KaydedilenlerDerginizi ekleyin

Dergiler / Kocatepe Veteriner Dergisi / 2024 / Cilt: 17 Sayı: 4

Ratlarda Sodyum Valproat Kaynaklı Akciğer Hasarı Üzerine Rutin’in Etkilerinin Araştırılması

Investigation of the Effects of Rutin on Sodium Valproate-Induced Lung Damage in Rats

Özge Kandemir(AKSARAY ÜNİVERSİTESİ, AKSARAY TEKNİK BİLİMLER MESLEK YÜKSEKOKULU)0000-0001-8884-4168
Cihan Gür(ATATURK UNIVERSITY)0000-0001-6775-7858
Sayfa
315–324
Yayın Tarihi
2025-01-03
🏛️Bu makalenin bibliyografik verileri ve tam metin bağlantısı DergiPark üzerinden sağlanmıştır.
DergiPark Kaydı ↗
✨

Yapay Zeka Hızlı Bakış & Çıkarımlar

AI Insight
⚡ TL;DR(1 Cümlede Hızlı Çıkarım)

Tedavi edici özelliği yanı sıra yüksek doz ve uzun süre alımlarda çoğu organda toksik etki göstermektedir.

📌 3 Maddede Bu Makale

🎯
Amaç & Hipotez:Sodium valproat (SVP), başta epilepsi olmak üzere migren ve bipolar bozukluklarda yaygın kullanılan bir ilaçtır.
📊
Temel Bulgular & Veri:Tedavi edici özelliği yanı sıra yüksek doz ve uzun süre alımlarda çoğu organda toksik etki göstermektedir.
💡
Sonuç & Katkı:Sonuç olarak SVP kaynaklı akciğer hasarına karşı rutin kullanımının faydalı olduğu belirlendi.
🔬Tür:Deneysel Tarla Denemesi
📍Kapsam:Genişletilmiş Akademik Örneklem
⚙️Değişkenler:Akciğer hasarı · Rat · Rutin

Özet

Sodium valproat (SVP), başta epilepsi olmak üzere migren ve bipolar bozukluklarda yaygın kullanılan bir ilaçtır. Tedavi edici özelliği yanı sıra yüksek doz ve uzun süre alımlarda çoğu organda toksik etki göstermektedir. Rutin flavanoit türevi doğal bir antioksidandır ve birçok toksikasyonda başarı ile kullanılmıştır. Sunulan çalışmada SVP kaynaklı akciğer hasarı üzerine rutin’ in etkilerinin araştırılması amaçlanmıştır. Çalışmada 35 Sprague Dawley rat kontrol, Rutin, SVP, SVP+Rutin 50 ve SVP+Rutin 100 olmak üzere beş eşit gruba ayrılarak 14 gün oral yolla uygulamalar devam etmiştir. Çalışma sonunda akciğer dokusu alınarak oksidatif stres (MDA, GSH, SOD, CAT, GPx, Nrf-2, HO-1), endoplazmik retikulum stresi (ATF-6, PERK), inflamasyon (NF-ĸB, TNF-α), apoptoz (Bax, Bcl-2, Caspase-3) ve otofaji (Beclin-1) parametreleri incelenmiştir. Elde edilen veriler SVP’ nin antioksidan enzim aktivitelerini azaltarak savunma sistemini zayıflattığını, lipid peroksidasyonu, inflamasyonu, apoptozisi ve otofajiyi artırarak hücrede hasarın artmasına neden olduğu göstermiştir. SVP ile birlikte rutin 50 ve rutin 100 dozlarının antioksidan savunma sistemini güçlendirdiği, lipid peroksidasyonunu, endoplasmik retikulum stresini, inflamasyonu, apoptoz ve otofajiyi baskılayarak hücreyi hasardan korumada etkili olduğu tespit edildi. Sonuç olarak SVP kaynaklı akciğer hasarına karşı rutin kullanımının faydalı olduğu belirlendi.

