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Protective Effects of Morin Against Paracetamol-Induced Nephrotoxicity via Modulation of Oxidative Stress, Inflammation, and Apoptosis Pathways

Yıl 2025, Cilt: 14 Sayı: 3, 30 - 39, 26.09.2025
https://doi.org/10.46810/tdfd.1691320

Öz

Objective: Paracetamol (PCM), although a widely used and non-prescription effective analgesic and antipyretic, can cause nephrotoxicity by causing kidney damage at high doses. Morin (MRN) is a flavonoid found in white mulberry and cranberry, with low toxicity and prominent antioxidant, anti-inflammatory, and antiapoptotic properties. This study aimed to investigate the effects of MRN on PCM-induced kidney toxicity by biochemical, molecular, and histopathological methods.
Materials-Methods: Thirty-five Wistar rats were divided into Control, MRN (100 mg/kg), PCM (1000 mg/kg), PCM+MRN50 (50 mg/kg), and PCM+MRN100 (100 mg/kg) groups (n=7); the substances were administered orally for 6 days. The blood and kidney tissues were evaluated with biochemical (urea, creatinine, MDA, GSH, SOD, CAT, GPx), genetic (NF-κB, TNF-α, Caspase-3, Bax, Bcl-2, KIM-1, AQP2) and histopathological methods.
Results: While PCM negatively affected kidney function tests, oxidative stress levels, inflammation, and apoptosis markers and caused kidney damage, MRN suppressed these negative effects at both doses, improved kidney function, antioxidant defense, inflammation, and apoptosis parameters, and reduced histopathological damage.
Conclusion: The study found that MRN effectively protected kidney tissue from PCM-induced damage by reversing oxidative stress, inflammation, and apoptosis.

