Araştırma Makalesi
BibTex RIS Kaynak Göster

Sıçanlarda Diklofenak ile Oluşturulan Böbrek Toksisitesinde Rutin’in Etkilerinin Histopatolojik ve Biyokimyasal Olarak Araştırılması

Yıl 2025, Cilt: 5 Sayı: 2, 81 - 91, 19.09.2025
https://doi.org/10.62425/jlasp.1581664

Öz

Antiinflamatuar, antipiretik ve analjezik özellikleriyle bilinen nonsteroid antiinflamatuar ilaç (NSAID) kategorisinde yer alan diklofenak (DCL), uzun süreli kullanımı dokularda oksidatif stres ve inflamasyon artışına sebep olarak toksik etki oluşturur. Rutin (RUT), birçok bitkide doğal olarak bulunan anti-oksidan, anti-inflamatuar ve anti-apoptotik etkilere sahip bir flavanoid glikozidtir. Bu çalışmada, doğal bir antioksidan olan RUT’nin DCL kaynaklı böbrek doku hasarı üzerine etkilerinin araştırılması amaçlanmıştır. 28 adet wistar albino cinsi sıçan kontrol, DCL, RUT, DCL50 + RUT100 grupları olmak üzere 4 gruba ayrıldı. 4 gün boyunca 100 mg/kg RUT uygulaması oral yolla verilerek bununla birlikte 3. ve 4. günlerde 50 mg/kg dozda DCL uygulaması intraperitoneal yolla yapıldı. 5. günde böbrek dokuları alındı ve PCR (Polimeraz Zincir Reaksiyonu) yöntemi ile oksidatif stres, inflamasyon ve apoptotik belirteçlerin analizi ve dokuların histopatolojik analizi yapıldı. Böbrek dokularında DCL kaynaklı oksidatif stres, inflamasyon ve apoptoz parametrelerin düzeyleri kontrol grubuna göre artmıştır. RUT uygulamasıyla birlikte DCL bağlı tüm bu artış düzeylerinde azalmalar meydana gelmiştir. Böbrek dokularında DCL maruziyetinin sebep olduğu toksisiteye karşı RUT’nin potansiyel koruyucu etkiye sahip olduğu sonucuna varıldı.

