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Journals / İstanbul Gelişim Üniversitesi Sağlık Bilimleri Dergisi / 2026 / Sayı: 30

Nephroprotective Effect of Apilarnil in Acetaminophen-Induced Acute Kidney Injury Model

Asetaminofen ile İndüklenen Akut Böbrek Hasarı Modelinde Apilarnilin Nefroprotektif Etkisi

Nurcan Bıçakçı(TEKİRDAĞ NAMIK KEMAL ÜNİVERSİTESİ)0000-0003-1358-9224
Sercan Bıçakçı(TEKİRDAĞ NAMIK KEMAL ÜNİVERSİTESİ)0000-0002-3268-0499
İhsan Karaboğa(KIRKLARELİ ÜNİVERSİTESİ)0000-0001-6708-1229
Pages
399–410
Publication Date
2026-08-31
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AI Summary & Key Takeaways

AI Insight
⚡ TL;DR(Too Long; Didn't Read)

AP may be an option that can be used for the treatment of high-dose paracetamol-induced renal damage.

📌 3 Key Takeaways

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Objective & Hypothesis:Aim: High-dose and long-term acetaminophen (paracetamol; PAR) use can cause acute and chronic kidney damage.
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Key Findings & Data:Method: A total of 32 adult male Wistar albino rats were used in this study.
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Conclusion & Impact:AP may be an option that can be used for the treatment of high-dose paracetamol-induced renal damage.
🔬Design:Modeling & Simulation
📍Scope:Comprehensive Sample
⚙️Variables:Asetaminofen · apilarnil · akut böbrek hasarı

Abstract

Aim: High-dose and long-term acetaminophen (paracetamol; PAR) use can cause acute and chronic kidney damage. It was reported that apilarnil (AP), an apitherapy product obtained from drone larvae, has high antioxidative and anti-inflammatory effects. In this study, the effect of apilarnil on kidney tissue damage, oxidative status, and inflammation in an acetaminophen-induced renal injury model was investigated. Method: A total of 32 adult male Wistar albino rats were used in this study. Rats were divided into 4 groups as control, paracetamol (PAR), paracetamol+apilarnil (PAR+AP) and apilarnil (AP) groups. A dose of 600 mg/kg PAR was used to create the acute kidney injury model. AP was administered at a dose of 0.8 mg/kg. Kidney tissue histopathology was evaluated with the hematoxylin-eosin (H&E) staining method. Renal tumor necrosis factor α (TNF-α) expression was determined by the indirect immunohistochemical method. Renal glutathione peroxidase (GPx), superoxide dismutase (SOD), catalase (CAT) and malondialdehyde (MDA) levels were determined by the ELISA method. Results: PAR administration caused an increase in MDA level in kidney tissue, while antioxidant enzyme levels of SOD, CAT and GPx decreased. PAR also caused an increase in renal TNF-α immunohistochemical expression. AP treatment provided a significant decrease in MDA level, while GPx and SOD levels increased. AP treatment also provided a decrease in renal TNF-α expression and tubular damage score. Conclusion: This study is the first report showing that AP prevents paracetamol-induced renal damage. AP may be an option that can be used for the treatment of high-dose paracetamol-induced renal damage.

Özet

Amaç: Yüksek doz ve uzun süre Asetaminofen (parasetamol) kullanımı akut ve kronik böbrek hasarına neden olabilmektedir. Erkek arı larvasından elde edilen bir apiterapik ürün olan apilarnilin, yüksek antioksidatif ve antiinflamatuvar etkilere sahip olduğu belirtilmiştir. Bu çalışmada asetaminofen-uyarımlı renal hasar modelinde apilarnilin böbrek doku hasarı, oksidatif statü ve inflamasyon üzerindeki etkisi incelendi. Yöntem: Çalışmada 32 adet erişkin erkek Wistar albino sıçan kullanıldı. Sıçanlar kontrol, parasetamol (PAR), parasetamol+apilarnil (PAR+AP) ve apilarnil (AP) olarak 4 gruba ayrıldı. Akut böbrek hasar modeli oluşturmada 600 mg/kg PAR kullanıldı. AP 0,8 mg/kg dozda uygulandı. Böbrek doku histopatolojisi hematoksilen – eozin (H&E) boyama yöntemi ile değerlendirildi. Renal TNF-α ifadesi indirekt immünohistokimyasal yöntemle belirlendi. Renal glutatyon peroksidaz (GPx), süperoksit dismutaz (SOD), katalaz (CAT) ve Malondialdehit (MDA) seviyeleri ELISA yöntemi ile belirlendi. Bulgular: PAR uygulaması böbrek dokusunda MDA seviyesinde artışa neden olurken; antioksidan enzimler SOD, CAT ve GPx seviyelerinde azalmaya neden oldu. Ayrıca PAR, renal TNF-α immünohistokimyasal ifadesinde artışa neden oldu. AP tedavisi MDA seviyesinde anlamlı bir azalma sağlarken, GPx ve SOD seviyesinde artış sağladı. Ayrıca AP uygulaması renal TNF-α ifadesi ve tübüler hasar skorunda azalma sağladı. Sonuç: Araştırmamız AP’nin parasetamol-uyarımlı renal hasarı engellediğini gösteren ilk rapordur. AP, yüksek doz parasetamol kaynaklı renal hasarın tedavisinde kullanılabilecek alternatif bir seçenek olabilir.