Kaynakça

  • Koç A, Erken HA, Koçak FE, Yay A, Güçlü A, Sari E, et al. Nephrotoxic effects of varenicline as the most effective drug used for smoking cessation: a preliminary experimental study. Int Urol Nephrol. 2015;47:823-29.
  • Topal I, Özdamar MY, Catakli T, Malkoc İ, Hacimuftuoglu A, Mamoulakis C, et al. Renoprotective effect of taxifolin in paracetamol-induced nephrotoxicity: emerging evidence from an animal model. J Clin Med. 2023;12(3):876.
  • Nazir N, Muhammad J, Ghaffar R, Nisar M, Zahoor M, Uddin F, et al. Phytochemical profiling and antioxidant potential of Daphne mucronata Royle and action against paracetamol-induced hepatotoxicity and nephrotoxicity in rabbits. Saudi J Biol Sci. 2021;28(9):5290-5301.
  • Çoban FK, İnce S, Demirel HH, İslam İ, Aytuğ H. Acetaminophen-induced nephrotoxicity: suppression of apoptosis and endoplasmic reticulum stress using boric acid. Biol Trace Elem Res. 2023;201(1):242-49.
  • Şimşek H, Akaras N, Gür C, Küçükler S, İleritürk M, Kandemir FM. Ameliorative effect of morin on diclofenac-induced testicular toxicity in rats: An investigation into different signal pathways. Iran J Basic Med Sci. 2025;28(4):507.
  • Özdemir S, Kucukler S, Çomaklı S, Kandemir FM. The protective effect of Morin against ifosfamide-induced acute liver injury in rats associated with the inhibition of DNA damage and apoptosis. Drug Chem Toxicol. 2022;45(3):1308-17.
  • Öztürk, A. B., Şimşek, H., Akaras, N., & Kandemir, F. M. (2025). Effects of Morin on the Wnt, Notch1/Hes1, KI-67/3-Nitrotyrosine and Damage Signaling Pathways in Rats Subjected to Experimental Testicular Ischemia/Reperfusion. Bratislava Medical Journal, 1-20.
  • Gur, C., Kandemir, F. M., Darendelioglu, E., Caglayan, C., Kucukler, S., Kandemir, O., & Ileriturk, M. (2021). Morin protects against acrylamide-induced neurotoxicity in rats: an investigation into different signal pathways. Environmental Science and Pollution Research, 28(36), 49808-19.
  • Aygörmez S, Küçükler S, Akaras N, Maraşlı Ş, Kandemir FM. Investigation of the effects of Morin on potassium bromate-induced brain damage in rats via different pathways with biochemical and histopathological methods. Food Chem Toxicol. 2025;115466.
  • Çomaklı S, Kandemir FM, Küçükler S, Özdemir S. Morin mitigates ifosfamide induced nephrotoxicity by regulation of NF-kappaB/p53 and Bcl-2 expression. Biotechnic Histochem. 2022;97(6):423-32.
  • Kandemir FM, Yıldırım S, Kucukler S, Caglayan C, Darendelioğlu E, Dortbudak MB. Protective effects of morin against acrylamide-induced hepatotoxicity and nephrotoxicity: A multi-biomarker approach. Food Chem Toxicol. 2020;138:111190.
  • Ucar F, Taslipinar MY, Alp BF, Aydin I, Aydin FN, Agilli M, et al. The effects of N-acetylcysteine and ozone therapy on oxidative stress and inflammation in acetaminophen-induced nephrotoxicity model. Ren Fail. 2013;35(5):640-47.
  • Matkovics B. Determination of enzyme activity in lipid peroxidation and glutathione pathways. Laboratoriumi Diagnosztika. 1988;15:248-50.
  • Sedlak J, Lindsay RH. Estimation of total, protein-bound, and nonprotein sulfhydryl groups in tissue with Ellman's reagent. Anal Biochem. 1968;25:192-205.
  • Placer ZA, Cushman LL, Johnson BC. Estimation of product of lipid peroxidation (malonyl dialdehyde) in biochemical systems. Anal Biochem. 1966;16(2):359-64.
  • Sun YI, Oberley LW, Li Y. A simple method for clinical assay of superoxide dismutase. Clin Chem. 1988;34(3):497-500.
  • Aebi H. Catalase in vitro. In: Methods in Enzymology. Vol. 105. Academic press; 1984. p. 121-26.
  • Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951;193(1):265-75.
  • Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 2001;25(4):402-08.
  • Kandemir Ö, Akaras N, Şimşek H, Gür C, İleritürk M, Küçükler S, et al. Nephroprotective effects of hesperidin on ifosfamide-induced acute nephrotoxicity in rats: Role of NF-κB/TNF-α/IL-1β, p53/caspase-3/Bax/Bcl-2, and ATF6/IRE1/PERK/GRP78 signaling pathways. Arch Biochem Biophys. 2025;110465.
  • Ahmad I, Alam W, Pirzada AS, Darwish HW, Zafar R, Daglia M, et al. Oxindole derivatives alleviate paracetamol-induced nephrotoxicity and hepatotoxicity: biochemical, histological, and computational expressions. Naunyn Schmiedebergs Arch Pharmacol. 2024:1-13.
  • Akaras N, Toktay E, Celep NA, Yüce N, Şimşek H, Özkan Hİ. Antioxidant effects of bromelain on paracetamol-induced renal injury in rats. Arch Basic Clin Res. 2023;5:364-71.
  • Chinnappan SM, George A, Thaggikuppe P, Choudhary Y, Choudhary VK, Ramani Y, et al. Nephroprotective effect of herbal extract Eurycoma longifolia on paracetamol-induced nephrotoxicity in rats. Evid Based Complement Alternat Med. 2019;2019(1):4916519.
  • Divyashree R, Sultanpur CM. Protective effect of Acacia Ferruginea bark extract against paracetamol-induced nephrotoxicity in rats. RGUHS J Pharm Sci. 2025;15(1).
  • Althagafy HS, Hassanein EH. Morin mitigates 5-Fluorouracil-induced nephrotoxicity by activating Nrf2/HO-1 and FXR, and suppressing ERK/VCAM-1 and NF-κB pathways. Int Immunopharmacol. 2025;148:114092.
  • Darendelioğlu E, Sağ S, Caglayan C. Assessment of morin hydrate as a renal protective agent in rats subjected to methotrexate-induced nephrotoxicity. Drug Chem Toxicol. 2025;48(1):172-79.
  • Ahmad MM, Rezk NA, Fawzy A, Sabry M. Protective effects of curcumin and silymarin against paracetamol-induced hepatotoxicity in adult male albino rats. Gene. 2019;712:143966.
  • KELEŞ O, Can S, Cigsar G, Colak S, Erol H, Akaras N, et al. Hepatoprotective effects of B-1, 3-(D)-glucan on bortezomib-induced liver damage in rats. Kafkas Univ Vet Fak Derg. 2014;20(6).