Kaynakça

  • Abiola, Ti.S., Adebayo, O.C. and Babalola, O.O. (2019) Diclofenac-Induced Kidney Damage in Wistar Rats: Involvement of Antioxidant Mechanism. Journal of Biosciences and Medicines, 7, 44-57. https://doi.org/10.4236/jbm.2019.712005
  • Akaras, N., Kandemir, F. M., Şimşek, H., Gür, C., et al. (2023a). Antioxidant, Antiinflammatory, and Antiapoptotic Effects of Rutin in Spleen Toxicity Induced by Sodium Valproate in Rats. Türk Doğa ve Fen Dergisi, 12(2), 138-144. https://doi.org/10.46810/tdfd.1299663
  • Akaras, N., Gur, C., Kucukler, S., & Kandemir, F. M. (2023b). Zingerone reduces sodium arsenite-induced nephrotoxicity by regulating oxidative stress, inflammation, apoptosis and histopathological changes. Chemico-Biological İnteractions, 374, 110410. https://doi.org/10.1016/j.cbi.2023.110410
  • Akaras, N., Ileriturk, M., Gur, C., Kucukler, S., Oz, M., & Kandemir, F. M. (2023c). The protective effects of chrysin on cadmium-induced pulmonary toxicity; a multi-biomarker approach. Environmental Science and Pollution Research İnternational, 30(38), 89479–89494. https://doi.org/10.1007/s11356-023-28747-8
  • Akaras, N., Gür, C., Caglayan, C., & Kandemir, F. M. (2024a). Protective effects of naringin against oxaliplatin-induced testicular damage in rats: Involvement of oxidative stress, inflammation, endoplasmic reticulum stress, apoptosis, and histopathology. Iranian Journal of Basic Medical Sciences, 27(4), 466-474. https://doi.org/10.22038/IJBMS.2024.73824.16048
  • Akaras, N., Kucukler, S., Gur, C., Ileriturk, M., & Kandemir, F. M. (2024b). Sinapic acid protects against lead acetate-induced lung toxicity by reducing oxidative stress, apoptosis, inflammation, and endoplasmic reticulum stress damage. Environmental Toxicology, 39(7), 3820–3832. https://doi.org/10.1002/tox.24255
  • Akarsu, S. A., Gür, C., İleritürk, M., Akaras, N., Küçükler, S., & Kandemir, F. M. (2023). Effect of syringic acid on oxidative stress, autophagy, apoptosis, inflammation pathways against testicular damage induced by lead acetate. Journal of Trace Elements in Medicine and Biology, 80, 127315. https://doi.org/10.1016/j.jtemb.2023.127315
  • Alabi, Q. K., & Akomolafe, R. O. (2020). Kolaviron diminishes diclofenac-induced liver and kidney toxicity in wistar rats via suppressing inflammatory events, upregulating antioxidant defenses, and improving hematological indices. Dose-Response, 18(1), 1559325819899256. https://doi.org/10.1177/1559325819899256
  • Alhoshani, A. R., Hafez, M. M., Husain, S., Al-Sheikh, A. M., Alotaibi, M. R., Al Rejaie, S. S., ... & Al-Shabanah, O. A. (2017). Protective effect of rutin supplementation against cisplatin-induced Nephrotoxicity in rats. BMC Nephrology, 18, 1-10. https://doi.org/10.1186/s12882-017-0601-y
  • Caglayan, C., Kandemir, F. M., Darendelioğlu, E., Yıldırım, S., Kucukler, S., & Dortbudak, M. B. (2019). Rutin ameliorates mercuric chloride-induced hepatotoxicity in rats via interfering with oxidative stress, inflammation and apoptosis. Journal of Trace Elements in Medicine and Biology, 56, 60-68. https://doi.org/10.1016/j.jtemb.2019.07.011
  • Caglayan, C., Kandemir, F. M., Yildirim, S., Kucukler, S., & Eser, G. (2019). Rutin protects mercuric chloride‐induced nephrotoxicity via targeting of aquaporin 1 level, oxidative stress, apoptosis and inflammation in rats. Journal of Trace Elements in Medicine and Biology, 54, 69-78. https://doi.org/10.1016/j.jtemb.2019.04.007
  • Chen, L., Deng, H., Cui, H., Fang, J., Zuo, Z., Deng, J., Li, Y., Wang, X., & Zhao, L. (2017). Inflammatory responses and inflammation-associated diseases in organs. Oncotarget, 9(6), 7204–7218. https://doi.org/10.18632/oncotarget.23208
  • Çomaklı, S., Kandemir, F. M., Küçükler, S., & Özdemir, S. (2022). Morin mitigates ifosfamide induced nephrotoxicity by regulation of NF-kappaB/p53 and Bcl-2 expression. Biotechnic & Histochemistry, 97(6), 423–432. https://doi.org/10.1080/10520295.2021.2021449
  • Çömez, M., Cellat, M., Kuzu, M., Uyar, A., Türk, E., Kaya, Y. S., ... & Güvenç, M. (2024). The effect of tyrosol on diclofenac sodium‐induced acute nephrotoxicity in rats. Journal of Biochemical and Molecular Toxicology, 38(1), e23582. https://doi.org/10.1002/jbt.23582
  • Foufelle, F., & Fromenty, B. (2016). Role of endoplasmic reticulum stress in drug‐induced toxicity. Pharmacology Research & Perspectives, 4(1), e00211. https://doi.org/10.1002/prp2.211
  • Guo, Q., Jin, Y., Chen, X., Ye, X., Shen, X., Lin, M., ... & Zhang, J. (2024). NF-κB in biology and targeted therapy: new insights and translational implications. Signal Transduction and Targeted Therapy, 9(1), 53. https://doi.org/10.1038/s41392-024-01757-9
  • Gür, C., & Kandemir, F. M. (2023). Molecular and biochemical investigation of the protective effects of rutin against liver and kidney toxicity caused by malathion administration in a rat model. Environmental Toxicology, 38(3), 555-565. https://doi.org/10.1002/tox.23700
  • Hickey, E. J., Raje, R. R., Reid, V. E., Gross, S. M., & Ray, S. D. (2001). Diclofenac induced in vivo nephrotoxicity may involve oxidative stress-mediated massive genomic DNA fragmentation and apoptotic cell death. Free Radical Biology and Medicine, 31(2), 139-152. https://doi.org/10.1016/S0891-5849(01)00560-3
  • Kandemir, F. M., Ileriturk, M., & Gur, C. (2022). Rutin protects rat liver and kidney from sodium valproate-induce damage by attenuating oxidative stress, ER stress, inflammation, apoptosis and autophagy. Molecular Biology Reports, 49(7), 6063-6074. https://doi.org/10.1007/s11033-022-07395-0
  • Kandemir, F. M., Caglayan, C., Aksu, E. H., Yildirim, S., Kucukler, S., Gur, C., & Eser, G. (2020). Protective effect of rutin on mercuric chloride‐induced reproductive damage in male rats. Andrologia, 52(3), e13524. https://doi.org/10.1111/and.13524
