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Nephroprotective effect of Resveratrol against Methotrexate -induced renal toxicity in female rats

Yıl 2022, Cilt: 10 Sayı: 2, 123 - 133, 26.08.2022

Şükriye Yeşilot Meltem Özgöçmen

https://doi.org/10.24998/maeusabed.1136994

Öz

The study purposed to appraise the nephroprotective effects of resveratrol-(RES) in relation to methotrexate-(MTX)-induced renal toxicity in female rats. The animals were allocated into three groups with six in each group: control, MTX:(15 mg/kg, only a dose, i.p), MTX+RES group: (15 mg/kg MTX, only a dose, i.p + 20 mg/kg RES, only a dose daily, oral gavage, 7 days). The nephroprotective efficacy was interpreted by measuring biochemical parameters such as serum renal function markers (uric acid, BUN and creatinine), total oxidant (TOS) and antioxidant status (TAS) in renal homogenates. Moreover, the effect of RES on kidneys was appraised by histopathological and immunohistochemical analyzes. In MTX-induced rats, RES treatment exhibited its nephroprotective effects with a significant increase in renal TAS as well as a significant decrease in serum BUN and renal TOS levels. In parallel with the biochemical data, it was observed that RES had a protective effect in the histological staining findings. Immunohistochemically, it was determined that TNF-α, one of the indicators of systemic inflammatory response, decreased with RES-treatment. The findings of the study show that RES administration 1 hour before MTX injection to rats has a curative effect on renal damage.