  • Ozyigit F, Deger AN, Kocak FE, Ekici MF, Simsek H, Arık O. Protective effects of hesperidin in gastric damage caused by experimental ischemia-reperfusion injury model in rats. Acta Cir Bras. 2024;39:e391124.
  • Yıldız MO, Çelik H, Caglayan C, Kandemir FM, Gür C, Bayav İ, et al. Neuromodulatory effects of hesperidin against sodium fluoride-induced neurotoxicity in rats: Involvement of neuroinflammation, endoplasmic reticulum stress, apoptosis and autophagy. Neurotoxicol. 2022;90:197-204.
  • Akaras N, Gur C, Kucukler S, Kandemir FM. Zingerone reduces sodium arsenite-induced nephrotoxicity by regulating oxidative stress, inflammation, apoptosis and histopathological changes. Chem Biol Interact. 2023;374:110410.
  • Şimşek H, Akaras N, Gür C, Küçükler S, Kandemir FM. 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. 2023;875:147502.
  • Yousef MI, Omar SA, El-Guendi MI, Abdelmegid LA. Potential protective effects of quercetin and curcumin on paracetamol-induced histological changes, oxidative stress, impaired liver and kidney functions and haematotoxicity in rat. Food Chem Toxicol. 2010;48(11):3246-61.
  • Kızıl, H. E., Caglayan, C., Darendelioğlu, E., Ayna, A., Gür, C., Kandemir, F. M., & Küçükler, S. (2023). Morin ameliorates methotrexate-induced hepatotoxicity via targeting Nrf2/HO-1 and Bax/Bcl2/Caspase-3 signaling pathways. Molecular Biology Reports, 50(4), 3479-88.
  • Aydin M, Cevik A, Kandemir FM, Yuksel M, Apaydin AM. Evaluation of hormonal change, biochemical parameters, and histopathological status of uterus in rats exposed to 50-Hz electromagnetic field. Toxicol Ind Health. 2009;25(3): 153-58.
  • Aksu EH, Kandemir FM, Yıldırım S, Küçükler S, Dörtbudak MB, Çağlayan C, et al. Palliative effect of curcumin on doxorubicin‐induced testicular damage in male rats. J Biochem Mol Toxicol. 2019;33(10):e22384.
  • Kandemir FM, Kucukler S, Eldutar E, Caglayan C, Gülçin İ. Chrysin protects rat kidney from paracetamol-induced oxidative stress, inflammation, apoptosis, and autophagy: a multi-biomarker approach. Sci Pharm. 2017;85(1):4.
  • Ileriturk M, Kandemir O, Akaras N, Simsek H, Genc A, Kandemir FM. Hesperidin has a protective effect on paclitaxel-induced testicular toxicity through regulating oxidative stress, apoptosis, inflammation and endoplasmic reticulum stress. Reprod Toxicol. 2023;118:108369.
  • Kucukler S, Benzer F, Yildirim S, Gur C, Kandemir FM, Bengu AS, et al. Protective effects of chrysin against oxidative stress and inflammation induced by lead acetate in rat kidneys: a biochemical and histopathological approach. Biol Trace Elem Res. 2021;199(4):1501-14.
  • Çağlayan C, Kandemir FM, Darendelioğlu E, Küçükler S, Ayna A. Hesperidin protects liver and kidney against sodium fluoride-induced toxicity through anti-apoptotic and anti-autophagic mechanisms. Life Sci. 2021;281:119730.
  • Kankılıç NA, Şimşek H, Akaras N, Gür C, Küçükler S, İleritürk M, et al. 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. 2024;190:114791.
  • Akaras N, Kandemir FM, Şimşek H, Gür C, Aygörmez S. Antioxidant, antiinflammatory, and antiapoptotic effects of rutin in spleen toxicity induced by sodium valproate in rats. Turk J Nat Sci. 2023;12(2):138–44.
  • Yilmaz S, Gur C, Kucukler S, Akaras N, Kandemir FM. Zingerone attenuates sciatic nerve damage caused by sodium arsenite by inhibiting NF-κB, caspase-3, and ATF-6/CHOP pathways and activating the Akt2/FOXO1 pathway. Iran J Basic Med Sci. 2024;27(4):485.
  • Gencer S, Gür C, İleritürk M, Küçükler S, Akaras N, Şimşek H, et al. The ameliorative effect of carvacrol on sodium arsenite‐induced hepatotoxicity in rats: Possible role of Nrf2/HO‐1, RAGE/NLRP3, Bax/Bcl‐2/Caspase‐3, and Beclin‐1 pathways. J Biochem Mol Toxicol. 2024;38(10):e23863.
  • El-Boshy M, BaSalamah MA, Ahmad J, Idris S, Mahbub A, Abdelghany AH, et al. Vitamin D protects against oxidative stress, inflammation and hepatorenal damage induced by acute paracetamol toxicity in rat. Free Radic Biol Med. 2019;141:310–21.
  • Akaras N, Gür C, Caglayan C, Kandemir FM. Protective effects of naringin against oxaliplatin-induced testicular damage in rats: Involvement of oxidative stress, inflammation, endoplasmic reticulum stress, apoptosis, and histopathology. Iran J Basic Med Sci. 2024;27(4):466.
  • Bal TT, Akaras N, Demir Ö, Ugan RA. Protective effect of astaxanthin and metformin in the liver of rats in which the polycystic ovary syndrome model was formed by giving letrozole. Iran J Basic Med Sci. 2023;26(6):688.
  • Kankılıç NA, Küçükler S, Gür C, Akarsu SA, Akaras N, Şimşek H, et al. 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. 2024;38(7):e23751.
  • Akaras N, Kucukler S, Gur C, Ileriturk M, Kandemir FM. Sinapic acid protects against lead acetate‐induced lung toxicity by reducing oxidative stress, apoptosis, inflammation, and endoplasmic reticulum stress damage. Environ Toxicol. 2024;39(7):3820–32.
  • Küçükler S, Caglayan C, Özdemir S, Çomaklı S, Kandemir FM. Hesperidin counteracts chlorpyrifos-induced neurotoxicity by regulating oxidative stress, inflammation, and apoptosis in rats. Metab Brain Dis. 2024;39(4):509–22.
  • El-Bakry HA, El-Sherif G, Rostom RM. Therapeutic dose of green tea extract provokes liver damage and exacerbates paracetamol-induced hepatotoxicity in rats through oxidative stress and caspase 3-dependent apoptosis. Biomed Pharmacother. 2017;96:798–811.
  • Aktas Senocak E, Utlu N, Kurt S, Kucukler S, Kandemir FM. Sodium pentaborate prevents acetaminophen-induced hepatorenal injury by suppressing oxidative stress, lipid peroxidation, apoptosis, and inflammatory cytokines in rats. Biol Trace Elem Res. 2024;202(3):1164–73.