  • Kandemir, F. M., Ileriturk, M., & Gur, C. (2021). Rutin protects from destruction by ınterrupting the pathways playing a role in the possible damage mechanism of sodium valproate in the liver and kidney tissues of rats. Research Square https://doi.org/10.21203/rs.3.rs-1184419/v1
  • Kankılıç, N. A., Şimşek, H., Akaras, N., Gür, C., İleritürk, M., Küçükler, S., Akarsu, S. A., & Kandemir, F. M. (2024). Protective effects of naringin on colistin-induced damage in rat testicular tissue: Modulating the levels of Nrf-2/HO-1, AKT-2/FOXO1A, Bax/Bcl2/Caspase-3, and Beclin-1/LC3A/LC3B signaling pathways. Journal Of Biochemical and Molecular Toxicology, 38(2), e23643. https://doi.org/10.1002/jbt.23643
  • Karağaç, M. S., Yeşilkent, E. N., Kizir, D., Öztürk, N., Isıyel, M., Karadaş, H., ... & Demir, Y. (2024). Esculetin improves inflammation of the kidney via gene expression against doxorubicin-induced nephrotoxicity in rats: In vivo and in silico studies. Food Bioscience, 62, 105159. https://doi.org/10.1016/j.fbio.2024.105159
  • Keleş, O., Can, S., Cigsar, G., Colak, S., Erol, H., Akaras, N., et al. (2014) Hepatoprotective effects of B-1, 3-(D)- glucan on bortezomib-induced liver damage in rats. Kafkas Universitesi Veteriner Fakultesi Dergisi, 20(6):929-38. https://doi.org/10.9775/kvfd.2014.11413
  • Kim, S. Y., & Moon, A. (2012). Drug-induced nephrotoxicity and its biomarkers. Biomolecules & therapeutics, 20(3), 268.
  • Kwon, T. H., Frøkiær, J., & Nielsen, S. (2013). Regulation of aquaporin-2 in the kidney: A molecular mechanism of body-water homeostasis. Kidney Research and Clinical Practice, 32(3), 96-102. https://doi.org/10.1016/j.krcp.2013.07.005
  • Livak, K. J., & Schmittgen, T. D. (2001). Analysis of Relative Gene Expression Data Using Real‐Time Quantitative PCR and the 2−ΔΔCT Method. Methods, 25(4), (2001): 402–408.
  • Musah, S., Bhattacharya, R., & Himmelfarb, J. (2024). Kidney Disease Modeling with Organoids and Organs-on-Chips. Annual Review of Biomedical Engineering, 26. https://doi.org/10.1146/annurev-bioeng-072623-044010
  • Prince, S. E. (2018). Diclofenac-induced renal toxicity in female Wistar albino rats is protected by the pre-treatment of aqueous leaves extract of Madhuca longifolia through suppression of inflammation, oxidative stress and cytokine formation. Biomedicine & Pharmacotherapy, 98, 45-51. https://doi.org/10.1016/j.biopha.2017.12.028
  • Ricciardi, C. A., & Gnudi, L. (2020). The endoplasmic reticulum stress and the unfolded protein response in kidney disease: Implications for vascular growth factors. Journal of Cellular and Molecular Medicine, 24(22), 12910-12919. https://doi.org/10.1111/jcmm.15999
  • Sirotkin, A. V. (2024). Positive effects of rutin on female reproduction. Reproduction in Domestic Animals, 59(2), e14540. https://doi.org/10.1111/rda.14540
  • Sivaraj, R., & Umarani, S. (2018). Diclofenac-induced biochemical changes in nephrotoxicity among male Albino rats. Int J Basic Clin Pharmacol, 7(4), 640-643. https://doi.org/10.18203/2319-2003.ijbcp20181162
  • Şimşek, H., Akaras, N., Gür, C., Küçükler, S., & Kandemir, F. M. (2023). Beneficial effects of Chrysin on Cadmium‐induced nephrotoxicity in rats: Modulating the levels of Nrf2/HO‐1, RAGE/NLRP3, and Caspase-3/Bax/Bcl-2 signaling pathways. Gene, 875, 147502. https://doi.org/10.1016/j.gene.2023.147502
  • Tanyeli, A., Eraslan, E., GÜLER, M., Kurt, N., & Akaras, N. (2020). Gossypin protects against renal ischemia-reperfusion injury in rats. Kafkas Universitesi Veteriner Fakultesi Dergisi, 26(1). https://doi.org/10.9775/kvfd.2019.22396
  • Taştan Bal, T., Akaras, N., Demir, Ö., & Ugan, R. A. (2023). Protective effect of astaxanthin and metformin in the liver of rats in which the polycystic ovary syndrome model was formed by giving letrozole. Iranian Journal of Basic Medical Sciences, 26(6), 688–694. https://doi.org/10.22038/IJBMS.2023.68032.14872
  • Thai, P. N., Ren, L., Xu, W., Overton, J., Timofeyev, V., Nader, C. E., Haddad, M., Yang, J., Gomes, A. V., Hammock, B. D., Chiamvimonvat, N., & Sirish, P. (2023). Chronic Diclofenac Exposure Increases Mitochondrial Oxidative Stress, Inflammatory Mediators, and Cardiac Dysfunction. Cardiovascular Drugs and Therapy, 37(1), 25–37. https://doi.org/10.1007/s10557-021-07253-4
  • Uehara, Y., Murata, Y., Shiga, S., & Hosoi, Y. (2016). NSAIDs diclofenac, indomethacin, and meloxicam highly upregulate expression of ICAM-1 and COX-2 induced by X-irradiation in human endothelial cells. Biochemical and Biophysical Research Communications, 479(4), 847-852. https://doi.org/10.1016/j.bbrc.2016.09.120
  • Varışlı, B., Caglayan, C., Kandemir, F. M., Gür, C., Ayna, A., Genç, A., & Taysı, S. (2023). Chrysin mitigates diclofenac-induced hepatotoxicity by modulating oxidative stress, apoptosis, autophagy and endoplasmic reticulum stress in rats. Molecular Biology Reports, 50(1), 433-442. https://doi.org/10.1007/s11033-022-07928-7
  • Wadie, W., Abdel-Razek, N. S., & Salem, H. A. (2021). Phosphodiesterase (1, 3 & 5) inhibitors attenuate diclofenac-induced acute kidney toxicity in rats. Life Sciences, 277, 119506. https://doi.org/10.1016/j.lfs.2021.119506
  • Wang, L., Sun, W., Ma, X., Griffin, N., & Liu, H. (2024). Perfluorooctanoic acid (PFOA) exposure induces renal filtration and reabsorption disorders via down-regulation of aquaporins. Toxicology Letters, 392, 22-35. https://doi.org/10.1016/j.toxlet.2023.12.003
  • Yuan, S., She, D., Jiang, S., Deng, N., Peng, J., & Ma, L. (2024). Endoplasmic reticulum stress and therapeutic strategies in metabolic, neurodegenerative diseases and cancer. Molecular Medicine, 30(1), 40. https://doi.org/10.1186/s10020-024-00808-9