Abstract

Sodium valproate (SVP) is a drug widely used in epilepsy, migraine, and bipolar disorders. In addition to its therapeutic properties, it has toxic effects on many organs in high doses and prolonged intake. Rutin flavonoid derivative is a natural antioxidant and has been successfully used in many toxications. In the present study, it was aimed to investigate the effects of rutin on SVP-induced lung injury. In the study, 35 Sprague Dawley rats were divided into five equal groups as control, routine, SVP, SVP+Rutin 50 and SVP+Rutin 100 and oral administration was continued for 14 days. At the end of the study, lung tissue was obtained and oxidative stress (MDA, GSH, SOD, CAT, GPx, Nrf-2, HO-1), endoplasmic reticulum stress (ATF-6, PERK), inflammation (NF-ĸB, TNF-α), apoptosis (Bax, Bcl-2, Caspase-3) and autophagy (Beclin-1) parameters were analyzed. The data obtained showed that SVP weakened the defense system by decreasing antioxidant enzyme activities and increased lipid peroxidation, inflammation, apoptosis, and autophagy, leading to increased cell damage. It was determined that SVP and rutin 50 and rutin 100 doses strengthened the antioxidant defense system, suppressed lipid peroxidation, endoplasmic reticulum stress, inflammation, apoptosis, and autophagy, and were effective in protecting the cell from damage. As a result, it was determined that rutin use was beneficial against SVP-induced lung injury.

🔖

Bu Makaleye Atıf Yap

Kandemir, Ö., Gür, C. (2025). Ratlarda Sodyum Valproat Kaynaklı Akciğer Hasarı Üzerine Rutin’in Etkilerinin Araştırılması. Kocatepe Veteriner Dergisi, Cilt: 17 Sayı: 4, 315–324. https://doi.org/10.30607/kvj.1522115

📄 Tam Metin PDF Okuyucu

📄

PDF görüntüleyici hazırlanıyor...

Kaynakça (62)