Morin’in Oksidatif Stres, İnflamasyon ve Apoptozis Yollarının Modülasyonu Yoluyla Parasetamol Kaynaklı Nefrotoksisiteye Karşı Koruyucu Etkileri

Yıl 2025, Cilt: 14 Sayı: 3, 30 - 39, 26.09.2025
https://doi.org/10.46810/tdfd.1691320

Öz

Amaç: Paracetamol (PCM), yaygın ve reçetesiz kullanılan etkili bir analjezik ve antipiretik olsa da, yüksek dozlarda böbrek hasarına neden olarak nefrotoksisiteye yol açabilir. Morin (MRN), beyaz dut ve kızılcıkta bulunan, düşük toksisiteye sahip, antioksidan, antiinflamatuvar ve antiapoptotik özellikleriyle öne çıkan bir flavonoiddir. Bu çalışmada, PCM’nin neden olduğu böbrek toksisitesi üzerine MRN'nin etkileri biyokimyasal, moleküler ve histopatolojik yöntemlerle araştırılması amaçlanmıştır.
Materyal-Metot: Otuz beş Wistar sıçan, Kontrol, MRN (100 mg/kg), PCM (1000mg/kg), PCM+MRN50 (50mg/kg) ve PCM+MRN100 (100mg/kg) gruplarına ayrılmış (n=7); maddeler 6 gün boyunca oral uygulanmıştır. Alınan kan ve böbrek dokuları biyokimyasal (üre, kreatinin, MDA, GSH, SOD, KAT, GPx), genetik (NF-κB, TNF-α, Caspase-3, Bax, Bcl-2, KIM-1, AQP2) ve histopatolojik yöntemlerle değerlendirilmiştir.
Bulgular: PCM böbrek fonksiyon testlerini, oksidatif stres düzeylerini, inflamasyon ve apoptoz belirteçlerini olumsuz etkileyip böbrek hasarı oluştururken; MRN her iki dozda bu olumsuz etkileri baskılayarak böbrek fonksiyonu, antioksidan savunma, inflamasyon ve apoptoz parametrelerini iyileştirmiş, histopatolojik hasarı azaltmıştır.
Sonuç: Çalışmada MRN'nin oksidatif stresi, inflamasyonu ve apoptozu tersine çevirerek böbrek dokusunu PCM kaynaklı hasardan etkili bir şekilde koruduğu bulunmuştur.