Histopathological and Biochemical Investigation of the Effects of Rutin on Diclofenac-Induced Renal Toxicity in Rats

Yıl 2025, Cilt: 5 Sayı: 2, 81 - 91, 19.09.2025
https://doi.org/10.62425/jlasp.1581664

Öz

Diclofenac (DCL), known for its anti-inflammatory, antipyretic, and analgesic properties, belongs to the category of nonsteroidal anti-inflammatory drugs (NSAIDs) and can cause toxic effects due to increased oxidative stress and inflammation in tissues with long-term use. Rutin (RUT) is a flavonoid glycoside that naturally occurs in many plants and possesses antioxidant, anti-inflammatory, and anti-apoptotic effects. This study aimed to investigate the effects of RUT, a natural antioxidant, on DCL-induced kidney tissue damage. A total of 28 Wistar albino rats were divided into 4 groups: control, DCL, RUT, and DCL50 + RUT100. For 4 days, 100 mg/kg of RUT was administered orally, and on the 3rd and 4th days, 50 mg/kg of DCL was administered intraperitoneally. On the 5th day, kidney tissues were collected, and the analysis of oxidative stress, inflammation, and apoptotic markers was performed using the PCR (Polymerase Chain Reaction) method, along with histopathological analysis of the tissues. The levels of oxidative stress, inflammation, and apoptosis parameters in kidney tissues were found to be increased in the DCL group compared to the control group. The administration of RUT resulted in reductions in all these elevated levels associated with DCL. It was concluded that RUT has a potential protective effect against the toxicity caused by DCL exposure in kidney tissues.

