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Humic Acid Alleviates Lipopolysaccharide-Induced Acute Kidney Injury by Regulating TNF-α Expression

Yıl 2025, Cilt: 14 Sayı: 3, 938 - 946, 25.09.2025

Öz

Sepsis-induced acute kidney injury (AKI) is a clinical condition with a high mortality rate despite advances in health. This study aimed to investigate the potential protective effect of HA in the LPS-induced rat AKI model. A total of 24 adult male Wistar albino rats were used in the study. The rats were randomly divided into three groups: (1) Control group, (2) LPS group and (3) HA+LPS group. Lipopolysaccharide (LPS) was administered at a dose of 5 mg/kg to the LPS group, while humic acid (HA) was administered at a dose of 50 mg/kg for three days before LPS injection to the HA+LPS group. Histopathological changes in the renal tissues were evaluated by hematoxylin-eosin (H&E) staining method. In addition, tumor necrosis factor-alpha (TNF-α) expression levels were examined by immunohistochemical analyses. Malondialdehyde (MDA), total antioxidant capacity (TAS), total oxidant capacity (TOS), superoxide dismutase (SOD), glutathione peroxidase (GPx) as oxidative stress markers were analyzed. Parameters such as blood urea nitrogen (BUN), creatinine (CREA), lactate dehydrogenase (LDH), total protein (TP), albumin, uric acid were analyzed in serum samples. Our findings show that HA treatment applied in rat sepsis model reduces renal tubular damage and decreases TNF-α expression. In conclusion, HA may improve renal functions by regulating inflammation in LPS-induced AKI model.