Kaynakça

  • Koç A, Erken HA, Koçak FE, Yay A, Güçlü A, Sari E, et al. Nephrotoxic effects of varenicline as the most effective drug used for smoking cessation: a preliminary experimental study. Int Urol Nephrol. 2015;47:823-29.
  • Topal I, Özdamar MY, Catakli T, Malkoc İ, Hacimuftuoglu A, Mamoulakis C, et al. Renoprotective effect of taxifolin in paracetamol-induced nephrotoxicity: emerging evidence from an animal model. J Clin Med. 2023;12(3):876.
  • Nazir N, Muhammad J, Ghaffar R, Nisar M, Zahoor M, Uddin F, et al. Phytochemical profiling and antioxidant potential of Daphne mucronata Royle and action against paracetamol-induced hepatotoxicity and nephrotoxicity in rabbits. Saudi J Biol Sci. 2021;28(9):5290-5301.
  • Çoban FK, İnce S, Demirel HH, İslam İ, Aytuğ H. Acetaminophen-induced nephrotoxicity: suppression of apoptosis and endoplasmic reticulum stress using boric acid. Biol Trace Elem Res. 2023;201(1):242-49.
  • Şimşek H, Akaras N, Gür C, Küçükler S, İleritürk M, Kandemir FM. Ameliorative effect of morin on diclofenac-induced testicular toxicity in rats: An investigation into different signal pathways. Iran J Basic Med Sci. 2025;28(4):507.
  • Özdemir S, Kucukler S, Çomaklı S, Kandemir FM. The protective effect of Morin against ifosfamide-induced acute liver injury in rats associated with the inhibition of DNA damage and apoptosis. Drug Chem Toxicol. 2022;45(3):1308-17.
  • Öztürk, A. B., Şimşek, H., Akaras, N., & Kandemir, F. M. (2025). Effects of Morin on the Wnt, Notch1/Hes1, KI-67/3-Nitrotyrosine and Damage Signaling Pathways in Rats Subjected to Experimental Testicular Ischemia/Reperfusion. Bratislava Medical Journal, 1-20.
  • Gur, C., Kandemir, F. M., Darendelioglu, E., Caglayan, C., Kucukler, S., Kandemir, O., & Ileriturk, M. (2021). Morin protects against acrylamide-induced neurotoxicity in rats: an investigation into different signal pathways. Environmental Science and Pollution Research, 28(36), 49808-19.
  • Aygörmez S, Küçükler S, Akaras N, Maraşlı Ş, Kandemir FM. Investigation of the effects of Morin on potassium bromate-induced brain damage in rats via different pathways with biochemical and histopathological methods. Food Chem Toxicol. 2025;115466.
  • Çomaklı S, Kandemir FM, Küçükler S, Özdemir S. Morin mitigates ifosfamide induced nephrotoxicity by regulation of NF-kappaB/p53 and Bcl-2 expression. Biotechnic Histochem. 2022;97(6):423-32.
  • Kandemir FM, Yıldırım S, Kucukler S, Caglayan C, Darendelioğlu E, Dortbudak MB. Protective effects of morin against acrylamide-induced hepatotoxicity and nephrotoxicity: A multi-biomarker approach. Food Chem Toxicol. 2020;138:111190.
  • Ucar F, Taslipinar MY, Alp BF, Aydin I, Aydin FN, Agilli M, et al. The effects of N-acetylcysteine and ozone therapy on oxidative stress and inflammation in acetaminophen-induced nephrotoxicity model. Ren Fail. 2013;35(5):640-47.
  • Matkovics B. Determination of enzyme activity in lipid peroxidation and glutathione pathways. Laboratoriumi Diagnosztika. 1988;15:248-50.
  • Sedlak J, Lindsay RH. Estimation of total, protein-bound, and nonprotein sulfhydryl groups in tissue with Ellman's reagent. Anal Biochem. 1968;25:192-205.
  • Placer ZA, Cushman LL, Johnson BC. Estimation of product of lipid peroxidation (malonyl dialdehyde) in biochemical systems. Anal Biochem. 1966;16(2):359-64.
  • Sun YI, Oberley LW, Li Y. A simple method for clinical assay of superoxide dismutase. Clin Chem. 1988;34(3):497-500.
  • Aebi H. Catalase in vitro. In: Methods in Enzymology. Vol. 105. Academic press; 1984. p. 121-26.
  • Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951;193(1):265-75.
  • Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 2001;25(4):402-08.