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Cite This Article

Bıçakçı, N., Bıçakçı, S., Karaboğa, İ. (2026). Nephroprotective Effect of Apilarnil in Acetaminophen-Induced Acute Kidney Injury Model. İstanbul Gelişim Üniversitesi Sağlık Bilimleri Dergisi, Sayı: 30, 399–410. https://doi.org/10.38079/igusabder.1643639

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References (40)

  1. Budnitz DS, Lovegrove MC, Crosby AE. Emergency department visits for overdoses of acetaminophen-containing products. American Journal of Preventive Medicine. 2011;40(6):585-592.
  2. Singh DP, Mani D. Protective effect of Triphala Rasayana against paracetamol-induced hepato–renal toxicity in mice. Journal of Ayurveda and Integrative Medicine. 2015;6(3):181.
  3. Çoban FK, İnce S, Demirel HH, İslam İ, Aytuğ H. Acetaminophen-induced nephrotoxicity: suppression of apoptosis and endoplasmic reticulum stress using boric acid. Biological Trace Element Research. 2023;201(1):242-249.
  4. Lewis RK, Paloucek FP. Assessment and treatment of acetaminophen. Clin Pharm. 1991;10:765-774.
  5. Oksuz E, Yasar S, Erten R, Arihan O, Oto G. Comparison of effects of high and low dose paracetamol treatment and toxicity on brain and liver in rats. Northern Clinics of İstanbul. 2020;7(6).
  6. Chidiac AS, Buckley NA, Noghrehchi F, Cairns R. Paracetamol (acetaminophen) overdose and hepatotoxicity: mechanism, treatment, prevention measures, and estimates of burden of disease. Expert Opinion on Drug Metabolism & Toxicology. 2023;19(5):297-317.
  7. Khan Z, Abumedian M, Ibekwe M, Musa K, Mlawa G. Acute renal impairment in patients due to paracetamol overdose in the absence of hepatic impairment. Cureus. 2021;13(12).
  8. 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. Biological Trace Element Research. 2023:1-10.
  9. Burcham PC. Target-organ toxicity: liver and kidney. An Introduction to Toxicology. 2014:151-187.
  10. Hazai E, Vereczkey L, Monostory K. Reduction of toxic metabolite formation of acetaminophen. Biochemical and Biophysical Research Communications. 2002;291(4):1089-1094.
  11. Gharishvandi F, Kazerouni F, Ghanei E, Rahimipour A, Nasiri M. Comparative assessment of neutrophil gelatinase-associated lipocalin (NGAL) and cystatin C as early biomarkers for early detection of renal failure in patients with hypertension. Iranian Biomedical Journal. 2015;19(2):76.
  12. Dua TK, Palai S, Roy A, Paul P. Protective effect of probiotics against acetaminophen induced nephrotoxicity. Molecular Biology Reports. 2022;49(8):8139-8143.
  13. Kanchanasurakit S, Arsu A, Siriplabpla W, Duangjai A, Saokaew S. Acetaminophen use and risk of renal impairment: A systematic review and meta-analysis. Kidney Research and Clinical Practice. 2020;39(1):81.
  14. Park WY. Controversies in acetaminophen nephrotoxicity. Kidney Research and Clinical Practice. 2020;39(1):4.
  15. Somani SM, Husain K, Whitworth C, Trammell GL, Malafa M, Rybak LP. Dose‐dependent protection by lipoic acid against cisplatin‐induced nephrotoxicity in rats: antioxidant defense system. Pharmacology & Toxicology. 2000;86(5):234-241.
  16. Wang X, Wu Q, Liu A, et al. Paracetamol: overdose-induced oxidative stress toxicity, metabolism, and protective effects of various compounds in vivo and in vitro. Drug metabolism reviews. 2017;49(4):395-437.
  17. El-Boshy M, BaSalamah MA, Ahmad J, et al. Vitamin D protects against oxidative stress, inflammation and hepatorenal damage induced by acute paracetamol toxicity in rat. Free Radical Biology and Medicine. 2019;141:310-321.
  18. Ghosh J, Das J, Manna P, Sil PC. Acetaminophen induced renal injury via oxidative stress and TNF-α production: therapeutic potential of arjunolic acid. Toxicology. 2010;268(1-2):8-18.
  19. Inci H, Izol E, Yilmaz MA, Ilkaya M, Bingöl Z, Gülçin I. Comprehensive phytochemical content by LC/MS/MS and anticholinergic, antiglaucoma, antiepilepsy, and antioxidant activity of apilarnil (Drone Larvae). Chemistry & Biodiversity. 2023;20(10):e202300654.
  20. Elashal MH, Abd El-Wahed AA, Mohamed MA, et al. Apilarnil ameliorates Bisphenol A-induced testicular toxicity in adult male rats via improving antioxidant potency and PCNA expression. Reproductive Toxicology. 2024;125:108570.