Kaynakça

  • Abiola, Ti.S., Adebayo, O.C. and Babalola, O.O. (2019) Diclofenac-Induced Kidney Damage in Wistar Rats: Involvement of Antioxidant Mechanism. Journal of Biosciences and Medicines, 7, 44-57. https://doi.org/10.4236/jbm.2019.712005
  • Akaras, N., Kandemir, F. M., Şimşek, H., Gür, C., et al. (2023a). Antioxidant, Antiinflammatory, and Antiapoptotic Effects of Rutin in Spleen Toxicity Induced by Sodium Valproate in Rats. Türk Doğa ve Fen Dergisi, 12(2), 138-144. https://doi.org/10.46810/tdfd.1299663
  • Akaras, N., Gur, C., Kucukler, S., & Kandemir, F. M. (2023b). Zingerone reduces sodium arsenite-induced nephrotoxicity by regulating oxidative stress, inflammation, apoptosis and histopathological changes. Chemico-Biological İnteractions, 374, 110410. https://doi.org/10.1016/j.cbi.2023.110410
  • Akaras, N., Ileriturk, M., Gur, C., Kucukler, S., Oz, M., & Kandemir, F. M. (2023c). The protective effects of chrysin on cadmium-induced pulmonary toxicity; a multi-biomarker approach. Environmental Science and Pollution Research İnternational, 30(38), 89479–89494. https://doi.org/10.1007/s11356-023-28747-8
  • Akaras, N., Gür, C., Caglayan, C., & Kandemir, F. M. (2024a). Protective effects of naringin against oxaliplatin-induced testicular damage in rats: Involvement of oxidative stress, inflammation, endoplasmic reticulum stress, apoptosis, and histopathology. Iranian Journal of Basic Medical Sciences, 27(4), 466-474. https://doi.org/10.22038/IJBMS.2024.73824.16048
  • Akaras, N., Kucukler, S., Gur, C., Ileriturk, M., & Kandemir, F. M. (2024b). Sinapic acid protects against lead acetate-induced lung toxicity by reducing oxidative stress, apoptosis, inflammation, and endoplasmic reticulum stress damage. Environmental Toxicology, 39(7), 3820–3832. https://doi.org/10.1002/tox.24255
  • Akarsu, S. A., Gür, C., İleritürk, M., Akaras, N., Küçükler, S., & Kandemir, F. M. (2023). Effect of syringic acid on oxidative stress, autophagy, apoptosis, inflammation pathways against testicular damage induced by lead acetate. Journal of Trace Elements in Medicine and Biology, 80, 127315. https://doi.org/10.1016/j.jtemb.2023.127315
  • Alabi, Q. K., & Akomolafe, R. O. (2020). Kolaviron diminishes diclofenac-induced liver and kidney toxicity in wistar rats via suppressing inflammatory events, upregulating antioxidant defenses, and improving hematological indices. Dose-Response, 18(1), 1559325819899256. https://doi.org/10.1177/1559325819899256
  • Alhoshani, A. R., Hafez, M. M., Husain, S., Al-Sheikh, A. M., Alotaibi, M. R., Al Rejaie, S. S., ... & Al-Shabanah, O. A. (2017). Protective effect of rutin supplementation against cisplatin-induced Nephrotoxicity in rats. BMC Nephrology, 18, 1-10. https://doi.org/10.1186/s12882-017-0601-y
  • Caglayan, C., Kandemir, F. M., Darendelioğlu, E., Yıldırım, S., Kucukler, S., & Dortbudak, M. B. (2019). Rutin ameliorates mercuric chloride-induced hepatotoxicity in rats via interfering with oxidative stress, inflammation and apoptosis. Journal of Trace Elements in Medicine and Biology, 56, 60-68. https://doi.org/10.1016/j.jtemb.2019.07.011
  • Caglayan, C., Kandemir, F. M., Yildirim, S., Kucukler, S., & Eser, G. (2019). Rutin protects mercuric chloride‐induced nephrotoxicity via targeting of aquaporin 1 level, oxidative stress, apoptosis and inflammation in rats. Journal of Trace Elements in Medicine and Biology, 54, 69-78. https://doi.org/10.1016/j.jtemb.2019.04.007
  • Chen, L., Deng, H., Cui, H., Fang, J., Zuo, Z., Deng, J., Li, Y., Wang, X., & Zhao, L. (2017). Inflammatory responses and inflammation-associated diseases in organs. Oncotarget, 9(6), 7204–7218. https://doi.org/10.18632/oncotarget.23208
  • Çomaklı, S., Kandemir, F. M., Küçükler, S., & Özdemir, S. (2022). Morin mitigates ifosfamide induced nephrotoxicity by regulation of NF-kappaB/p53 and Bcl-2 expression. Biotechnic & Histochemistry, 97(6), 423–432. https://doi.org/10.1080/10520295.2021.2021449
