Enrofloksasinin Neden Olduğu Karaciğer Hasarında Selenyumun İyileştirici Rolü: Deney Sıçanları Üzerine Bir Çalışma

Öz

Bu çalışmanın amacı, selenyumun enrofloksasinin neden olduğu karaciğer hasarına karşı oksidatif stres, inflamasyon ve otofaji yolakları aracılığıyla sağladığı koruyucu etkileri araştırmaktı. Deney modelinde sıçanlar dört gruba ayrıldı: kontrol grubu (7 gün boyunca oral gavaj ve intraperitoneal (i.p.) enjeksiyon yoluyla fizyolojik salin verildi); selenyum (1 mg/kg, oral, 7 gün); enrofloksasin (150 mg/kg, i.p., 7 gün); ve enrofloksasin (150 mg/kg, i.p., 7 gün) + selenyum (1 mg/kg, oral, 7 gün). Karaciğer dokularında, malondialdehit (MDA), indirgenmiş glutatyon (GSH), süperoksit dismutaz (SOD), katalaz (CAT) ve glutatyon peroksidaz (GPx) dahil olmak üzere oksidatif stres belirteçleri ölçüldü. Ek olarak, enflamatuar ve otofajik yanıtları değerlendirmek için nükleer faktör kappa B (NF-κB), interlökin-1 beta (IL-1β), tümör nekroz faktörü-alfa (TNF-α) ve Beclin-1 ekspresyon düzeyleri analiz edildi. Enrofloksasin uygulaması, artmış MDA düzeyleriyle kanıtlandığı üzere lipit peroksidasyonunu artırmış ve GSH düzeylerini SOD, CAT ve GPx aktiviteleriyle birlikte önemli ölçüde azaltmıştır. Dahası, artmış NF-κB, IL-1β ve TNF-α düzeyleri enflamatuar yolakların aktivasyonunu gösterirken, artmış Beclin-1 ekspresyonu otofajinin uyarılmasını işaret etmiştir. Selenyum takviyesi, MDA düzeylerini düşürdü, GSH içeriğini ve antioksidan enzim aktivitelerini artırdı ve NF-κB, IL-1β, TNF-α ve Beclin-1 ekspresyonunu baskılayarak bu değişiklikleri önemli ölçüde iyileştirdi.Sonuç olarak, selenyum, lipit peroksidasyonunu azaltarak, antioksidan savunma sistemlerini güçlendirerek ve enflamatuar ve otofajik tepkileri düzenleyerek enrofloksasinin neden olduğu karaciğer hasarına karşı karaciğer koruyucu etkiler göstermektedir.

Anahtar Kelimeler

• Enrofloksasin
• selenyum
• hepatotoksisite
• oksidatif stres
• otofaji

Ameliorative Role of Selenium in Enrofloxacin-Induced Liver Damage: An Experimental Rat Study

Öz

ABSTRACT The present study aimed to investigate the protective effects of selenium (SE) against enrofloxacin (ENRO) induced liver damage through oxidative stress, inflammation, and autophagy pathways. Rats were divided into four groups: control (received physiological saline via oral gavage and intraperitoneal (i.p.) injection for 7 days); selenium (1 mg/kg, oral, 7 days); enrofloxacin (150 mg/kg, i.p., 7 days); and enrofloxacin (150 mg/kg, i.p., 7 days) + selenium (1 mg/kg, oral, 7 days). In liver tissues, oxidative stress markers including malondialdehyde (MDA), reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) were measured. Additionally, nuclear factor kappa B (NF-κB), interleukin-1 beta (IL-1β), tumor necrosis factor-alpha (TNF-α), and Beclin-1 expression were analyzed to evaluate inflammatory and autophagic responses ENRO administration increased NF-κB, IL-1β, TNF-α, and Beclin-1 expression together with elevated MDA levels, while decreasing GSH levels and SOD, CAT, and GPx activities. These alterations indicate increased lipid peroxidation, inflammation, and autophagy. These findings indicate that ENRO disrupts antioxidant defense systems and promotes inflammatory and autophagy-related responses in liver tissue. SE supplementation reduced MDA levels, enhanced GSH levels and antioxidant enzyme activities, and significantly ameliorated these alterations by suppressing NF-κB, IL-1β, TNF-α, and Beclin-1 expression. In conclusion, SE was found to exert hepatoprotective effects against ENRO induced liver injury by reducing lipid peroxidation, strengthening antioxidant defense systems, and regulating inflammatory and autophagic responses.

Anahtar Kelimeler

• Enrofloxacin
• hepatotoxicity
• inflammation
• oxidative stress
• selenium

Destekleyen Kurum

Bingol University

Etik Beyan

Ethical approval was obtained from the Bingol University Animal Experiments Local Ethics Committee (Date: 20.06.2025, Approval No: 2500002126).