Kaynakça

  • 1. Okan, A., Doğanyiğit, Z., Yilmaz, S., Uçar, S., Arikan Söylemez, E.S., & Attar, R. (2023). “Evaluation of the protective role of resveratrol against sepsis caused by LPS via TLR4/NF‐κB/TNF‐α signaling pathways: Experimental study”. Cell Biochemistry and Function, 41(4), 423-433. https://doi.org/10.1002/cbf.3790
  • 2. Rello, J., Valenzuela-Sánchez, F., Ruiz-Rodriguez, M., & Moyano, S. (2017). “Sepsis: a review of advances in management”. Advances in Therapy, 34(11), 2393-2411. https://doi.org/10.1007/s12325-017-0622-8
  • 3. Santos, R.A.S., Sampaio, W.O., Alzamora, A.C., Motta-Santos, D., Alenina, N., Bader, M., et al. (2017). “The ACE2/angiotensin-(1–7)/MAS axis of the renin-angiotensin system: focus on angiotensin-(1–7)”. Physiological Reviews, 97(2), 505-553. https://doi.org/10.1152/physrev.00023.2016
  • 4. Zhao, J., Duan, Q., Dong, C., & Cui, J. (2022). “Cul4a attenuates LPS-induced acute kidney injury via blocking NF-κB signaling pathway in sepsis”. Journal of Medical Biochemistry, 41(1), 62-69. https://doi.org/10.5937/jomb0-33096
  • 5. Lee, S.A., Cozzi, M., Bush, E.L., & Rabb, H. (2018). “Distant organ dysfunction in acute kidney injury: a review”. American Journal of Kidney Diseases, 72(6), 846-856. https://doi.org/10.1053/j.ajkd.2018.03.028
  • 6. Molema, G., Zijlstra, J.G., van Meurs, M., & Kamps, J.A. (2022). “Renal microvascular endothelial cell responses in sepsis-induced acute kidney injury”. Nature Reviews Nephrology, 18(2), 95-112. https://doi.org/10.1038/s41581-021-00489-1
  • 7. Malek, M. (2018). “Brain consequences of acute kidney injury: Focusing on the hippocampus”. Kidney Research and Clinical Practice, 37(4), 315-322. https://doi.org/10.23876/j.krcp.18.0056
  • 8. Ronco, C., Bellasi, A., & Di Lullo, L. (2019). “Implication of acute kidney injury in heart failure”. Heart Failure Clinics, 15(4), 463-476. https://doi.org/10.1016/j.hfc.2019.05.002
  • 9. Tomsa, A.M., Alexa, A.L., Junie, M.L., Rachisan, A.L., & Ciumarnean, L. (2019). “Oxidative stress as a potential target in acute kidney injury”. PeerJ, 7, e8046. https://doi.org/10.7717/peerj.8046
  • 10. Hoste, E.A., Bagshaw, S.M., Bellomo, R., Cely, C.M., Colman, R., Cruz, D.N., et al. (2015). “Epidemiology of acute kidney injury in critically ill patients: the multinational AKI-EPI study”. Intensive Care Medicine, 41(8), 1411-1423. https://doi.org/10.1007/s00134-015-3934-7
  • 11. Cai, L., Rodgers, E., Schoenmann, N., & Raju, R.P. (2023). “Advances in rodent experimental models of sepsis”. International Journal of Molecular Sciences, 24(11), 9578. https://doi.org/10.3390/ijms24119578
  • 12. Karaboga, I., Okuyan, H.M., Dogan, S., Aycicek, S.O., & Cakiroglu, H. (2025). “Ebselen alleviates sepsis-induced acute kidney injury by regulating endoplasmic reticulum stress, apoptosis, and oxidative stress”. Veterinary Medicine and Science, 11(2), e70318. https://doi.org/10.1002/vms3.70318
  • 13. Shareef, M., & Kathem, H. (2022). “Gentiopicroside ameliorates lipopolysaccharide-induced acute kidney injury by inhibiting TLR4/NF-κB signaling in mice model”. Journal of Pharmaceutical Negative Results, 13(4), 135-145. https://doi.org/10.47750/pnr.2022.13.04.018
  • 14. Lu, Q.B., Du, Q., Wang, H.P., Tang, Z.H., Wang, Y.B., & Sun, H.J. (2020). “Salusin-β mediates tubular cell apoptosis in acute kidney injury: involvement of the PKC/ROS signaling pathway”. Redox Biology, 30, 101411. https://doi.org/10.1016/j.redox.2020.101411
  • 15. Yang, Y., Xu, J., Tu, J., Sun, Y., Zhang, C., Qiu, Z., et al. (2024). “Polygonum cuspidatum Sieb. et Zucc. extracts improve sepsis-associated acute kidney injury by inhibiting NF-κB-mediated inflammation and pyroptosis”. Journal of Ethnopharmacology, 319, 117101. https://doi.org/10.1016/j.jep.2024.117101
  • 16. Dennis, J.M., & Witting, P.K. (2017). “Protective role for antioxidants in acute kidney disease”. Nutrients, 9(7), 718. https://doi.org/10.3390/nu9070718
  • 17. Delanaye, P., White, C.A., Ebert, N., & Rule, A.D. (2020). “Assessing kidney function”. Chronic Kidney Disease, 37-54.
  • 18. Mortazavi, A., Hosseini, M., Beheshti, F., Hakimi, Z., Vaezi, G.H., & Pour Kargar, H.M. (2024). “The effect of carvacrol on IL-1β and nitric oxide levels on lipopolysaccharide-induced acute renal injury in male rats”. Journal of Chemical Health Risks, 14(1).
  • 19. Ozkan, A., Sen, H.M., Sehitoglu, I., Alacam, H., Guven, M., Aras, A.B., et al. (2015). “Neuroprotective effect of humic acid on focal cerebral ischemia injury: an experimental study in rats”. Inflammation, 38(1), 32-39. https://doi.org/10.1007/s10753-014-0003-x
  • 20. Gau, R.J., Yang, H.L., Chow, S.N., Suen, J.L., & Lu, F.J. (2000). “Humic acid suppresses the LPS-induced expression of cell-surface adhesion proteins through the inhibition of NF-κB activation”. Toxicology and Applied Pharmacology, 166(1), 59-67. https://doi.org/10.1006/taap.2000.8957
  • 21. Fouad, A.A., Qutub, H.O., & Al-Melhim, W.N. (2016). “Nephroprotection of punicalagin in rat model of endotoxemic acute kidney injury”. Toxicology Mechanisms and Methods, 26(7), 538-543. https://doi.org/10.3109/15376516.2016.1185065