Anahtar Kelimeler

Methotrexate Resveratrol Renal toxicity female rats

Kaynakça

  • Abdel-Raheem, I.T., Khedr, N.F., 2014. Renoprotective effects of montelukast, a cysteinyl leukotriene receptor antagonist, against methotrexate-induced kidney damage in rats, Naunyn Schmiedebergs Arch. Pharmacol. 387;341–353, http://dx.doi.org/10.1007/s00210-013-0949-x
  • Abouelela, M.E., Orabi, M.A.A., Abdelhamid, R.A., Abdelkader, M.S., Madkor, H.R., Darwish, F.M.M., Hatano, T., Elsadek, B.E.M., 2020. Ethyl acetate extract of Ceiba pentandra (L.) Gaertn. reduces methotrexate-induced renal damage in rats via antioxidant, anti-inflammatory, and antiapoptotic actions. J Tradit Complement Med. 10(5):478-86. https://doi.org/10.1016/j.jtcme.2019.08.006
  • Ahmed, W., Zaki, A.M.R. and Nabil, T., 2015. Prevention of methotrexate-induced nephrotoxicity by concomitantadministration of garlic aqueous extract in rat. Turkish Journal of Medical Sciences. 45(3) 1408-121.
  • Akbel, E., Arslan-Acaroz, D., Demirel, H.H., Kucukkurt, I., Ince, S., 2018. The subchronic exposure to malathion, an organophosphate pesticide, causes lipid peroxidation, oxidative stress, and tissue damage in rats: the protective role of resveratrol, Toxicology Research. 7;3,503–512, https://doi.org/10.1039/c8tx00030a
  • Armagan, I., Bayram, D., Candan, I.A., Yigit, A., Celik, E., Armagan, H.H. et al., 2015. Effects of pentoxifylline and alpha lipoic acid on methotrexate-induced damage in liver and kidney of rats. Environ Toxicol Pharmacol, 39(3);1122-1131
  • Asci, H., Ozmen, O., Ellidag, H.Y., Aydin, B., Bas, E., Yilmaz, N., 2017. The impact of gallic acid on the methotrexate-induced kidney damage in rats. J food drug anal. 25:890–897.
  • Baur, J., Sinclair, D., 2006. Therapeutic potential of resveratrol: the in vivo evidence. Nat Rev Drug Discov 5, 493–506. https://doi.org/10.1038/nrd2060
  • Bay Karabulut A., 2008. Resveratrol and it's effects. Turkiye Klinikleri Journal of Medical Sciences. 28(Suppl):166-169
  • Bedoui, Y., Guillot, X., Sélambarom, J., Guiraud, P., Giry, C., Jaffar-Bandjee, M.C., Ralandison, S., Gasque, P., 2019. Methotrexate an Old Drug with New Tricks. Int. J. Mol. Sci. 20(20):5023. doi: 10.3390/ijms20205023.
  • Baud, L., Ardaillou, R., 1995. Tumor necrosis factor in renal injury. Miner Electrolyte Metab. 21:336–41.
  • Braun, J., Rau, R., 2009. An update on methotrexate. Curr Opin Rheumatol. 21(3):216-23.
  • Brown, V., K. Patel, M. Viskaduraki, et al . 2010. Repeat dose study of the cancer chemopreventive agent resveratrol in healthy volunteers: safety, pharmacokinetics and effect on the insulin-like growth factor axis. Cancer Res. 70: doi. 10.1158/0008-5472.CAN-10-2364.
  • Calamini, B., K. Ratia, M.G. Malkowski, et al . 2010. Pleiotropic mechanisms facilitated by resveratrol and its metabolites. Biochem. J. 429: 273– 282.
  • Chan, E.S.L., Cronstein, B.N., 2013. Mechanisms of action of methotrexate. Bull. NYU Hosp. Jt. Dis. 71:S5–S8
  • Çakır, T., Polat, C., Baştürk, A., Gül, M., Aslaner, A., Durgut, H., Şehirli, A.Ö., Aykaç, A., Bahar, Lç, Sabuncuoglu, M.Z., 2015. The effect of alpha lipoic acid on rat kidneys in methotrexate induced oxidative injury. Eur Rev Med Pharmacol Sci. 19(11):2132-9. PMID: 26125279.
  • Drishya, S., Dhanisha, S. S., & Guruvayoorappan, C., 2022. Antioxidant-rich fraction of Amomum subulatum fruits mitigates experimental methotrexate-induced oxidative stress by regulating TNF-α, IL-1β, and IL-6 proinflammatory cytokines. Journal of Food Biochemistry. 46;e13855. https://doi.org/10.1111/jfbc.13855
  • Elmarakby, A.A. and Sullivan, J.C., 2012. Relationship between Oxidative Stress and Inflammatory Cytokines in Diabetic Nephropathy. Cardiovascular Therapeutics, 30: 49-59. https://doi.org/10.1111/j.1755-5922.2010.00218.x
  • Elmansy, R.A., Seleem, H.S., Mahmoud, A.R., Hassanein, E.H., Ali, F.E., 2021. Rebamipide potentially mitigates methotrexate-induced nephrotoxicity via inhibition of oxidative stress and inflammation: a molecular and histochemical study. Anat Rec. 304:647–661.
  • El-Sheikh, A.A.K., Morsy, M.A. and Al-Taher, A.Y., 2016. Protective mechanisms of resveratrol against methotrexate-induced renal damage may involve BCRP/ABCG2. Fundam Clin Pharmacol, 30: 406-418. https://doi.org/10.1111/fcp.12205
  • El-Sheikh, A.A., Morsy, M.A., Okasha, A.M., 2017. Inhibition of NF-kappaB/TNF-alpha pathway may be involved in the protective effect of resveratrol against cyclophosphamide-induced multi-organ toxicityImmunopharmacol. Immunotoxicol. 39 (4);180-187
  • Erboga, M., Aktas, C., Fidanol Erboga, Z., Bozdemir Donmez, Y. & Gurel, A., 2015. Quercetin ameliorates methotrexate-induced renal damage, apoptosis and oxidative stress in rats, Renal Failure. 37:9, 1492-1497, DOI: 10.3109/0886022X.2015.1074521
  • Fremont, L., 2000. Biological effects of resveratrol.Life Sci.66;663– 673
  • Gaies, E., Jebabli, N., Trabelsi, S., Salouage, I., Charfi, R. et al., 2012. Methotrexate Side Effects: Review Article. J Drug Metab Toxicol 3:125. doi:10.4172/2157-7609.1000125
  • Green, M.R., Chamberlain, M.C., 2009. Renal dysfunction during and after high-dose methotrexate. Cancer Chemother Pharmacol. 63, 599. https://doi.org/10.1007/s00280-008-0772-0
  • Gunyeli, I., Saygin, M. & Ozmen, O.,2021. Methotrexate-induced toxic effects and the ameliorating effects of astaxanthin on genitourinary tissues in a female rat model. Arch Gynecol Obstet 304, 985–997 https://doi.org/10.1007/s00404-021-06000-2
  • Heidari, R., Ahmadi, A., Mohammadi, H., Ommati, M.M., Azarpira, N., Niknahad, H., 2018. Mitochondrial dysfunction and oxidative stress are involved in the mechanism of methotrexate-induced renal injury and electrolytes imbalance, Biomedicine & Pharmacotherapy. 107;834-840.
  • Hobl, E-L., Mader, R.M., Erlacher, L., Duhm, B., Mustak, M., Bröll, H., et al., 2011. The influence of methotrexate on the gene expression of the pro-inflammatory cytokine IL-12A in the therapy of rheumatoid arthritis. Clin Exp Rheumatol. 29:963–969
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Dişi sıçanlarda Resveratrol'ün Metotreksat ile indüklenen renal toksisiteye karşı nefroprotektif etkisi