  • Çömez, M., Cellat, M., Kuzu, M., Uyar, A., Türk, E., Kaya, Y. S., ... & Güvenç, M. (2024). The effect of tyrosol on diclofenac sodium‐induced acute nephrotoxicity in rats. Journal of Biochemical and Molecular Toxicology, 38(1), e23582. https://doi.org/10.1002/jbt.23582
  • Foufelle, F., & Fromenty, B. (2016). Role of endoplasmic reticulum stress in drug‐induced toxicity. Pharmacology Research & Perspectives, 4(1), e00211. https://doi.org/10.1002/prp2.211
  • Guo, Q., Jin, Y., Chen, X., Ye, X., Shen, X., Lin, M., ... & Zhang, J. (2024). NF-κB in biology and targeted therapy: new insights and translational implications. Signal Transduction and Targeted Therapy, 9(1), 53. https://doi.org/10.1038/s41392-024-01757-9
  • Gür, C., & Kandemir, F. M. (2023). Molecular and biochemical investigation of the protective effects of rutin against liver and kidney toxicity caused by malathion administration in a rat model. Environmental Toxicology, 38(3), 555-565. https://doi.org/10.1002/tox.23700
  • Hickey, E. J., Raje, R. R., Reid, V. E., Gross, S. M., & Ray, S. D. (2001). Diclofenac induced in vivo nephrotoxicity may involve oxidative stress-mediated massive genomic DNA fragmentation and apoptotic cell death. Free Radical Biology and Medicine, 31(2), 139-152. https://doi.org/10.1016/S0891-5849(01)00560-3
  • Kandemir, F. M., Ileriturk, M., & Gur, C. (2022). Rutin protects rat liver and kidney from sodium valproate-induce damage by attenuating oxidative stress, ER stress, inflammation, apoptosis and autophagy. Molecular Biology Reports, 49(7), 6063-6074. https://doi.org/10.1007/s11033-022-07395-0
  • Kandemir, F. M., Caglayan, C., Aksu, E. H., Yildirim, S., Kucukler, S., Gur, C., & Eser, G. (2020). Protective effect of rutin on mercuric chloride‐induced reproductive damage in male rats. Andrologia, 52(3), e13524. https://doi.org/10.1111/and.13524
  • Kandemir, F. M., Ileriturk, M., & Gur, C. (2021). Rutin protects from destruction by ınterrupting the pathways playing a role in the possible damage mechanism of sodium valproate in the liver and kidney tissues of rats. Research Square https://doi.org/10.21203/rs.3.rs-1184419/v1
  • Kankılıç, N. A., Şimşek, H., Akaras, N., Gür, C., İleritürk, M., Küçükler, S., Akarsu, S. A., & Kandemir, F. M. (2024). Protective effects of naringin on colistin-induced damage in rat testicular tissue: Modulating the levels of Nrf-2/HO-1, AKT-2/FOXO1A, Bax/Bcl2/Caspase-3, and Beclin-1/LC3A/LC3B signaling pathways. Journal Of Biochemical and Molecular Toxicology, 38(2), e23643. https://doi.org/10.1002/jbt.23643
  • Karağaç, M. S., Yeşilkent, E. N., Kizir, D., Öztürk, N., Isıyel, M., Karadaş, H., ... & Demir, Y. (2024). Esculetin improves inflammation of the kidney via gene expression against doxorubicin-induced nephrotoxicity in rats: In vivo and in silico studies. Food Bioscience, 62, 105159. https://doi.org/10.1016/j.fbio.2024.105159
  • Keleş, O., Can, S., Cigsar, G., Colak, S., Erol, H., Akaras, N., et al. (2014) Hepatoprotective effects of B-1, 3-(D)- glucan on bortezomib-induced liver damage in rats. Kafkas Universitesi Veteriner Fakultesi Dergisi, 20(6):929-38. https://doi.org/10.9775/kvfd.2014.11413
  • Kim, S. Y., & Moon, A. (2012). Drug-induced nephrotoxicity and its biomarkers. Biomolecules & therapeutics, 20(3), 268.
  • Kwon, T. H., Frøkiær, J., & Nielsen, S. (2013). Regulation of aquaporin-2 in the kidney: A molecular mechanism of body-water homeostasis. Kidney Research and Clinical Practice, 32(3), 96-102. https://doi.org/10.1016/j.krcp.2013.07.005
  • Livak, K. J., & Schmittgen, T. D. (2001). Analysis of Relative Gene Expression Data Using Real‐Time Quantitative PCR and the 2−ΔΔCT Method. Methods, 25(4), (2001): 402–408.