  • Kandemir Ö, Akaras N, Şimşek H, Gür C, İleritürk M, Küçükler S, et al. Nephroprotective effects of hesperidin on ifosfamide-induced acute nephrotoxicity in rats: Role of NF-κB/TNF-α/IL-1β, p53/caspase-3/Bax/Bcl-2, and ATF6/IRE1/PERK/GRP78 signaling pathways. Arch Biochem Biophys. 2025;110465.
  • Ahmad I, Alam W, Pirzada AS, Darwish HW, Zafar R, Daglia M, et al. Oxindole derivatives alleviate paracetamol-induced nephrotoxicity and hepatotoxicity: biochemical, histological, and computational expressions. Naunyn Schmiedebergs Arch Pharmacol. 2024:1-13.
  • Akaras N, Toktay E, Celep NA, Yüce N, Şimşek H, Özkan Hİ. Antioxidant effects of bromelain on paracetamol-induced renal injury in rats. Arch Basic Clin Res. 2023;5:364-71.
  • Chinnappan SM, George A, Thaggikuppe P, Choudhary Y, Choudhary VK, Ramani Y, et al. Nephroprotective effect of herbal extract Eurycoma longifolia on paracetamol-induced nephrotoxicity in rats. Evid Based Complement Alternat Med. 2019;2019(1):4916519.
  • Divyashree R, Sultanpur CM. Protective effect of Acacia Ferruginea bark extract against paracetamol-induced nephrotoxicity in rats. RGUHS J Pharm Sci. 2025;15(1).
  • Althagafy HS, Hassanein EH. Morin mitigates 5-Fluorouracil-induced nephrotoxicity by activating Nrf2/HO-1 and FXR, and suppressing ERK/VCAM-1 and NF-κB pathways. Int Immunopharmacol. 2025;148:114092.
  • Darendelioğlu E, Sağ S, Caglayan C. Assessment of morin hydrate as a renal protective agent in rats subjected to methotrexate-induced nephrotoxicity. Drug Chem Toxicol. 2025;48(1):172-79.
  • Ahmad MM, Rezk NA, Fawzy A, Sabry M. Protective effects of curcumin and silymarin against paracetamol-induced hepatotoxicity in adult male albino rats. Gene. 2019;712:143966.
  • KELEŞ O, Can S, Cigsar G, Colak S, Erol H, Akaras N, et al. Hepatoprotective effects of B-1, 3-(D)-glucan on bortezomib-induced liver damage in rats. Kafkas Univ Vet Fak Derg. 2014;20(6).
  • Ozyigit F, Deger AN, Kocak FE, Ekici MF, Simsek H, Arık O. Protective effects of hesperidin in gastric damage caused by experimental ischemia-reperfusion injury model in rats. Acta Cir Bras. 2024;39:e391124.
  • Yıldız MO, Çelik H, Caglayan C, Kandemir FM, Gür C, Bayav İ, et al. Neuromodulatory effects of hesperidin against sodium fluoride-induced neurotoxicity in rats: Involvement of neuroinflammation, endoplasmic reticulum stress, apoptosis and autophagy. Neurotoxicol. 2022;90:197-204.
  • Akaras N, Gur C, Kucukler S, Kandemir FM. Zingerone reduces sodium arsenite-induced nephrotoxicity by regulating oxidative stress, inflammation, apoptosis and histopathological changes. Chem Biol Interact. 2023;374:110410.
  • Şimşek H, Akaras N, Gür C, Küçükler S, Kandemir FM. 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. 2023;875:147502.
  • Yousef MI, Omar SA, El-Guendi MI, Abdelmegid LA. Potential protective effects of quercetin and curcumin on paracetamol-induced histological changes, oxidative stress, impaired liver and kidney functions and haematotoxicity in rat. Food Chem Toxicol. 2010;48(11):3246-61.
  • Kızıl, H. E., Caglayan, C., Darendelioğlu, E., Ayna, A., Gür, C., Kandemir, F. M., & Küçükler, S. (2023). Morin ameliorates methotrexate-induced hepatotoxicity via targeting Nrf2/HO-1 and Bax/Bcl2/Caspase-3 signaling pathways. Molecular Biology Reports, 50(4), 3479-88.
  • Aydin M, Cevik A, Kandemir FM, Yuksel M, Apaydin AM. Evaluation of hormonal change, biochemical parameters, and histopathological status of uterus in rats exposed to 50-Hz electromagnetic field. Toxicol Ind Health. 2009;25(3): 153-58.
  • Aksu EH, Kandemir FM, Yıldırım S, Küçükler S, Dörtbudak MB, Çağlayan C, et al. Palliative effect of curcumin on doxorubicin‐induced testicular damage in male rats. J Biochem Mol Toxicol. 2019;33(10):e22384.
  • Kandemir FM, Kucukler S, Eldutar E, Caglayan C, Gülçin İ. Chrysin protects rat kidney from paracetamol-induced oxidative stress, inflammation, apoptosis, and autophagy: a multi-biomarker approach. Sci Pharm. 2017;85(1):4.
