DEKSKETOPROFEN TROMETAMOLÜN SIÇAN BÖBREĞİ ÜZERİNDEKİ TOKSİK ETKİSİNE KARŞI C VİTAMİNİN KORUYUCU VE ÖNLEYİCİ ETKİSİNİN ARAŞTIRILMASI

Yıl 2025, Cilt: 14 Sayı: 2, 217 - 225, 24.12.2025

Ender Erdoğan , Özge Kandemir , Nurhan Akaras , Hasan Şimşek , Fatih Mehmet Kandemir

https://doi.org/10.31196/huvfd.1748738

Öz

Günümüzde birçok ağrı kesici kullanılmaktadır. Bunların önemli bir kısmı nonsteroid antiinflamatuar ilaçlardır (NSAİİ). Deksketoprofen trometamol (DEX), NSAİİ grubundan bir ağrı kesicidir. Sık ve yüksek doz kullanımı böbrekler üzerinde toksik etkilere sahiptir. C vitamini (Vit C) güçlü bir antioksidandır. Bu çalışmada, Vit C’ nin DEX' in böbrek toksisitesine karşı koruyucu ve önleyici etkileri araştırılmıştır. Mevcut çalışmada, böbrek toksisitesine, apoptoza ve lipid peroksidasyonuna neden olan biyobelirteçler değerlendirilmiştir. DEX grubunda, kontrol grubuyla karşılaştırıldığında; Üre, kreatinin, malondialdehit (MDA), interlökin-17A (IL-17A), nükleer faktör kappa-B (NF-κB), tümör nekroz faktörü-α (TNF-α), kaspaz-3, Bcl-2 ile ilişkili X proteini (Bax) ve böbrek hasarı molekülü-1 (KIM-1) değerleri daha yüksek, glutatyon (GSH), süperoksit dismutaz (SOD), katalaz (CAT), glutatyon peroksidaz (GPx), B hücreli lenfoma-2 (Bcl-2) ve aquaporin-2 (AQP-2) değerleri ise daha düşük bulundu. DEX+C Vitamini grubu DEX grubuyla karşılaştırıldığında üre, kreatinin, MDA, IL-17A, NF-κB, TNF-α, kaspaz-3, Bax ve KIM-1 değerleri daha düşük bulunurken, GSH, SOD, CAT, GPx, Bax ve AQP-2 değerleri daha yüksek bulundu. Kontrol grubuyla karşılaştırıldığında, DEX grubunda renal toksisite, apoptozis ve lipid peroksidasyon biyobelirteçlerinde artışlar gözlenirken, DEX+C Vitamini grubunda tam tersi sonuçlar gözlendi. Bu sonuçlar C Vitamininin DEX nefrotoksisitesine karşı koruyucu olduğunu gösterdi.

Anahtar Kelimeler

Apoptozis , Deksketoprofen trometamol , Nefrotoksisite , Oksidatif stres , C vitamini

Investigation of The Protective and Preventive Effect of Vitamin C Against the Toxic Effect of Dexketoprofen Trometamol on Rat Kidney

Öz

There are many painkillers used today. A significant portion of these are nonsteroidal anti-inflammatory drugs (NSAIDs). Dexketoprofen trometamol (DEX) is an analgesic drug from the NSAID group. Frequent and high-dose use has toxic effects on the kidneys. Vitamin C (Vit C) is a powerful antioxidant. The current study investigated the protective and preventive effects of Vit C against the kidney toxicity of DEX. In this study, biomarkers associated with kidney toxicity, apoptosis and lipid peroxidation were evaluated. In the DEX group, compared to the control group; Urea, creatinine, malondialdehyde (MDA), interleukin-17A (IL-17A), nuclear factor kappa-B (NF-κB), tumor necrosis factor-α (TNF-α), caspase-3, Bcl-2-associated X protein (Bax) and kidney injury molecule-1 (KIM-1) values were higher, while glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), B cell lymphoma-2 (Bcl-2) and aquaporin-2 (AQP-2) values were lower. When the DEX+Vit C group was compared with the DEX group, urea, creatinine, MDA, IL-17A, NF-κB, TNF-α, caspase-3, Bax and KIM-1 values were found lower, while GSH, SOD, CAT, GPx, Bax and AQP-2 values were found higher. Compared to the control group, the DEX group showed increases in biomarkers of renal toxicity, apoptosis, and lipid peroxidation, while the opposite results were observed in the DEX+Vit C group. These results demonstrated that Vit C protects against DEX nephrotoxicity.