  • Musah, S., Bhattacharya, R., & Himmelfarb, J. (2024). Kidney Disease Modeling with Organoids and Organs-on-Chips. Annual Review of Biomedical Engineering, 26. https://doi.org/10.1146/annurev-bioeng-072623-044010
  • Prince, S. E. (2018). Diclofenac-induced renal toxicity in female Wistar albino rats is protected by the pre-treatment of aqueous leaves extract of Madhuca longifolia through suppression of inflammation, oxidative stress and cytokine formation. Biomedicine & Pharmacotherapy, 98, 45-51. https://doi.org/10.1016/j.biopha.2017.12.028
  • Ricciardi, C. A., & Gnudi, L. (2020). The endoplasmic reticulum stress and the unfolded protein response in kidney disease: Implications for vascular growth factors. Journal of Cellular and Molecular Medicine, 24(22), 12910-12919. https://doi.org/10.1111/jcmm.15999
  • Sirotkin, A. V. (2024). Positive effects of rutin on female reproduction. Reproduction in Domestic Animals, 59(2), e14540. https://doi.org/10.1111/rda.14540
  • Sivaraj, R., & Umarani, S. (2018). Diclofenac-induced biochemical changes in nephrotoxicity among male Albino rats. Int J Basic Clin Pharmacol, 7(4), 640-643. https://doi.org/10.18203/2319-2003.ijbcp20181162
  • Şimşek, H., Akaras, N., Gür, C., Küçükler, S., & Kandemir, F. M. (2023). Beneficial effects of Chrysin on Cadmium‐induced nephrotoxicity in rats: Modulating the levels of Nrf2/HO‐1, RAGE/NLRP3, and Caspase-3/Bax/Bcl-2 signaling pathways. Gene, 875, 147502. https://doi.org/10.1016/j.gene.2023.147502
  • Tanyeli, A., Eraslan, E., GÜLER, M., Kurt, N., & Akaras, N. (2020). Gossypin protects against renal ischemia-reperfusion injury in rats. Kafkas Universitesi Veteriner Fakultesi Dergisi, 26(1). https://doi.org/10.9775/kvfd.2019.22396
  • Taştan Bal, T., Akaras, N., Demir, Ö., & Ugan, R. A. (2023). Protective effect of astaxanthin and metformin in the liver of rats in which the polycystic ovary syndrome model was formed by giving letrozole. Iranian Journal of Basic Medical Sciences, 26(6), 688–694. https://doi.org/10.22038/IJBMS.2023.68032.14872
  • Thai, P. N., Ren, L., Xu, W., Overton, J., Timofeyev, V., Nader, C. E., Haddad, M., Yang, J., Gomes, A. V., Hammock, B. D., Chiamvimonvat, N., & Sirish, P. (2023). Chronic Diclofenac Exposure Increases Mitochondrial Oxidative Stress, Inflammatory Mediators, and Cardiac Dysfunction. Cardiovascular Drugs and Therapy, 37(1), 25–37. https://doi.org/10.1007/s10557-021-07253-4
  • Uehara, Y., Murata, Y., Shiga, S., & Hosoi, Y. (2016). NSAIDs diclofenac, indomethacin, and meloxicam highly upregulate expression of ICAM-1 and COX-2 induced by X-irradiation in human endothelial cells. Biochemical and Biophysical Research Communications, 479(4), 847-852. https://doi.org/10.1016/j.bbrc.2016.09.120
  • Varışlı, B., Caglayan, C., Kandemir, F. M., Gür, C., Ayna, A., Genç, A., & Taysı, S. (2023). Chrysin mitigates diclofenac-induced hepatotoxicity by modulating oxidative stress, apoptosis, autophagy and endoplasmic reticulum stress in rats. Molecular Biology Reports, 50(1), 433-442. https://doi.org/10.1007/s11033-022-07928-7
  • Wadie, W., Abdel-Razek, N. S., & Salem, H. A. (2021). Phosphodiesterase (1, 3 & 5) inhibitors attenuate diclofenac-induced acute kidney toxicity in rats. Life Sciences, 277, 119506. https://doi.org/10.1016/j.lfs.2021.119506
  • Wang, L., Sun, W., Ma, X., Griffin, N., & Liu, H. (2024). Perfluorooctanoic acid (PFOA) exposure induces renal filtration and reabsorption disorders via down-regulation of aquaporins. Toxicology Letters, 392, 22-35. https://doi.org/10.1016/j.toxlet.2023.12.003
  • Yuan, S., She, D., Jiang, S., Deng, N., Peng, J., & Ma, L. (2024). Endoplasmic reticulum stress and therapeutic strategies in metabolic, neurodegenerative diseases and cancer. Molecular Medicine, 30(1), 40. https://doi.org/10.1186/s10020-024-00808-9
Toplam 41 adet kaynakça vardır.