Yıl 2022, Cilt: 10 Sayı: 2, 123 - 133, 26.08.2022

Şükriye Yeşilot Meltem Özgöçmen

https://doi.org/10.24998/maeusabed.1136994

Öz

Reaktif oksijen türlerinin (ROS) güçlü bir temizleyicisi olan resveratrolün (RES), böbrek hastalıkları da dahil olmak üzere çeşitli metabolik bozukluklara karşı koruyucu etkisi olduğu bildirilmektedir. Bu çalışma, dişi sıçanlarda metotreksat (MTX) ile indüklenen renal toksisitede resveratrolün nefroprotektif etkilerini değerlendirmeyi amaçlamaktadır. Çalışma, her grupta altı adet rat olacak şekilde üç gruba ayrıldı: Kontrol, MTX: (15 mg/kg, tek doz, i.p), MTX + RES grubu: (15 mg/kg MTX, tek doz, i.p + 20 mg/ kg RES, günde tek doz, oral gavaj, 7 gün). Serum renal fonksiyon belirteçleri (ürik asit, BUN ve kreatinin), renal homojenatlarda toplam oksidan (TOS) ve antioksidan durumu (TAS) gibi biyokimyasal parametreler ölçülerek nefroprotektif etkinlik yorumlandı. Ayrıca RES'in böbrekler üzerindeki etkisi histopatolojik ve immünohistokimyasal analizlerle değerlendirildi. MTX ile indüklenen ratlarda RES tedavisi, serum BUN, kreatinin ve renal TOS düzeylerinde anlamlı azalmanın yanında renal TAS'ta anlamlı bir artışla nefro-koruyucu etkilerini gösterdi. Histolojik boyama bulgularında da biyokimyasal verilere paralel olarak, RES’in koruyucu etkisinin olduğu gözlendi. İmmünhistokimyasal olarak sistemik inflamatuar yanıtın göstergelerinden biri olan TNF-α'nın RES tedavisi ile azaldığı belirlendi. Araştırmanın bulguları, ratlara MTX enjeksiyonundan 1 saat önce RES uygulamasının böbrek hasarı üzerinde iyileştirici etkisi olduğunu göstermektedir.