  • 22. Niu, X., Wang, C., Li, H., & Chen, W. (2024). “Role of OPG/RANKL/RANK/TLR4 signaling pathway in sepsis-associated acute kidney injury”. BMC Nephrology, 25(1), 205. https://doi.org/10.1186/s12882-024-03725-7
  • 23. Carter, J.H., Douglass, L.E., Deddens, J.A., Colligan, B.M., Bhatt, T.R., Pemberton, J.O., et al. (2004). “Pak-1 expression increases with progression of colorectal carcinomas to metastasis”. Clinical Cancer Research, 10(10), 3448-3456. https://doi.org/10.1158/1078-0432.CCR-03-0373
  • 24. Shou, D.W., Li, Y.R., Xu, X.J., Dai, M.H., Zhang, W., Yang, X., et al. (2023). “Parthenolide attenuates sepsis-induced acute kidney injury in rats by reducing inflammation”. Evidence-Based Complementary and Alternative Medicine, 2023, 8759766. https://doi.org/10.1155/2023/8759766
  • 25. Tsantarliotou, M., Lavrentiadou, S., Psalla, D., Margaritis, I., Kritsepi, M., Zervos, I., et al. (2019). “Suppression of plasminogen activator inhibitor-1 (PAI-1) activity by crocin ameliorates lipopolysaccharide-induced thrombosis in rats”. Food and Chemical Toxicology, 125, 190-197. https://doi.org/10.1016/j.fct.2018.12.005
  • 26. Lee, S.J., Borsting, E., Declèves, A.E., Singh, P., & Cunard, R. (2012). “Podocytes express IL-6 and lipocalin 2/neutrophil gelatinase-associated lipocalin in lipopolysaccharide-induced acute glomerular injury”. Nephron Experimental Nephrology, 121(3-4), e86-e96. https://doi.org/10.1159/000345546
  • 27. Moreira, R.S., Irigoyen, M., Sanches, T.R., Volpini, R.A., Camara, N.O., Malheiros, D.M., et al. (2014). “Apolipoprotein AI mimetic peptide 4F attenuates kidney injury, heart injury, and endothelial dysfunction in sepsis”. American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, 307(5), R514-R524. https://doi.org/10.1152/ajpregu.00512.2013
  • 28. Silveira, M., Capcha, J., Sanches, T., Moreira, R., Garnica, M., Shimizu, M., et al. (2021). “Green propolis extract attenuates acute kidney injury and lung injury in a rat model of sepsis”. Scientific Reports, 11, 5925. https://doi.org/10.1038/s41598-021-85438-w
  • 29. Ozkan, A., Sen, H.M., Sehitoglu, I., Alacam, H., Guven, M., Aras, A.B., et al. (2015). “Neuroprotective effect of humic acid on focal cerebral ischemia injury: an experimental study in rats”. Inflammation, 38(1), 32-39. https://doi.org/10.1007/s10753-014-0003-x
  • 30. Khaled, H., & Fawy, H.A. (2011). “Effect of different levels of humic acids on the nutrient content, plant growth, and soil properties under conditions of salinity”. Soil and Water Research, 6(1), 21-29.
  • 31. Şehitoğlu, M.H., Öztopuz, Ö., Karaboğa, İ., Ovalı, M.A., & Uzun, M. (2022). “Humic acid has protective effect on gastric ulcer by alleviating inflammation in rats”. Cytology and Genetics, 56(1), 84-97. https://doi.org/10.3103/S0095452722010083
  • 32. Orlando, P.R., Tavares, H.G., de Souza Pereira, R.R., Silva, G., Carvalho, JdCL., Machado, A.R.T., et al. (2025). “Humic acid derived from agricultural biomass mitigates alveolar bone loss and modulates systemic inflammatory cytokines in rats with periodontitis”. Current Topics in Medicinal Chemistry, 25(5), 645-656. https://doi.org/10.2174/1568026625666230511121122
  • 33. Tekes, E., Ickin Gulen, M., Silan, C., & Guven Bagla, A. (2025). “Humic acid attenuates cisplatin-induced nephrotoxicity in rats”. Drug and Chemical Toxicology, 1-9. https://doi.org/10.1080/01480545.2025.2415084
  • 34. Williams, R. (2025). “COVID-19 humic/fulvic acid plus epigallocatechin gallate treatment: a retrospective chart review”. Cureus, 17(1). https://doi.org/10.7759/cureus.54087
  • 35. Hseu, Y.C., Kumar, K.S., Chen, C.S., Cho, H.J., Lin, S.W., Shen, P.C., et al. (2014). “Humic acid in drinking well water induces inflammation through reactive oxygen species generation and activation of NF-κB/AP-1 signaling pathways: a possible role in atherosclerosis”. Toxicology and Applied Pharmacology, 274(2), 249-262. https://doi.org/10.1016/j.taap.2013.11.017
  • 36. Piko, N., Bevc, S., Hojs, R., & Ekart, R. (2023). “The role of oxidative stress in kidney injury”. Antioxidants, 12(9), 1772. https://doi.org/10.3390/antiox12091772
  • 37. Akbas, A., Silan, C., Gulpinar, M.T., Sancak, E.B., Ozkanli, S.S., & Cakir, D.U. (2015). “Renoprotective effect of humic acid on renal ischemia-reperfusion injury: an experimental study in rats”. Inflammation, 38(5), 2042-2048. https://doi.org/10.1007/s10753-015-0182-2
  • 38. Hammoud, G.M., Nail, N.S., Abd El-Shafea, Y.M., & Salem, A.A. (2019). “Histopathological study on the protective effect of humic acid against aflatoxins induced-oxidative stress in rats”. International Journal of Advanced Research in Biological Sciences, 6(3), 111-127.
  • 39. Krstic, D., Tomic, N., Radosavljevic, B., Avramovic, N., Dragutinovic, V., Skodric, S.R., et al. (2016). “Biochemical markers of renal function”. Current Medicinal Chemistry, 23(19), 2018-2040. https://doi.org/10.2174/0929867323666160411120912
  • 40. Zanotti-Cavazzoni, S.L., & Goldfarb, R.D. (2009). “Animal models of sepsis”. Critical Care Clinics, 25(4), 703-719. https://doi.org/10.1016/j.ccc.2009.07.003