  1. Aebi, H. (1984). Catalase in vitro. In Methods in Enzymology (Vol. 105, pp. 121-126). Academic press.
  2. Abu-Risha, S. E., Sokar, S. S., Elzorkany, K. E., & Elsisi, A. E. (2024). Donepezil and quercetin alleviate valproate-induced testicular oxidative stress, inflammation and apoptosis: Imperative roles of AMPK/SIRT1/PGC-1α and p38-MAPK/NF-κB/IL-1β signaling cascades. Int. Immunopharmacol,, 134, 112240. https://doi.org/10.1016/j.intimp.2024.112240
  3. Akaras, N., Kandemir, F. M., Şimşek, H., Gür, C., & Aygörmez, S. (2023a). Antioxidant, Antiinflammatory, and Antiapoptotic Effects of Rutin in Spleen Toxicity Induced by Sodium Valproate in Rats. Tr. J. Nature Sci., 12(2), 138-144. https://doi.org/10.46810/tdfd.1299663
  4. Akaras, N., Ileriturk, M., Gur, C., Kucukler, S., Oz, M., & Kandemir, F. M. (2023b). The protective effects of chrysin on cadmium-induced pulmonary toxicity; a multi-biomarker approach. Environ. Sci. Pollut. Res., 30(38), 89479-89494. https://doi.org/10.1007/s11356-023-28747-8
  5. Akarsu, S. A., Kankılıç, N. A., & Erdoğan, E. (2023a). Investigation of the Effects of Rutin on Valproic Acid Induced Testicular Damage in Rats. Kocatepe Vet. J., 16(3), 260-268. https://doi.org/10.30607/kvj.1295945
  6. Akarsu, S. A., Gür, C., İleritürk, M., Akaras, N., Küçükler, S., & Kandemir, F. M. (2023b). Effect of syringic acid on oxidative stress, autophagy, apoptosis, inflammation pathways against testicular damage induced by lead acetate. J. Trace Elem. Med. Biol., 80, 127315. https://doi.org/10.1016/j.jtemb.2023.127315
  7. Aksu, E. H., Kandemir, F. M., Küçükler, S., & Mahamadu, A. (2018). Improvement in colistin‐induced reproductive damage, apoptosis, and autophagy in testes via reducing oxidative stress by chrysin. Journal of biochemical and molecular toxicology, 32(11), e22201. https://doi.org/10.1002/jbt.22201
  8. Akcılar, R., Akcılar, A., Şimşek, H., Koçak, F. E., Koçak, C., Yümün, G., & Bayat, Z. (2015a). Hyperbaric oxygen treatment ameliorates lung injury in paraquat intoxicated rats. International Journal of Clinical and Experimental Pathology, 8(10), 13034.
  9. Akcılar, R., Akcılar, A., Koçak, C., Koçak, F. E., Bayat, Z., Şimşek, H.,. & Savran, B. (2015b). Effects of Ukrain on intestinal apoptosis caused by ischemia-reperfusion injury in rats. International Journal of Clinical and Experimental Medicine, 8(12), 22158.
  10. Al-Rafiah, A. R., & Mehdar, K. M. (2021). Histopathological and biochemical assessment of neuroprotective effects of sodium valproate and lutein on the pilocarpine albino rat model of epilepsy. Behav. Neurol., 2021(1), 5549638. https://doi.org/10.1155/2021/5549638
  11. Aydin, M., Cevik, A., Kandemir, F. M., Yuksel, M., & Apaydin, A. M. (2009). Evaluation of hormonal change, biochemical parameters, and histopathological status of uterus in rats exposed to 50-Hz electromagnetic field. Toxicol. Ind. Health, 25(3), 153-158. 10.1177/0748233709102717
  12. Chaudhary, S., Ganjoo, P., Raiusddin, S., & Parvez, S. (2015). Nephroprotective activities of quercetin with potential relevance to oxidative stress induced by valproic acid. Protoplasma, 252, 209-217. https://doi.org/10.1007/s00709-014-0670-8
  13. Chen, B., Wang, J. F., & Young, L. T. (2000). Chronic valproate treatment increases expression of endoplasmic reticulum stress proteins in the rat cerebral cortex and hippocampus. Biol. Psychiatry, 48(7), 658-664. https://doi.org/10.1016/S0006-3223(00)00878-7
  14. Çomaklı, S., Özdemir, S., Küçükler, S., & Kandemir, F. M. (2023). Beneficial effects of quercetin on vincristine‐induced liver injury in rats: Modulating the levels of Nrf2/HO‐1, NF‐kB/STAT3, and SIRT1/PGC‐1α. J. Biochem. Mol. Toxicol, 37(5), e23326. https://doi.org/10.1002/jbt.23326
  15. Ekinci Akdemir, F. N., Yildirim, S., Kandemir, F. M., Aksu, E. H., Guler, M. C., Kiziltunc Ozmen, H.,. & Eser, G. (2019). The antiapoptotic and antioxidant effects of eugenol against cisplatin‐induced testicular damage in the experimental model. Andrologia, 51(9), e13353. https://doi.org/10.1111/and.13353
  16. Ekinci Akdemir, F. N., Yıldırım, S., & Kandemir, F. M. (2022). The possible beneficial impacts of evodiamine on hepatotoxicity induced by cisplatin. Environ. Sci. Pollut. Res., 29(59), 89522-89529. https://doi.org/10.1007/s11356-022-22007-x