Anahtar Kelimeler

Metotreksat Resveratrol Böbrek toksisitesi dişi sıçanlar

Kaynakça

  • Abdel-Raheem, I.T., Khedr, N.F., 2014. Renoprotective effects of montelukast, a cysteinyl leukotriene receptor antagonist, against methotrexate-induced kidney damage in rats, Naunyn Schmiedebergs Arch. Pharmacol. 387;341–353, http://dx.doi.org/10.1007/s00210-013-0949-x
  • Abouelela, M.E., Orabi, M.A.A., Abdelhamid, R.A., Abdelkader, M.S., Madkor, H.R., Darwish, F.M.M., Hatano, T., Elsadek, B.E.M., 2020. Ethyl acetate extract of Ceiba pentandra (L.) Gaertn. reduces methotrexate-induced renal damage in rats via antioxidant, anti-inflammatory, and antiapoptotic actions. J Tradit Complement Med. 10(5):478-86. https://doi.org/10.1016/j.jtcme.2019.08.006
  • Ahmed, W., Zaki, A.M.R. and Nabil, T., 2015. Prevention of methotrexate-induced nephrotoxicity by concomitantadministration of garlic aqueous extract in rat. Turkish Journal of Medical Sciences. 45(3) 1408-121.
  • Akbel, E., Arslan-Acaroz, D., Demirel, H.H., Kucukkurt, I., Ince, S., 2018. The subchronic exposure to malathion, an organophosphate pesticide, causes lipid peroxidation, oxidative stress, and tissue damage in rats: the protective role of resveratrol, Toxicology Research. 7;3,503–512, https://doi.org/10.1039/c8tx00030a
  • Armagan, I., Bayram, D., Candan, I.A., Yigit, A., Celik, E., Armagan, H.H. et al., 2015. Effects of pentoxifylline and alpha lipoic acid on methotrexate-induced damage in liver and kidney of rats. Environ Toxicol Pharmacol, 39(3);1122-1131
  • Asci, H., Ozmen, O., Ellidag, H.Y., Aydin, B., Bas, E., Yilmaz, N., 2017. The impact of gallic acid on the methotrexate-induced kidney damage in rats. J food drug anal. 25:890–897.
  • Baur, J., Sinclair, D., 2006. Therapeutic potential of resveratrol: the in vivo evidence. Nat Rev Drug Discov 5, 493–506. https://doi.org/10.1038/nrd2060
  • Bay Karabulut A., 2008. Resveratrol and it's effects. Turkiye Klinikleri Journal of Medical Sciences. 28(Suppl):166-169
  • Bedoui, Y., Guillot, X., Sélambarom, J., Guiraud, P., Giry, C., Jaffar-Bandjee, M.C., Ralandison, S., Gasque, P., 2019. Methotrexate an Old Drug with New Tricks. Int. J. Mol. Sci. 20(20):5023. doi: 10.3390/ijms20205023.
  • Baud, L., Ardaillou, R., 1995. Tumor necrosis factor in renal injury. Miner Electrolyte Metab. 21:336–41.
  • Braun, J., Rau, R., 2009. An update on methotrexate. Curr Opin Rheumatol. 21(3):216-23.
  • Brown, V., K. Patel, M. Viskaduraki, et al . 2010. Repeat dose study of the cancer chemopreventive agent resveratrol in healthy volunteers: safety, pharmacokinetics and effect on the insulin-like growth factor axis. Cancer Res. 70: doi. 10.1158/0008-5472.CAN-10-2364.
  • Calamini, B., K. Ratia, M.G. Malkowski, et al . 2010. Pleiotropic mechanisms facilitated by resveratrol and its metabolites. Biochem. J. 429: 273– 282.
  • Chan, E.S.L., Cronstein, B.N., 2013. Mechanisms of action of methotrexate. Bull. NYU Hosp. Jt. Dis. 71:S5–S8
  • Çakır, T., Polat, C., Baştürk, A., Gül, M., Aslaner, A., Durgut, H., Şehirli, A.Ö., Aykaç, A., Bahar, Lç, Sabuncuoglu, M.Z., 2015. The effect of alpha lipoic acid on rat kidneys in methotrexate induced oxidative injury. Eur Rev Med Pharmacol Sci. 19(11):2132-9. PMID: 26125279.
  • Drishya, S., Dhanisha, S. S., & Guruvayoorappan, C., 2022. Antioxidant-rich fraction of Amomum subulatum fruits mitigates experimental methotrexate-induced oxidative stress by regulating TNF-α, IL-1β, and IL-6 proinflammatory cytokines. Journal of Food Biochemistry. 46;e13855. https://doi.org/10.1111/jfbc.13855
  • Elmarakby, A.A. and Sullivan, J.C., 2012. Relationship between Oxidative Stress and Inflammatory Cytokines in Diabetic Nephropathy. Cardiovascular Therapeutics, 30: 49-59. https://doi.org/10.1111/j.1755-5922.2010.00218.x
  • Elmansy, R.A., Seleem, H.S., Mahmoud, A.R., Hassanein, E.H., Ali, F.E., 2021. Rebamipide potentially mitigates methotrexate-induced nephrotoxicity via inhibition of oxidative stress and inflammation: a molecular and histochemical study. Anat Rec. 304:647–661.
  • El-Sheikh, A.A.K., Morsy, M.A. and Al-Taher, A.Y., 2016. Protective mechanisms of resveratrol against methotrexate-induced renal damage may involve BCRP/ABCG2. Fundam Clin Pharmacol, 30: 406-418. https://doi.org/10.1111/fcp.12205
  • El-Sheikh, A.A., Morsy, M.A., Okasha, A.M., 2017. Inhibition of NF-kappaB/TNF-alpha pathway may be involved in the protective effect of resveratrol against cyclophosphamide-induced multi-organ toxicityImmunopharmacol. Immunotoxicol. 39 (4);180-187
  • Erboga, M., Aktas, C., Fidanol Erboga, Z., Bozdemir Donmez, Y. & Gurel, A., 2015. Quercetin ameliorates methotrexate-induced renal damage, apoptosis and oxidative stress in rats, Renal Failure. 37:9, 1492-1497, DOI: 10.3109/0886022X.2015.1074521
  • Fremont, L., 2000. Biological effects of resveratrol.Life Sci.66;663– 673
  • Gaies, E., Jebabli, N., Trabelsi, S., Salouage, I., Charfi, R. et al., 2012. Methotrexate Side Effects: Review Article. J Drug Metab Toxicol 3:125. doi:10.4172/2157-7609.1000125
  • Green, M.R., Chamberlain, M.C., 2009. Renal dysfunction during and after high-dose methotrexate. Cancer Chemother Pharmacol. 63, 599. https://doi.org/10.1007/s00280-008-0772-0
  • Gunyeli, I., Saygin, M. & Ozmen, O.,2021. Methotrexate-induced toxic effects and the ameliorating effects of astaxanthin on genitourinary tissues in a female rat model. Arch Gynecol Obstet 304, 985–997 https://doi.org/10.1007/s00404-021-06000-2
  • Heidari, R., Ahmadi, A., Mohammadi, H., Ommati, M.M., Azarpira, N., Niknahad, H., 2018. Mitochondrial dysfunction and oxidative stress are involved in the mechanism of methotrexate-induced renal injury and electrolytes imbalance, Biomedicine & Pharmacotherapy. 107;834-840.
  • Hobl, E-L., Mader, R.M., Erlacher, L., Duhm, B., Mustak, M., Bröll, H., et al., 2011. The influence of methotrexate on the gene expression of the pro-inflammatory cytokine IL-12A in the therapy of rheumatoid arthritis. Clin Exp Rheumatol. 29:963–969
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Toplam 64 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Konular Sağlık Kurumları Yönetimi
Bölüm Araştırma Makalesi
Yazarlar