  21. Doğanyiğit Z, Okan A, Kaymak E, Pandır D, Silici S. Investigation of protective effects of apilarnil against lipopolysaccharide induced liver injury in rats via TLR 4/HMGB-1/NF-κB pathway. Biomedicine & Pharmacotherapy. 2020;125:109967.
  22. Gokkaya EO, Yesilot S, Ozgocmen M, Aslankoc R, Aydin Acar C. Protective effects of resveratrol and avocado oil against paracetamol-induced hepatotoxicity in rats. Drug and Chemical Toxicology. 2022;45(5):2131-2139.
  23. Ban KY, Nam GY, Kim D, Oh YS, Jun HS. Prevention of LPS-Induced acute kidney injury in mice by Bavachin and its potential mechanisms. Antioxidants. 2022;11(11):2096.
  24. Carter JH, Douglass LE, Deddens JA, et al. Pak-1 expression increases with progression of colorectal carcinomas to metastasis. Clinical Cancer Research. 2004;10(10):3448-3456.
  25. Hamamci M, Doganyigit Z, Silici S, et al. Apilarnil: a novel neuroprotective candidate. Acta Neurologica Taiwanica. 2020;29(2):33-45.
  26. Stollings JL, Wheeler AP, Rice TW. Incidence and characterization of acute kidney injury after acetaminophen overdose. Journal of Critical Care. 2016;35:191-194.
  27. Zhang X, Long F, Li R, et al. Tanshinone IIA prevents acetaminophen‐induced nephrotoxicity through the activation of the Nrf2‐Mrp2/4 pathway in mice. Environmental Toxicology. 2022;37(7):1618-1628.
  28. 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. Scientia Pharmaceutica. 2017;85(1):4.
  29. Nouioura G, Kettani T, Tourabi M, et al. The protective potential of Petroselinum crispum (Mill.) Fuss. on paracetamol-induced hepatio-renal toxicity and antiproteinuric effect: A biochemical, hematological, and histopathological study. Medicina. 2023;59(10):1814.
  30. Sohn SH, Lee EY, Lee JH, et al. Screening of herbal medicines for recovery of acetaminophen-induced nephrotoxicity. Environmental Toxicology and Pharmacology. 2009;27(2):225-230.
  31. İlbey YÖ, Ozbek E, Cekmen M, et al. Melatonin prevents acetaminophen-induced nephrotoxicity in rats. International Urology and Nephrology. 2009;41:695-702.
  32. Canayakin D, Bayir Y, Kilic Baygutalp N, et al. Paracetamol-induced nephrotoxicity and oxidative stress in rats: the protective role of Nigella sativa. Pharmaceutical Biology. 2016;54(10):2082-2091.
  33. Baponwa O, Amang A, Mezui C, et al. Antioxidant mechanism of renal and hepatic failure prevention related to paracetamol overdose by the aqueous extract of Amblygonocarpus andongensis stem bark. BioMed Research International. 2022;2022(1):1846558.
  34. Akgun E, Boyacioglu M, Kum S. The potential protective role of folic acid against acetaminophen-induced hepatotoxicity and nephrotoxicity in rats. Experimental Animals. 2021;70(1):54-62.
  35. Mohammed SA, Eldeeb HM, Mohammed HA, et al. Roles of Suaeda vermiculata aqueous-ethanolic extract, its subsequent fractions, and the isolated compounds in hepatoprotection against paracetamol-induced toxicity as compared to silymarin. Oxid Med Cell Longev. 2021:6174897.2021.
  36. Ahmad B, Muhammad Yousafzai A, Maria H, et al. Curative effects of Dianthus orientalis against paracetamol triggered oxidative stress, hepatic and renal injuries in rabbit as an experimental model. Separations. 2023;10(3):182.
  37. Abd El‐Wahed AA, Khalifa SA, Aldahmash B, et al. Exploring the chemical constituents and nutritive potential of bee drone (apilarnil): emphasis on antioxidant properties. Chemistry & Biodiversity. 2024:e202400085.
  38. Doğanyiğit Z, Köklü B, Uner A, Okan A, Kaymak E, Silici S. The effect of apilarnil on the autophagia against lipolysaccarite-based sepsis in liver. New Trends in Medicine Sciences. 2020;1(2):84-89.
  39. Ozatik FY, Teksen Y, Kadioglu E, Ozatik O, Bayat Z. Effects of hydrogen sulfide on acetaminophen-induced acute renal toxicity in rats. International Urology and Nephrology. 2019;51:745-754.
  40. Inandiklioglu N, Doganyigit Z, Okan A, Kaymak E, Silici S. Nephroprotective effect of apilarnil in lipopolysaccharide-induced sepsis through TLR4/NF-κB signaling pathway. Life Sciences. 2021;284:119875.