Humik Asit TNF-α İfadesini Düzenleyerek Lipopolisakkarit-uyarımlı Akut Böbrek Hasarını Hafifletir

Yıl 2025, Cilt: 14 Sayı: 3, 938 - 946, 25.09.2025

Öz

Sepsis-uyarımlı akut böbrek hasarı (ABH) sağlık alanındaki gelişmelere rağmen yüksek mortalite oranına sahip bir klinik tablodur. Bu çalışmada HA’nın LPS ile indüklenen sıçan ABH modelinde potansiyel koruyucu etkisinin incelenmesi amaçlanmıştır. Çalışmada toplam 24 adet erişkin erkek Wistar albino sıçan kullanıldı. Sıçanlar rastgele olarak üç gruba ayrıldı: (1) Kontrol grubu, (2) LPS grubu ve (3) HA+LPS grubu. LPS grubuna 5 mg/kg dozunda Lipopolisakkarit (LPS) uygulanırken, HA+LPS grubuna LPS enjeksiyonundan önceki üç gün boyunca 50 mg/kg dozunda Humik asit (HA) tedavisi uygulandı. Böbrek dokularındaki histopatolojik değişiklikler Hematoksilen-Eozin (H&E) boyama yöntemi ile değerlendirildi. Ayrıca, tümör nekroz faktörü-alfa (TNF-α) ekspresyon düzeyleri immünohistokimyasal analizlerle incelendi. Malondialdehit (MDA) total antioksidan kapasite (TAS), total oksidan kapasite (TOS), süperoksit dismutaz (SOD), Glutatyon peroksidaz (GPx) gibi oksidatif stres belirteçleri analiz edildi. Kan üre azotu (BUN), kreatinin (CREA), laktat dehidrogenaz (LDH), total protein (TP), albumin, ürik asit gibi parametreler serum numunelerinde analiz edildi. Bulgularımız, sıçan sepsis modelinde uygulanan HA tedavisinin renal tübüler hasarı azalttığını ve TNF-α ekspresyonunu düşürdüğünü göstermektedir. Sonuç olarak, HA, LPS-uyarımlı ABH modelinde inflamasyonu düzenleyerek renal fonksiyonları iyileştirebilir.

Etik Beyan

Bu çalışmanın tüm deney protokolleri Sakarya Üniversitesi Yerel Hayvan Etik Kurulu tarafından onaylandı (İzin numarası: 2025/45).