Şükriye Yeşilot 0000-0003-3354-8489

Meltem Özgöçmen 0000-0003-3190-4486

Yayımlanma Tarihi 26 Ağustos 2022
Gönderilme Tarihi 28 Haziran 2022
Yayımlandığı Sayı Yıl 2022 Cilt: 10 Sayı: 2

Kaynak Göster

APA Yeşilot, Ş., & Özgöçmen, M. (2022). Nephroprotective effect of Resveratrol against Methotrexate -induced renal toxicity in female rats. Mehmet Akif Ersoy University Journal of Health Sciences Institute, 10(2), 123-133. https://doi.org/10.24998/maeusabed.1136994
AMA Yeşilot Ş, Özgöçmen M. Nephroprotective effect of Resveratrol against Methotrexate -induced renal toxicity in female rats. Mehmet Akif Ersoy University Journal of Health Sciences Institute. Ağustos 2022;10(2):123-133. doi:10.24998/maeusabed.1136994
Chicago Yeşilot, Şükriye, ve Meltem Özgöçmen. “Nephroprotective Effect of Resveratrol Against Methotrexate -Induced Renal Toxicity in Female Rats”. Mehmet Akif Ersoy University Journal of Health Sciences Institute 10, sy. 2 (Ağustos 2022): 123-33. https://doi.org/10.24998/maeusabed.1136994.
EndNote Yeşilot Ş, Özgöçmen M (01 Ağustos 2022) Nephroprotective effect of Resveratrol against Methotrexate -induced renal toxicity in female rats. Mehmet Akif Ersoy University Journal of Health Sciences Institute 10 2 123–133.
IEEE Ş. Yeşilot ve M. Özgöçmen, “Nephroprotective effect of Resveratrol against Methotrexate -induced renal toxicity in female rats”, Mehmet Akif Ersoy University Journal of Health Sciences Institute, c. 10, sy. 2, ss. 123–133, 2022, doi: 10.24998/maeusabed.1136994.
ISNAD Yeşilot, Şükriye - Özgöçmen, Meltem. “Nephroprotective Effect of Resveratrol Against Methotrexate -Induced Renal Toxicity in Female Rats”. Mehmet Akif Ersoy University Journal of Health Sciences Institute 10/2 (Ağustos 2022), 123-133. https://doi.org/10.24998/maeusabed.1136994.
JAMA Yeşilot Ş, Özgöçmen M. Nephroprotective effect of Resveratrol against Methotrexate -induced renal toxicity in female rats. Mehmet Akif Ersoy University Journal of Health Sciences Institute. 2022;10:123–133.
MLA Yeşilot, Şükriye ve Meltem Özgöçmen. “Nephroprotective Effect of Resveratrol Against Methotrexate -Induced Renal Toxicity in Female Rats”. Mehmet Akif Ersoy University Journal of Health Sciences Institute, c. 10, sy. 2, 2022, ss. 123-3, doi:10.24998/maeusabed.1136994.
Vancouver Yeşilot Ş, Özgöçmen M. Nephroprotective effect of Resveratrol against Methotrexate -induced renal toxicity in female rats. Mehmet Akif Ersoy University Journal of Health Sciences Institute. 2022;10(2):123-3.
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