Anahtar Kelimeler

Apoptosis , Dexketoprofen trometamol , Nephrotoxicity , Oxidative stress , Vitamin C.

Kaynakça

• Aebi H, 1984: Catalase in vitro. Methods Enzymol, 105, 121-126.
• Arise R, Malomo S, 2009: Effects of ivermectin and albendazole on some liver and kidney function indices in rats. Afr J Biochem Res, 3(5), 190-197.
• Ayyildiz M, Coskun S, Yildirim M, Agar E, 2007: The effects of ascorbic acid on penicillin-induced epileptiform activity in rats. Epilepsia, 48(7), 1388-1395.
• Barbanoj Rodríguez MJ, Antonijoan Arbós RM, Rico Amaro S, 2008: Dexketoprofen trometamol: clinical evidence supporting its role as a painkiller. Expert Rev Neurother, 8(11), 1625-1640.
• Bindu S, Mazumder S, Bandyopadhyay U, 2020: Non-steroidal anti-inflammatory drugs (NSAIDs) and organ damage: A current perspective. Biochem Pharmacol, 180, 114147.
• Burns J, 1957: Missing step in man, monkey and guinea pig required for the biosynthesis of L-ascorbic acid. Nature, 180(4585), 553-553.
• Carr AC, Maggini S, 2017: Vitamin C and immune function. Nutrients, 9(11), 1211.
• Chakraborthy A, Ramani P, Sherlin HJ, Premkumar P, Natesan A, 2014: Antioxidant and pro-oxidant activity of Vitamin C in oral environment. Indian J Dent Res, 25(4), 499-504.
• Chtourou Y, Aouey B, Aroui S, Kebieche M, Fetoui H, 2016: Anti-apoptotic and anti-inflammatory effects of naringin on cisplatin-induced renal injury in the rat. Chem Biol Interact, 243, 1-9.
• Conaghan PG, 2012: A turbulent decade for NSAIDs: update on current concepts of classification, epidemiology, comparative efficacy, and toxicity. Rheumatol Int, 32, 1491-1502.
• Di Renzo L, De Lorenzo A, Fontanari M, Gualtieri P, Monsignore D, Schifano G, Alfano V, Marchetti M, SIERR, 2022: Immunonutrients involved in the regulation of the inflammatory and oxidative processes: implication for gamete competence. J Assist Reprod Genet, 39(4), 817-846.
• Erdoğan E, Kandemir O, Akaras N, Şimşek H, Kandemir FM, 2025: Folik Asidin İvermektin Kaynaklı Böbrek Toksisitesine Karşı Koruyucu ve Önleyici Rolü. F U Vet J Health Sci, 39(2), 113-121.
• Ertürk Ö, Değirmenci A, Yurdakul Ertürk E, Atlı Şekeroğlu Z, Çol Ayvaz M, Kontaş Yedier S, 2021: Antimicrobial, antioxidant and cytotoxic activities of some analgesic or anti-inflammatory drugs. Biologia, 76(8), 2365-2379.
• Guijarro C, Egido J, 2001: Transcription factor-κB (NF-κB) and renal disease. Kidney Int, 59.2: 415-424.
• Herrero JF, Romero-Sandoval EA, Gaitan G, Mazario J, 2003: Antinociception and the new COX inhibitors: research approaches and clinical perspectives. CNS Drug Rev, 9(3), 227-252.
• Inal S, Kabay S, Cayci MK, Kuru HI, Altikat S, Akkas G, Deger A, 2014: Comparison of the effects of dexketoprofen trometamol, meloxicam and diclofenac sodium on fibular fracture healing, kidney and liver: an experimental rat model. Injury, 45(3), 494-500.
• Kankılıç NA, Şimşek H, Akaras N, Gür C, Küçükler S, İleritürk M, Gencer S, Kandemir FM 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, 190, 114791.