  • Ileriturk M, Kandemir O, Akaras N, Simsek H, Genc A, Kandemir FM. Hesperidin has a protective effect on paclitaxel-induced testicular toxicity through regulating oxidative stress, apoptosis, inflammation and endoplasmic reticulum stress. Reprod Toxicol. 2023;118:108369.
  • Kucukler S, Benzer F, Yildirim S, Gur C, Kandemir FM, Bengu AS, et al. Protective effects of chrysin against oxidative stress and inflammation induced by lead acetate in rat kidneys: a biochemical and histopathological approach. Biol Trace Elem Res. 2021;199(4):1501-14.
  • Çağlayan C, Kandemir FM, Darendelioğlu E, Küçükler S, Ayna A. Hesperidin protects liver and kidney against sodium fluoride-induced toxicity through anti-apoptotic and anti-autophagic mechanisms. Life Sci. 2021;281:119730.
  • Kankılıç NA, Şimşek H, Akaras N, Gür C, Küçükler S, İleritürk M, et al. 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. 2024;190:114791.
  • Akaras N, Kandemir FM, Şimşek H, Gür C, Aygörmez S. Antioxidant, antiinflammatory, and antiapoptotic effects of rutin in spleen toxicity induced by sodium valproate in rats. Turk J Nat Sci. 2023;12(2):138–44.
  • Yilmaz S, Gur C, Kucukler S, Akaras N, Kandemir FM. Zingerone attenuates sciatic nerve damage caused by sodium arsenite by inhibiting NF-κB, caspase-3, and ATF-6/CHOP pathways and activating the Akt2/FOXO1 pathway. Iran J Basic Med Sci. 2024;27(4):485.
  • Gencer S, Gür C, İleritürk M, Küçükler S, Akaras N, Şimşek H, et al. The ameliorative effect of carvacrol on sodium arsenite‐induced hepatotoxicity in rats: Possible role of Nrf2/HO‐1, RAGE/NLRP3, Bax/Bcl‐2/Caspase‐3, and Beclin‐1 pathways. J Biochem Mol Toxicol. 2024;38(10):e23863.
  • El-Boshy M, BaSalamah MA, Ahmad J, Idris S, Mahbub A, Abdelghany AH, et al. Vitamin D protects against oxidative stress, inflammation and hepatorenal damage induced by acute paracetamol toxicity in rat. Free Radic Biol Med. 2019;141:310–21.
  • Akaras N, Gür C, Caglayan C, Kandemir FM. Protective effects of naringin against oxaliplatin-induced testicular damage in rats: Involvement of oxidative stress, inflammation, endoplasmic reticulum stress, apoptosis, and histopathology. Iran J Basic Med Sci. 2024;27(4):466.
  • Bal TT, Akaras N, Demir Ö, Ugan RA. Protective effect of astaxanthin and metformin in the liver of rats in which the polycystic ovary syndrome model was formed by giving letrozole. Iran J Basic Med Sci. 2023;26(6):688.
  • Kankılıç NA, Küçükler S, Gür C, Akarsu SA, Akaras N, Şimşek H, et al. 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. 2024;38(7):e23751.
  • Akaras N, Kucukler S, Gur C, Ileriturk M, Kandemir FM. Sinapic acid protects against lead acetate‐induced lung toxicity by reducing oxidative stress, apoptosis, inflammation, and endoplasmic reticulum stress damage. Environ Toxicol. 2024;39(7):3820–32.
  • Küçükler S, Caglayan C, Özdemir S, Çomaklı S, Kandemir FM. Hesperidin counteracts chlorpyrifos-induced neurotoxicity by regulating oxidative stress, inflammation, and apoptosis in rats. Metab Brain Dis. 2024;39(4):509–22.
  • El-Bakry HA, El-Sherif G, Rostom RM. Therapeutic dose of green tea extract provokes liver damage and exacerbates paracetamol-induced hepatotoxicity in rats through oxidative stress and caspase 3-dependent apoptosis. Biomed Pharmacother. 2017;96:798–811.
  • Aktas Senocak E, Utlu N, Kurt S, Kucukler S, Kandemir FM. Sodium pentaborate prevents acetaminophen-induced hepatorenal injury by suppressing oxidative stress, lipid peroxidation, apoptosis, and inflammatory cytokines in rats. Biol Trace Elem Res. 2024;202(3):1164–73.
Toplam 52 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Konular Biyokimya ve Hücre Biyolojisi (Diğer)
Bölüm Makaleler
Yazarlar

