık, 309-19.
  • Alturfan AA, Tozan-Beceren A, Sehirli AO, Demiralp E, Sener G, Omurtag GZ (2011). Resveratrol ameliorates oxidative DNA damage and protects against acrylamide-induced oxidative stress in rats. Mol Biol Rep, 39, 4, 4589-4596.
  • Aribal-Kocatürk P, Kavas GÖ, Büyükkağnıcı Dİ (2007). Pretreatment effect of resveratrol on streptozotocin-induced diabetes in rats. Biol Trace Elem Res, 118, 3, 244–249.
  • Armağan İ (2015). Metotreksat’ın karaciğer ve böbrekte neden olduğu hasarda oksidatif stresin rolü. SDÜ Tıp Fak Derg, 22, 4, 151-155.
  • Atmaca N, Atmaca HT, Kanici A, Anteplioğlu (2014). Protective effect of resveratrol on sodium fluoride-induced oxidative stress, hepatotoxicity and neurotoxicity in rats Food and Chemical Toxicology, 70: 191–197
  • Babiak RM, Campello AP, Carnieri EG, Oliveira MB (1998). Methotrexate: Pentose Cycle And Oxidative Stres. Cell. Biochem. Funct. 6: 283-293.
  • Blijlevens N, Sonis S (2007). Palifermin (Recombinant Keratinocyte Growth Factor-1): A Pleiotropic Growth Factor With Multiple Biological Activities In Preventing Chemotherapy- And Radiotherapy-Induced Mucositis. Ann. Oncol. 18: 817-826.
  • Block KI, Koch AC, Mead MN, Tothy PK, Newman RA, Gyllenhaal C (2007). Impact of antioxidant suplementation on chemotherapeutic efficacy: A systematic review of the evidence from randomized controlled trials. Cancer Treat Rev, 33, 5, 407-418.
  • Bozkurt M, Em S, Oktayoglu P, Turkcu G, Yuksel H, Sarıyıldız MA, Caglayan M, Batmaz İ, Nas K, Bozkurt Y, Kuyumcu M (2014). Carvacrol prevents methotrexateinduced renal oxidative injury and renal damage in rats Clin In_est Med, 37 (1): E19-E25.
  • Burkitt MJ, Duncan J (2000). Effects of trans-resveratrol on copper-dependent hydroxylradical formation and DNA damage: evidence for hydroxyl-radical scavenging and a novel, glu-tathione-sparing mechanism of action. Arch Biochem Biophys, 15, 381, 2, 253-263
  • Can G (2003). Kanser kemoterapi rehberi ve uygulamaya yönelik öneriler. Editörler; Durna Z, Aydıner A, Istanbul, Nobel tıp Kitapevleri.
  • Caron, J. E., Krull, K. R., Hockenberry, M., Jain, N., Kaemingk, K., Moore, I. M. (2009). Oxidative stress and executive function in children receiving chemotherapy for acute lymphoblastic leukemia. Pediatric Blood and Cancer, 53(4), 551-556.
  • Cetinkaya A, Kurutas EB, Bulbuloglu E, Kantarceken B (2007). The effects of Nacetylcysteine on methotrexate-induced oxidative renal damage in rats. Nephrol Dial Transplant. 22, 1, 284-285.
  • Comba B, Cinar A, Comba A, Gencer YG, 2016a. Effects of ACTH application on kidney function tests, the electrolytes and hematological parameters in rats. Ankara Üniversitesi Veteriner Fakültesi Dergisi, 63 (3), 229-233.
  • Comba B, Mis L, Uslu S, Comba A (2017). The effect of barley grass on antioxidant capacity and DNA damage in rat with renal failure - Fresenius Environmental Bulletin, 26 10, 6135-6140.
  • Comba A, Oto G, Comba B, Ozdemir H, Keskin S, Akveran Aslan G, 2020. Effects of boric acid on proinflammation cytokines, total oxidative antioxidative status and hematological parameters in rats applied benzo(a)pyrene, Fresenıus Envıronmental Bulletin, 29(5)3599-3605.
  • Comba B, Oto G, Mis L, Özdemir H, Comba A 2016b. Effects of borax on inflammation, haematological parameters and total oxidant-antioxidant status in rats applied 3–methylcholanthrene - Kafkas Univ Vet Fak Derg, , 22, 4 539-544
  • Çelebi S (2003). Çocuklarda Febril Nötropeni, UÜ Tıp Fak Derg; 29, 2, 35-41.
  • Çetin A, Kaynar L, Koçyiğit İ, Kabukçu Hacıoğlu S, Saraymen R, Ozturk A, Ismail Sari, Sagdic O (2008). Role of grape seed extract on methotrexate ınduced oxidative stress in rat liver The American Journal of Chinese Medicine, Vol. 36, No. 5, 861–872.
  • Dalaklioğlu S, Genç G.E, Aksoy N.H, Akçit F, Gümüşlü S (2013). Resveratrol ameliorates methotrexate-induced hepatotoxicity in rats via inhibition of lipid peroxidation. Human and Experimental Toxicology, The Author(s), 32(6), 662–671.
  • Dilek K (2002). Günümüzde en sık kullanılan antisupresif ajanların özellikleri. Ankem Derg, 16, 3, 199-202.
  • Dong Z (2003). Molecular mechanism of the chemopreventive effect of resveratrol. Mutat Res, 523-524, 145-150.
  • Duman TT, Üstün C, Şavlı H (2014). Hatalı Metotreksat Kullanımı Sonucu Gelişen Nötropenik Ateş. Ankem Antibiyotik ve Kemoterapi Kongresi, Bodrum. Ankem Derg, 28 (Ek 1)
  • Emılia-Juan M, Pilar-Vinardell M, Joana M (2002). The daily oral administration of high doses of trans-resveratrol to rats for 28 days is not harmful. J. Nutr, 132: 257–260.
  • Erel O (2004). A novel automated method to measure total antioxidant response against potent free radical reactions. Clin Biochem, 37, 112-119.
  • Erel O (2005). A new automated colorimetric method for measuring total oxidant status. J Clin Biochem, 47, 119-129.
  • Fontacave M, Lepoivre M, Elleilgant E, Gerez C, Guittet O (1998). Resveratrol, a remarkable inhibitor of ribonucleotide reductase, FEBS Lett, 421, 277-279.
  • Hadi NR, Al-Amran FG, Swadi A (2012). Metformin ameliorates methotrexate-induced hepatotoxicity.J Pharmacol Pharma-cother, 3: 248-53.
  • Hempel L, Misselwitz J, Fleck C, Kentouche K, Leder C, Appenroth D et al. (2003) In_uence of high-dose methotrexate therapy (HD-MTX) on glomerular and tubular kidney function. Medical and pediatric oncology, 40(6): 348-54.
  • Hung LM, Chen JK, Huang SS, Lee RS, Su MJ (2000). Cardioprotective effect of resveratrol, a natural antioxidant derived from grapes. Cardiovasc Res, 18, 47(3), 549-55.
  • Ignatowicz, E., Bear-Dubowska, W., 2001. Resveratrol, a natural chemopreventive agent against degenerative diseases. Pol. J. Pharmacol, 53: 557–569.
  • Jahovic N, Cevik H, Sehirli AO, Yegen BC, Sener G (2003). Melatonin prevents methotrexate-induced hepatorenal oxidative injury in rats. Journal of pineal research, 34(4): 282-7.
  • Kasdallah-Grissa A, Mornagui B, Aouani E, Hammami M, El May M, Gharbi N, Kamoun A, El-Fazaa S (2007). Resveratrol, a red wine polyphenol, attenuates ethanol-induced oxidative stress in rat liver. Life Sci, 80: 1033–1039.
  • Kaya E, Yılmaz S. (2020). Deneysel Olarak Metotreksat Uygulanmış Ratlarda Oksidatif Stres ve Antioksidan Enzim Aktiviteleri Üzerine Enginar Uygulamasının Etkisi]. F.Ü.Sağ.Bil.Vet.Derg. 34 (1): 43 - 47
  • Kaynar L, Çetin A, Hacıoğlu KS, Eser B, Koçyiğit S, Canöz Ö, Taşdemir A, Karadağ C, Kurnaz F, Saraymen R, Silici S (2012). Effıcacy of royal jelly on Methotrekxate-Induced systemic Oxıdatıve Stress and Damage to small ıntestıne rats, Afr J Tradit Complement Altern Med. 9(3): 412-417.
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Ayrıntılar