  17. Genc, M., Kandemir, F. M., & Coban, O. (2019). Effects of in-ovo rutin injection to fertile Japanese quail (Coturnix Coturnix Japonica) egg on hatchability, embryonic death, hatchling weight, and hatchling liver oxidative and nitrosative stress. Braz. J. Poultry Sci., 21(01), eRBCA-2019. https://doi.org/10.1590/1806-9061-2018-0786
  18. Gheena, S., Ezhilarasan, D., Shree Harini, K., & Rajeshkumar, S. (2022). Syringic acid and silymarin concurrent administration inhibits sodium valproate‐induced liver injury in rats. Environ. Toxicol., 37(9), 2143-2152. https://doi.org/10.1002/tox.23557
  19. Gur, C., Kandemir, F. M., Caglayan, C., & Satıcı, E. (2022). Chemopreventive effects of hesperidin against paclitaxel-induced hepatotoxicity and nephrotoxicity via amendment of Nrf2/HO-1 and caspase-3/Bax/Bcl-2 signaling pathways. Chem. Biol. Interact., 365, 110073. https://doi.org/10.1016/j.cbi.2022.110073
  20. Gur, 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. Environ. Toxicol., 38(3), 555-565. https://doi.org/10.1002/tox.23700
  21. Gur, C., Akarsu, S. A., Akaras, N., Tuncer, S. C., & Kandemir, F. M. (2023). Carvacrol reduces abnormal and dead sperm counts by attenuating sodium arsenite‐induced oxidative stress, inflammation, apoptosis, and autophagy in the testicular tissues of rats. Environ. Toxicol., 38(6), 1265-1276. https://doi.org/10.1002/tox.23762
  22. Ileriturk, M., Ileriturk, D., Kandemir, O., Akaras, N., Simsek, H., Erdogan, E., & Kandemir, F. M. (2024). Naringin attenuates oxaliplatin‐induced nephrotoxicity and hepatotoxicity: A molecular, biochemical, and histopathological approach in a rat model. Journal of Biochemical and Molecular Toxicology, 38(1), e23604.
  23. 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. Mol. Biol. Rep., 49(7), 6063-6074. https://doi.org/10.1007/s11033-022-07395-0
  24. Kandemir, F. M., Caglayan, C., Darendelioğlu, E., Küçükler, S., İzol, E., & Kandemir, Ö. (2021). Modulatory effects of carvacrol against cadmium-induced hepatotoxicity and nephrotoxicity by molecular targeting regulation. Life Sci., 277, 119610. https://doi.org/10.1016/j.lfs.2021.119610
  25. Kandemir, F. M., Ozkaraca, M., Küçükler, S., Caglayan, C., & Hanedan, B. (2018). Preventive effects of hesperidin on diabetic nephropathy induced by streptozotocin via modulating TGF-β1 and oxidative DNA damage. Toxin Rev., 37(4), 287-293. https://doi.org/10.1080/15569543.2017.1364268
  26. Kankılıç, N. A., Şimşek, H., Akaras, N., Gür, C., İleritürk, M., Küçükler, S.,. & Kandemir, F. M. (2024a). 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. J. Biochem. Mol. Toxicol., 38(2), e23643. https://doi.org/10.1002/jbt.23643
  27. Kankılıç, N. A., Küçükler, S., Gür, C., Akarsu, S. A., Akaras, N., Şimşek, H.,. & Kandemir, F. M. (2024c). Naringin protects against paclitaxel‐induced toxicity in rat testicular tissues by regulating genes in pro‐inflammatory cytokines, oxidative stress, apoptosis, and JNK/MAPK signaling pathways. J. Biochem. Mol. Toxicol, 38(7), e23751. https://doi.org/10.1002/jbt.23751
  28. Kankılıç, N. A., Şimşek, H., Akaras, N., Gür, C., Küçükler, S., İleritürk, M.,. & Kandemir, F. M. (2024). The ameliorative effects of chrysin on bortezomib-induced nephrotoxicity in rats: reduces oxidative stress, endoplasmic reticulum stress, inflammation damage, apoptotic and autophagic death. Food Chem. Toxicol., 114791. https://doi.org/10.1016/j.fct.2024.114791
  29. Keleş, O.N., Can, S., Çığşar, S., Çolak, S., Erol, H.S., Akaras, N., Erdemci, B., Bilgin, B.Ç., Can, İ., Ünal, B., Halıcı, M.B. (2014). Bortezomib-Induced Liver Damage in Rats. Kafkas Vet. Fak. Derg. 20(6):929-938. https://doi.org/10.9775/kvfd.2014.11413
  30. Kocak, C., Kocak, F. E., Akcilar, R., Isiklar, O. O., Kocak, H., Bayat, Z.,. & Altuntas, I. (2016). Molecular and biochemical evidence on the protective effects of embelin and carnosic acid in isoproterenol-induced acute myocardial injury in rats. Life sciences, 147, 15-23. https://doi.org/10.1016/j.lfs.2016.01.038