Kaynakça

1. 1. Trouchon T, Lefebvre S. A Review of Enrofloxacin for Veterinary Use. Open J Vet Med. 2016;6(2):40-58.
2. 2. Luan Y, Zhao J, Han H, Shen J, Tang S, Cheng L. Toxicologic effect and transcriptome analysis for short-term orally dosed enrofloxacin combined with two veterinary antimicrobials on rat liver. Ecotoxicol Environ Saf. 2021;220:112398.
3. 3. Al-Taai NA, AL_Bayati HHK, Hdree DH, Abdullah BA. Physiological and histopathological assessment of the liver and kidney of Rat following administration of a acetaminophen and enrofloxacine. Tikrit J Vet Sci. 2023;2(1):33-47.
4. 4. Wei XL, Xu YC, Tan XY, et al. Enrofloxacin (ENR) exposure induces lipotoxicity by promoting mitochondrial fragmentation via dephosphorylation of DRP1 at S627 site. Chemosphere. 2023;340:139892.
5. 5. Guo X, Li W, An R, Huang M, Yu Z. Composite ammonium glycyrrhizin has hepatoprotective effects in chicken hepatocytes with lipopolysaccharide/enrofloxacin-induced injury. Exp Ther Med. 2020;20(5):52.
6. 6. Küçükler S, Çomaklı S, Özdemir S, et al. Investigating the Effects of Carvacrol in İsoproterenol-İnduced Myocardial İnjury: Role of H-FABP and Gal-3/TLR4/MYD88/NF-κB Signaling Pathway Modulation. Bratisl Med J. 2025;126(11):2954-2970.
7. 7. Poljsak B, Šuput D, Milisav I. Achieving the Balance between ROS and Antioxidants: When to Use the Synthetic Antioxidants. Oxid Med Cell Longev. 2013;2013:956792.
8. 8. 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.

9. 9. Salminen A, Kaarniranta K, Kauppinen A. Beclin 1 interactome controls the crosstalk between apoptosis, autophagy and inflammasome activation: Impact on the aging process. Ageing Res Rev. 2013;12(2):520-534.
10. 10. Wallenberg M, Misra S, Björnstedt M. Selenium cytotoxicity in cancer. Basic Clin Pharmacol Toxicol. 2014;114(5):377-386.
11. 11. Bai S, Zhang M, Tang S, et al. Effects and Impact of Selenium on Human Health, A Review. Molecules. 2024;30(1):50.
12. 12. Liu C, Chen K, Xu Z, et al. Potential Applications and Risks of Supranutritional Selenium Supplementation in Metabolic Dysfunction-Associated Steatotic Liver Disease: A Critical Review. Nutrients. 2025;17(15):2484.
13. 13. Bai K, Hong B, He J, Huang W. Antioxidant Capacity and Hepatoprotective Role of Chitosan-Stabilized Selenium Nanoparticles in Concanavalin A-Induced Liver Injury in Mice. Nutrients. 2020;12(3):857.
14. 14. Altunkaya M, Abuşoğlu G, Ozturk B. Investigation of the protective effect of selenium supplementation on renal function in cisplatin-administered rats. Cukurova Med J. 2024;49(2):304-313.
15. 15. Yi H, Shin MJ, Cho SM, et al. Nonlinear toxicokinetics of enrofloxacin in rats. Arch Pharm Res. 2010;33(11):1851-1857.
16. 16. Placer ZA, Cushman LL, Johnson BC. Estimation of product of lipid peroxidation (malonyl dialdehyde) in biochemical systems. Anal Biochem. 1966;16(2):359-364.
17. 17. Aebi H. Catalase in vitro. Methods Enzymol. 1984;105:121-126.
18. 18. Sun Y, Oberley LW, Li Y. A simple method for clinical assay of superoxide dismutase. Clin Chem. 1988;34(3):497-500.
19. 19. Lawrence RA, Burk RF. Glutathione peroxidase activity in selenium-deficient rat liver. Biochem Biophys Res Commun. 1976;71(4):952-958.
20. 20. Sedlak J, Lindsay RH. Estimation of total, protein-bound, and nonprotein sulfhydryl groups in tissue with Ellman’s reagent. Anal Biochem. 1968;25(1):192-205.
21. 21. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951;193(1):265-275.
22. 22. Livak KJ, Schmittgen TD. Analysis of Relative Gene Expression Data Using Real-Time Quantitative PCR and the 2−ΔΔCT Method. Methods. 2001;25(4):402-408.
23. 23. Xu YC, Zheng H, Guo JC, et al. Effects of Different Dietary Zinc (Zn) Sources on Growth Performance, Zn Metabolism, and Intestinal Health of Grass Carp. Antioxidants. 2023;12(9):1664.
24. 24. Luan J, Yu M, Gu Q, et al. Fatty acid synthase inhibition improves hypertension-induced erectile dysfunction by suppressing oxidative stress and NLRP3 inflammasome-dependent pyroptosis through activating the Nrf2/HO-1 pathway. Front Immunol. 2025;15.
25. 25. Salminen A, Kaarniranta K, Kauppinen A. Beclin 1 interactome controls the crosstalk between apoptosis, autophagy and inflammasome activation: impact on the aging process. Ageing Res Rev. 2013;12(2):520-534.
26. 26. Liu C, Chen K, Xu Z, et al. Potential Applications and Risks of Supranutritional Selenium Supplementation in Metabolic Dysfunction-Associated Steatotic Liver Disease: A Critical Review. Nutrients. 2025;17(15):2484.
27. 27. Bai K, Hong B, He J, Huang W. Antioxidant Capacity and Hepatoprotective Role of Chitosan-Stabilized Selenium Nanoparticles in Concanavalin A-Induced Liver Injury in Mice. Nutrients. 2020;12(3):857.