Ayrıntılar

Birincil Dil Türkçe
Konular Biyokimya ve Hücre Biyolojisi (Diğer)
Bölüm Araştırma Makaleleri
Yazarlar

Rabia Oğuz Kabayel 0000-0003-2992-3880

Nurhan Akaras 0000-0002-8457-9448

Özge Kandemir 0000-0001-8884-4168

Hasan Şimşek 0000-0001-5573-4923

Fatih Mehmet Kandemir 0000-0002-8490-2479

Yayımlanma Tarihi 19 Eylül 2025
Gönderilme Tarihi 8 Kasım 2024
Kabul Tarihi 25 Nisan 2025
Yayımlandığı Sayı Yıl 2025 Cilt: 5 Sayı: 2

Kaynak Göster

EndNote Oğuz Kabayel R, Akaras N, Kandemir Ö, Şimşek H, Kandemir FM (01 Eylül 2025) Sıçanlarda Diklofenak ile Oluşturulan Böbrek Toksisitesinde Rutin’in Etkilerinin Histopatolojik ve Biyokimyasal Olarak Araştırılması. Laboratuvar Hayvanları Bilimi ve Uygulamaları Dergisi 5 2 81–91.

Content of this journal is licensed under a Creative Commons Attribution NonCommercial 4.0 International License

29929