  31. Koroglu, O. F., Gunata, M., Vardi, N., Yildiz, A., Ates, B., Colak, C.,. & Parlakpinar, H. (2021). Protective effects of naringin on valproic acid-induced hepatotoxicity in rats. Tissue and Cell, 72, 101526. https://doi.org/10.1016/j.tice.2021.101526
  32. Kuzu, M., Kandemir, F. M., Yıldırım, S., Çağlayan, C., & Küçükler, S. (2021). Attenuation of sodium arsenite-induced cardiotoxicity and neurotoxicity with the antioxidant, anti-inflammatory, and antiapoptotic effects of hesperidin. Environ. Sci. Pollut. Res., 28, 10818-10831. https://doi.org/10.1007/s11356-020-11327-5
  33. Küçükler, S., Kandemir, F. M., Özdemir, S., Çomaklı, S., & Caglayan, C. (2021). Protective effects of rutin against deltamethrin-induced hepatotoxicity and nephrotoxicity in rats via regulation of oxidative stress, inflammation, and apoptosis. Environ. Sci. Pollut. Res., 28, 62975-62990. https://doi.org/10.1007/s11356-021-15190-w
  34. Livak KJ, Schmittgen TD (2001): Analysis of relative gene expression data using real-time quantitative PCR and the 2− ΔΔCT method. Methods, 25, 402-408. https://doi.org/10.1006/meth.2001.1262
  35. Lowry, O. H., Rosebrough, N. J., Farr, A. L., & Randall, R. J. (1951). Protein measurement with the Folin phenol reagent. J. Biol. Chem., 193(1), 265-275.
  36. Matkovics, B. (1988). Determination of enzyme activity in lipid peroxidation and glutathione pathways. Laboratoriumi Diagnosztika, 15, 248-250.
  37. Nanau, R. M., & Neuman, M. G. (2013). Adverse drug reactions induced by valproic acid. Clin. Biochem., 46(15), 1323-1338. https://doi.org/10.1016/j.clinbiochem.2013.06.012
  38. Oztay, F., Tunali, S., Kayalar, O., & Yanardag, R. (2020). The protective effect of vitamin U on valproic acid‐induced lung toxicity in rats via amelioration of oxidative stress. J. Biochem. Mol. Toxicol., 34(12), e22602. https://doi.org/10.1002/jbt.22602
  39. Placer, Z. A., Cushman, L. L., & Johnson, B. C. (1966). Estimation of product of lipid peroxidation (malonyl dialdehyde) in biochemical systems. Anal. Biochem, 16(2), 359-364.
  40. Sedlak, J., & Lindsay, R. H. (1968). Estimation of total, protein-bound, and nonprotein sulfhydryl groups in tissue with Ellman's reagent. Anal. Biochem., 25, 192-205.
  41. Semis, H. S., Gur, C., Ileriturk, M., Kandemir, F. M., & Kaynar, O. (2022). Evaluation of therapeutic effects of quercetin against Achilles tendinopathy in rats via oxidative stress, inflammation, apoptosis, autophagy, and metalloproteinases. Am.J. Sports Med., 50(2), 486-498. https://doi.org/10.1177/03635465211059821
  42. Semis, H. S., Kandemir, F.M., Kaynar, Ö., Dogan, T., & Arikan, Ş.M. (2021). The protective effects of hesperidin against paclitaxel-induced peripheral neuropathy in rats. Life Sci. 287: 120104. https://doi.org/10.1016/j.lfs.2021.120104
  43. Sun, Y. I., Oberley, L. W., & Li, Y. (1988). A simple method for clinical assay of superoxide dismutase. Clin. Chem., 34(3), 497-500.
  44. Şimşek, H., Demiryürek, Ş., Demir, T., Atabay, H. D., Çeribasi, A. O., Bayraktar, R., Kaplan, D. S., Öztuzcu, S., & Cengiz, B. (2016). Assessment of expressions of Bcl-XL, b-FGF, Bmp-2, Caspase-3, PDGFR-α, Smad1 and TGF-β1 genes in a rat model of lung ischemia/reperfusion. Iranian journal of basic medical sciences, 19(2), 209–214.
  45. Simsek, H., & Akaras, N. (2023). Acacetin ameliorates acetylsalicylic acid-induced gastric ulcer in rats by interfering with oxidative stress, inflammation, and apoptosis. International Journal of Medical Biochemistry, 6(2).
  46. Şimşek, H., Akaras, N., Gür, C., Küçükler, S., & Kandemir, F. M. (2023a). 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
  47. Şimşek, H., Küçükler, S., Gür, C., İleritürk, M., Aygörmez, S., & Kandemir, F. M. (2023b). Protective effects of zingerone against sodium arsenite-induced lung toxicity: A multi-biomarker approach. Iran. J. Basic Med. Sci., 26(9), 1098. https://dx.doi.org/10.22038/IJBMS.2023.71905.15623
  48. Şimşek, H., Küçükler, S., Gür, C., Akaras, N., & Kandemir, F. M. (2023). Protective effects of sinapic acid against lead acetate-induced nephrotoxicity: a multi-biomarker approach. Environmental Science and Pollution Research, 30(45), 101208-101222.