Kaynakça

  • 1. Okan, A., Doğanyiğit, Z., Yilmaz, S., Uçar, S., Arikan Söylemez, E.S., & Attar, R. (2023). “Evaluation of the protective role of resveratrol against sepsis caused by LPS via TLR4/NF‐κB/TNF‐α signaling pathways: Experimental study”. Cell Biochemistry and Function, 41(4), 423-433. https://doi.org/10.1002/cbf.3790
  • 2. Rello, J., Valenzuela-Sánchez, F., Ruiz-Rodriguez, M., & Moyano, S. (2017). “Sepsis: a review of advances in management”. Advances in Therapy, 34(11), 2393-2411. https://doi.org/10.1007/s12325-017-0622-8
  • 3. Santos, R.A.S., Sampaio, W.O., Alzamora, A.C., Motta-Santos, D., Alenina, N., Bader, M., et al. (2017). “The ACE2/angiotensin-(1–7)/MAS axis of the renin-angiotensin system: focus on angiotensin-(1–7)”. Physiological Reviews, 97(2), 505-553. https://doi.org/10.1152/physrev.00023.2016
  • 4. Zhao, J., Duan, Q., Dong, C., & Cui, J. (2022). “Cul4a attenuates LPS-induced acute kidney injury via blocking NF-κB signaling pathway in sepsis”. Journal of Medical Biochemistry, 41(1), 62-69. https://doi.org/10.5937/jomb0-33096
  • 5. Lee, S.A., Cozzi, M., Bush, E.L., & Rabb, H. (2018). “Distant organ dysfunction in acute kidney injury: a review”. American Journal of Kidney Diseases, 72(6), 846-856. https://doi.org/10.1053/j.ajkd.2018.03.028
  • 6. Molema, G., Zijlstra, J.G., van Meurs, M., & Kamps, J.A. (2022). “Renal microvascular endothelial cell responses in sepsis-induced acute kidney injury”. Nature Reviews Nephrology, 18(2), 95-112. https://doi.org/10.1038/s41581-021-00489-1
  • 7. Malek, M. (2018). “Brain consequences of acute kidney injury: Focusing on the hippocampus”. Kidney Research and Clinical Practice, 37(4), 315-322. https://doi.org/10.23876/j.krcp.18.0056
  • 8. Ronco, C., Bellasi, A., & Di Lullo, L. (2019). “Implication of acute kidney injury in heart failure”. Heart Failure Clinics, 15(4), 463-476. https://doi.org/10.1016/j.hfc.2019.05.002
  • 9. Tomsa, A.M., Alexa, A.L., Junie, M.L., Rachisan, A.L., & Ciumarnean, L. (2019). “Oxidative stress as a potential target in acute kidney injury”. PeerJ, 7, e8046. https://doi.org/10.7717/peerj.8046
  • 10. Hoste, E.A., Bagshaw, S.M., Bellomo, R., Cely, C.M., Colman, R., Cruz, D.N., et al. (2015). “Epidemiology of acute kidney injury in critically ill patients: the multinational AKI-EPI study”. Intensive Care Medicine, 41(8), 1411-1423. https://doi.org/10.1007/s00134-015-3934-7
  • 11. Cai, L., Rodgers, E., Schoenmann, N., & Raju, R.P. (2023). “Advances in rodent experimental models of sepsis”. International Journal of Molecular Sciences, 24(11), 9578. https://doi.org/10.3390/ijms24119578
  • 12. Karaboga, I., Okuyan, H.M., Dogan, S., Aycicek, S.O., & Cakiroglu, H. (2025). “Ebselen alleviates sepsis-induced acute kidney injury by regulating endoplasmic reticulum stress, apoptosis, and oxidative stress”. Veterinary Medicine and Science, 11(2), e70318. https://doi.org/10.1002/vms3.70318
  • 13. Shareef, M., & Kathem, H. (2022). “Gentiopicroside ameliorates lipopolysaccharide-induced acute kidney injury by inhibiting TLR4/NF-κB signaling in mice model”. Journal of Pharmaceutical Negative Results, 13(4), 135-145. https://doi.org/10.47750/pnr.2022.13.04.018
  • 14. Lu, Q.B., Du, Q., Wang, H.P., Tang, Z.H., Wang, Y.B., & Sun, H.J. (2020). “Salusin-β mediates tubular cell apoptosis in acute kidney injury: involvement of the PKC/ROS signaling pathway”. Redox Biology, 30, 101411. https://doi.org/10.1016/j.redox.2020.101411