Özge Kandemir 0000-0001-8884-4168

Fatih Mehmet Kandemir 0000-0002-8490-2479

Nurhan Akaras 0000-0002-8457-9448

Hasan Şimşek 0000-0001-5573-4923

Yayımlanma Tarihi 26 Eylül 2025
Gönderilme Tarihi 4 Mayıs 2025
Kabul Tarihi 23 Haziran 2025
Yayımlandığı Sayı Yıl 2025 Cilt: 14 Sayı: 3

Kaynak Göster

APA Kandemir, Ö., Kandemir, F. M., Akaras, N., Şimşek, H. (2025). Protective Effects of Morin Against Paracetamol-Induced Nephrotoxicity via Modulation of Oxidative Stress, Inflammation, and Apoptosis Pathways. Türk Doğa ve Fen Dergisi, 14(3), 30-39. https://doi.org/10.46810/tdfd.1691320
AMA Kandemir Ö, Kandemir FM, Akaras N, Şimşek H. Protective Effects of Morin Against Paracetamol-Induced Nephrotoxicity via Modulation of Oxidative Stress, Inflammation, and Apoptosis Pathways. TDFD. Eylül 2025;14(3):30-39. doi:10.46810/tdfd.1691320
Chicago Kandemir, Özge, Fatih Mehmet Kandemir, Nurhan Akaras, ve Hasan Şimşek. “Protective Effects of Morin Against Paracetamol-Induced Nephrotoxicity via Modulation of Oxidative Stress, Inflammation, and Apoptosis Pathways”. Türk Doğa ve Fen Dergisi 14, sy. 3 (Eylül 2025): 30-39. https://doi.org/10.46810/tdfd.1691320.
EndNote Kandemir Ö, Kandemir FM, Akaras N, Şimşek H (01 Eylül 2025) Protective Effects of Morin Against Paracetamol-Induced Nephrotoxicity via Modulation of Oxidative Stress, Inflammation, and Apoptosis Pathways. Türk Doğa ve Fen Dergisi 14 3 30–39.
IEEE Ö. Kandemir, F. M. Kandemir, N. Akaras, ve H. Şimşek, “Protective Effects of Morin Against Paracetamol-Induced Nephrotoxicity via Modulation of Oxidative Stress, Inflammation, and Apoptosis Pathways”, TDFD, c. 14, sy. 3, ss. 30–39, 2025, doi: 10.46810/tdfd.1691320.
ISNAD Kandemir, Özge vd. “Protective Effects of Morin Against Paracetamol-Induced Nephrotoxicity via Modulation of Oxidative Stress, Inflammation, and Apoptosis Pathways”. Türk Doğa ve Fen Dergisi 14/3 (Eylül2025), 30-39. https://doi.org/10.46810/tdfd.1691320.
JAMA Kandemir Ö, Kandemir FM, Akaras N, Şimşek H. Protective Effects of Morin Against Paracetamol-Induced Nephrotoxicity via Modulation of Oxidative Stress, Inflammation, and Apoptosis Pathways. TDFD. 2025;14:30–39.
MLA Kandemir, Özge vd. “Protective Effects of Morin Against Paracetamol-Induced Nephrotoxicity via Modulation of Oxidative Stress, Inflammation, and Apoptosis Pathways”. Türk Doğa ve Fen Dergisi, c. 14, sy. 3, 2025, ss. 30-39, doi:10.46810/tdfd.1691320.
Vancouver Kandemir Ö, Kandemir FM, Akaras N, Şimşek H. Protective Effects of Morin Against Paracetamol-Induced Nephrotoxicity via Modulation of Oxidative Stress, Inflammation, and Apoptosis Pathways. TDFD. 2025;14(3):30-9.