• Karović M, Nikolić M, Nedeljković N, Vesović M, Nikolić M, Anđić M, Lazarević N, Jakovljević V, Nedeljković J, Đaković S, 2025: From Chemistry to Pharmacology: Exploring the Anti-Inflammatory and Antioxidant Potential of Novel Dexketoprofen Amide Derivatives. Antioxidants, 14(7), 796.
• Kılıc M, Tuylu, BA 2020: An in vitro investigation of genotoxic effects of dexketoprofen trometamol on healthy human lymphocytes. Drug Chem Toxicol, 43(2), 174-181.
• Koksal E, Ustun YB, Bilgin S, Aksoy A, Das YK, Yarim M, Ozkan, F, Kaya C, Dost B, 2022: The effects of dexketoprofen on renal ischemia-reperfusion injury: an experimental study. Braz J Anesthesiol, 72(3), 365-371.
• Lawrence RA, Burk RF, 1976: Glutathione peroxidase activity in selenium-deficient rat liver. Biochem Biophys Res Commun, 71(4), 952-958.
• Livak KJ, Schmittgen TD, 2001: Analysis of relative gene expression data using real-time quantitative PCR and the 2− ΔΔCT method. Methods, 25(4), 402-408.
• Lowry OH, Rosebrough NJ, Farr AL, Randall RJ, 1951: Protein measurement with the Folin phenol reagent. J Biol Chem, 193(1), 265–275.
• Nishikimi M, Fukuyama R, Minoshima S, Shimizu N, Yagi K, 1994: Cloning and chromosomal mapping of the human nonfunctional gene for L-gulono-gamma-lactone oxidase, the enzyme for L-ascorbic acid biosynthesis missing in man. J Biol Chem, 269(18), 13685-13688.
• Placer ZA, Cushman LL, Johnson BC, 1966: Estimation of product of lipid peroxidation (malonyl dialdehyde) in biochemical systems. Anal Biochem, 16(2), 359-364.
• Pullar JM, Carr AC, Vissers M, 2017: The roles of vitamin C in skin health. Nutrients, 9(8), 866.
• Rodriguez MJB, Arbós RMA, Amaro SR, 2008: Dexketoprofeno-trometamina: evidencia clínica apoya su eficacia como analgésico. Expert Rev Neurother, 8(11), 1625-1640.
• Saha D, 2014: Role of free radicals, oxidative stress and xenobiotics in carcinogenesis by environmental pollutants. Avances en Biomedicina, 3(2), 6.
• Salazar JH, 2014: Overview of urea and creatinine. Lab Med, 45(1), e19-e20.
• Sedlak J, Lindsay RH, 1968: Estimation of total, protein-bound, and nonprotein sulfhydryl groups in tissue with Ellman's reagent. Anal Biochem, 25, 192-205.
• Shigenaga MK, Hagen TM, Ames BN, 1994: Oxidative damage and mitochondrial decay in aging. Proc Natl Acad Sci U S A, 91(23), 10771-10778.
• Smaili S, Hsu YT, Carvalho A, Rosenstock T, Sharpe J, Youle R, 2003: Mitochondria, calcium and pro-apoptotic proteins as mediators in cell death signaling. Braz J Med Biol Res, 36, 183-190.
• Sun Y, Oberley LW, Li Y, 1988: A simple method for clinical assay of superoxide dismutase. Clin Chem, 34(3), 497-500.
• Şimşek H, Küçükler S, Gür C, Akaras N, Kandemir FM, 2023: Protective effects of sinapic acid against lead acetate-induced nephrotoxicity: a multi-biomarker approach. Environ Sci Pollut Res Int, 30(45), 101208-101222.
• Tekeli AE, Yağmurdur H, Take DE, Dikmen B, 2017: Histological and electron micr examination of the effect of D Trometamol on liver in rats. Med Sci, 21(88), 329-335.
• Yilmaz S, Gur C, Kucukler S, Akaras N, Kandemir FM, 2024: 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, 27(4), 485.