  • 15. Yang, Y., Xu, J., Tu, J., Sun, Y., Zhang, C., Qiu, Z., et al. (2024). “Polygonum cuspidatum Sieb. et Zucc. extracts improve sepsis-associated acute kidney injury by inhibiting NF-κB-mediated inflammation and pyroptosis”. Journal of Ethnopharmacology, 319, 117101. https://doi.org/10.1016/j.jep.2024.117101
  • 16. Dennis, J.M., & Witting, P.K. (2017). “Protective role for antioxidants in acute kidney disease”. Nutrients, 9(7), 718. https://doi.org/10.3390/nu9070718
  • 17. Delanaye, P., White, C.A., Ebert, N., & Rule, A.D. (2020). “Assessing kidney function”. Chronic Kidney Disease, 37-54.
  • 18. Mortazavi, A., Hosseini, M., Beheshti, F., Hakimi, Z., Vaezi, G.H., & Pour Kargar, H.M. (2024). “The effect of carvacrol on IL-1β and nitric oxide levels on lipopolysaccharide-induced acute renal injury in male rats”. Journal of Chemical Health Risks, 14(1).
  • 19. Ozkan, A., Sen, H.M., Sehitoglu, I., Alacam, H., Guven, M., Aras, A.B., et al. (2015). “Neuroprotective effect of humic acid on focal cerebral ischemia injury: an experimental study in rats”. Inflammation, 38(1), 32-39. https://doi.org/10.1007/s10753-014-0003-x
  • 20. Gau, R.J., Yang, H.L., Chow, S.N., Suen, J.L., & Lu, F.J. (2000). “Humic acid suppresses the LPS-induced expression of cell-surface adhesion proteins through the inhibition of NF-κB activation”. Toxicology and Applied Pharmacology, 166(1), 59-67. https://doi.org/10.1006/taap.2000.8957
  • 21. Fouad, A.A., Qutub, H.O., & Al-Melhim, W.N. (2016). “Nephroprotection of punicalagin in rat model of endotoxemic acute kidney injury”. Toxicology Mechanisms and Methods, 26(7), 538-543. https://doi.org/10.3109/15376516.2016.1185065
  • 22. Niu, X., Wang, C., Li, H., & Chen, W. (2024). “Role of OPG/RANKL/RANK/TLR4 signaling pathway in sepsis-associated acute kidney injury”. BMC Nephrology, 25(1), 205. https://doi.org/10.1186/s12882-024-03725-7
  • 23. Carter, J.H., Douglass, L.E., Deddens, J.A., Colligan, B.M., Bhatt, T.R., Pemberton, J.O., et al. (2004). “Pak-1 expression increases with progression of colorectal carcinomas to metastasis”. Clinical Cancer Research, 10(10), 3448-3456. https://doi.org/10.1158/1078-0432.CCR-03-0373
  • 24. Shou, D.W., Li, Y.R., Xu, X.J., Dai, M.H., Zhang, W., Yang, X., et al. (2023). “Parthenolide attenuates sepsis-induced acute kidney injury in rats by reducing inflammation”. Evidence-Based Complementary and Alternative Medicine, 2023, 8759766. https://doi.org/10.1155/2023/8759766
  • 25. Tsantarliotou, M., Lavrentiadou, S., Psalla, D., Margaritis, I., Kritsepi, M., Zervos, I., et al. (2019). “Suppression of plasminogen activator inhibitor-1 (PAI-1) activity by crocin ameliorates lipopolysaccharide-induced thrombosis in rats”. Food and Chemical Toxicology, 125, 190-197. https://doi.org/10.1016/j.fct.2018.12.005
  • 26. Lee, S.J., Borsting, E., Declèves, A.E., Singh, P., & Cunard, R. (2012). “Podocytes express IL-6 and lipocalin 2/neutrophil gelatinase-associated lipocalin in lipopolysaccharide-induced acute glomerular injury”. Nephron Experimental Nephrology, 121(3-4), e86-e96. https://doi.org/10.1159/000345546
  • 27. Moreira, R.S., Irigoyen, M., Sanches, T.R., Volpini, R.A., Camara, N.O., Malheiros, D.M., et al. (2014). “Apolipoprotein AI mimetic peptide 4F attenuates kidney injury, heart injury, and endothelial dysfunction in sepsis”. American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, 307(5), R514-R524. https://doi.org/10.1152/ajpregu.00512.2013