  49. Tabeshpour, J., Mehri, S., Abnous, K., & Hosseinzadeh, H. (2020). Role of oxidative stress, MAPKinase and apoptosis pathways in the protective effects of thymoquinone against acrylamide-induced central nervous system toxicity in rat. Neurochem. Res., 45, 254-267. https://doi.org/10.1007/s11064-019-02908-z
  50. Tuncer, S. Ç., Akarsu, S. A., Küçükler, S., Gür, C., & Kandemir, F. M. (2023a). Effects of sinapic acid on lead acetate‐induced oxidative stress, apoptosis and inflammation in testicular tissue. Environ. Toxicol., 38(11), 2656-2667. https://doi.org/10.1002/tox.23900
  51. Tuncer, S. Ç., Gür, C., Akaras, N., & Kandemir, F. M. (2023b). Protectıve Effect of Rutın on Oxidative Stress, Inflammation and Apoptosis in Valproat-Induced Gastrıc Toxicity. Med. J. SDU., 30(3), 334-342. https://dx.doi.org/10.17343/sdutfd.1251167
  52. Tuncer, S. Ç., Küçükler, S., Gür, C., Aygörmez, S., & Kandemir, F. M. (2023c). Effects of chrysin in cadmium-induced testicular toxicity in the rat; role of multi-pathway regulation. Mol. Biol. Rep., 50(10), 8305-8318.https://doi.org/10.1007/s11033-023-08715-8
  53. Yesildag, K., Gur, C., Ileriturk, M., & Kandemir, F. M. (2022). Evaluation of oxidative stress, inflammation, apoptosis, oxidative DNA damage and metalloproteinases in the lungs of rats treated with cadmium and carvacrol. Mol. Biol. Rep., 1-11.https://doi.org/10.1007/s11033-021-06948-z
  54. Yıldız, M. O., Çelik, H., Caglayan, C., Kandemir, F. M., Gür, C., Bayav, İ. & Kandemir, Ö. (2022). Neuromodulatory effects of hesperidin against sodium fluoride-induced neurotoxicity in rats: Involvement of neuroinflammation, endoplasmic reticulum stress, apoptosis and autophagy. Neurotoxicology, 90, 197-204.https://doi.org/10.1016/j.neuro.2022.04.002
  55. Zhou, L., Chen, L., Zeng, X., Liao, J., & Ouyang, D. (2020). Ginsenoside compound K alleviates sodium valproate-induced hepatotoxicity in rats via antioxidant effect, regulation of peroxisome pathway and iron homeostasis. Toxicol. Appl. Pharmacol., 386, 114829. https://doi.org/10.1016/j.taap.2019.114829
  56. Akcılar, R., Akcılar, A., Koçak, C., Koçak, F. E., Bayat, Z., Şimşek, H.,. & Savran, B. (2015b). Effects of Ukrain on intestinal apoptosis caused by ischemia-reperfusion injury in rats. International Journal of Clinical and Experimental Medicine, 8(12), 22158.
  57. Ekinci Akdemir, F. N., Yildirim, S., Kandemir, F. M., Aksu, E. H., Guler, M. C., Kiziltunc Ozmen, H.,. & Eser, G. (2019). The antiapoptotic and antioxidant effects of eugenol against cisplatin‐induced testicular damage in the experimental model. Andrologia, 51(9), e13353. https://doi.org/10.1111/and.13353
  58. Kankılıç, N. A., Şimşek, H., Akaras, N., Gür, C., İleritürk, M., Küçükler, S.,. & Kandemir, F. M. (2024a). 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. J. Biochem. Mol. Toxicol., 38(2), e23643. https://doi.org/10.1002/jbt.23643
  59. Kankılıç, N. A., Küçükler, S., Gür, C., Akarsu, S. A., Akaras, N., Şimşek, H.,. & Kandemir, F. M. (2024c). Naringin protects against paclitaxel‐induced toxicity in rat testicular tissues by regulating genes in pro‐inflammatory cytokines, oxidative stress, apoptosis, and JNK/MAPK signaling pathways. J. Biochem. Mol. Toxicol, 38(7), e23751. https://doi.org/10.1002/jbt.23751
  60. Kankılıç, N. A., Şimşek, H., Akaras, N., Gür, C., Küçükler, S., İleritürk, M.,. & Kandemir, F. M. (2024). The ameliorative effects of chrysin on bortezomib-induced nephrotoxicity in rats: reduces oxidative stress, endoplasmic reticulum stress, inflammation damage, apoptotic and autophagic death. Food Chem. Toxicol., 114791. https://doi.org/10.1016/j.fct.2024.114791
  61. Kocak, C., Kocak, F. E., Akcilar, R., Isiklar, O. O., Kocak, H., Bayat, Z.,. & Altuntas, I. (2016). Molecular and biochemical evidence on the protective effects of embelin and carnosic acid in isoproterenol-induced acute myocardial injury in rats. Life sciences, 147, 15-23. https://doi.org/10.1016/j.lfs.2016.01.038
  62. Koroglu, O. F., Gunata, M., Vardi, N., Yildiz, A., Ates, B., Colak, C.,. & Parlakpinar, H. (2021). Protective effects of naringin on valproic acid-induced hepatotoxicity in rats. Tissue and Cell, 72, 101526. https://doi.org/10.1016/j.tice.2021.101526