Birincil Dil Türkçe
Konular Veteriner Hekimlik
Bölüm Araştırma Makalesi
Yazarlar

Mehmet VADİ>
İNÖNÜ ÜNİVERSİTESİ, TURGUT ÖZAL TIP MERKEZİ
0000-0002-0207-1430
Türkiye


Bahat COMBA> (Sorumlu Yazar)
HİTİT ÜNİVERSİTESİ
0000-0002-3419-4144
Türkiye

Destekleyen Kurum Yüzüncü Yıl Üniversitesi Bilimsel Araştırma Proje başkanlığı
Proje Numarası 2015-SBE-YL235
Teşekkür Yüzüncü Yıl Üniversitesi Bilimsel Araştırma Proje başkanlığına desteklerinden dolayı teşekkür ederiz.
Erken Görünüm Tarihi 29 Ağustos 2022
Yayımlanma Tarihi 31 Ağustos 2022
Yayınlandığı Sayı Yıl 2022, Cilt 7, Sayı 2

Kaynak Göster

APA Vadi, M. & Comba, B. (2022). Resveratrolün Metotreksat Uygulanan Ratlarda Total Oksidan-Antioksidan Durumuna ve DNA Hasarına Etkisi . Cumhuriyet Üniversitesi Sağlık Bilimleri Enstitüsü Dergisi , 7 (2) , 84-91 . DOI: 10.51754/cusbed.1056908

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