  • 28. Silveira, M., Capcha, J., Sanches, T., Moreira, R., Garnica, M., Shimizu, M., et al. (2021). “Green propolis extract attenuates acute kidney injury and lung injury in a rat model of sepsis”. Scientific Reports, 11, 5925. https://doi.org/10.1038/s41598-021-85438-w
  • 29. Ozkan, A., Sen, H.M., Sehitoglu, I., Alacam, H., Guven, M., Aras, A.B., et al. (2015). “Neuroprotective effect of humic acid on focal cerebral ischemia injury: an experimental study in rats”. Inflammation, 38(1), 32-39. https://doi.org/10.1007/s10753-014-0003-x
  • 30. Khaled, H., & Fawy, H.A. (2011). “Effect of different levels of humic acids on the nutrient content, plant growth, and soil properties under conditions of salinity”. Soil and Water Research, 6(1), 21-29.
  • 31. Şehitoğlu, M.H., Öztopuz, Ö., Karaboğa, İ., Ovalı, M.A., & Uzun, M. (2022). “Humic acid has protective effect on gastric ulcer by alleviating inflammation in rats”. Cytology and Genetics, 56(1), 84-97. https://doi.org/10.3103/S0095452722010083
  • 32. Orlando, P.R., Tavares, H.G., de Souza Pereira, R.R., Silva, G., Carvalho, JdCL., Machado, A.R.T., et al. (2025). “Humic acid derived from agricultural biomass mitigates alveolar bone loss and modulates systemic inflammatory cytokines in rats with periodontitis”. Current Topics in Medicinal Chemistry, 25(5), 645-656. https://doi.org/10.2174/1568026625666230511121122
  • 33. Tekes, E., Ickin Gulen, M., Silan, C., & Guven Bagla, A. (2025). “Humic acid attenuates cisplatin-induced nephrotoxicity in rats”. Drug and Chemical Toxicology, 1-9. https://doi.org/10.1080/01480545.2025.2415084
  • 34. Williams, R. (2025). “COVID-19 humic/fulvic acid plus epigallocatechin gallate treatment: a retrospective chart review”. Cureus, 17(1). https://doi.org/10.7759/cureus.54087
  • 35. Hseu, Y.C., Kumar, K.S., Chen, C.S., Cho, H.J., Lin, S.W., Shen, P.C., et al. (2014). “Humic acid in drinking well water induces inflammation through reactive oxygen species generation and activation of NF-κB/AP-1 signaling pathways: a possible role in atherosclerosis”. Toxicology and Applied Pharmacology, 274(2), 249-262. https://doi.org/10.1016/j.taap.2013.11.017
  • 36. Piko, N., Bevc, S., Hojs, R., & Ekart, R. (2023). “The role of oxidative stress in kidney injury”. Antioxidants, 12(9), 1772. https://doi.org/10.3390/antiox12091772
  • 37. Akbas, A., Silan, C., Gulpinar, M.T., Sancak, E.B., Ozkanli, S.S., & Cakir, D.U. (2015). “Renoprotective effect of humic acid on renal ischemia-reperfusion injury: an experimental study in rats”. Inflammation, 38(5), 2042-2048. https://doi.org/10.1007/s10753-015-0182-2
  • 38. Hammoud, G.M., Nail, N.S., Abd El-Shafea, Y.M., & Salem, A.A. (2019). “Histopathological study on the protective effect of humic acid against aflatoxins induced-oxidative stress in rats”. International Journal of Advanced Research in Biological Sciences, 6(3), 111-127.
  • 39. Krstic, D., Tomic, N., Radosavljevic, B., Avramovic, N., Dragutinovic, V., Skodric, S.R., et al. (2016). “Biochemical markers of renal function”. Current Medicinal Chemistry, 23(19), 2018-2040. https://doi.org/10.2174/0929867323666160411120912
  • 40. Zanotti-Cavazzoni, S.L., & Goldfarb, R.D. (2009). “Animal models of sepsis”. Critical Care Clinics, 25(4), 703-719. https://doi.org/10.1016/j.ccc.2009.07.003
Toplam 40 adet kaynakça vardır.

Ayrıntılar

Birincil Dil Türkçe
Konular Acil Tıp
Bölüm Araştırma Makaleleri
Yazarlar

İhsan Karaboğa 0000-0001-6708-1229

Hamza Malik Okuyan 0000-0001-7616-3330

Serdar Doğan 0000-0001-6854-2197

Şeyda Öznur Ayçiçek 0000-0002-3922-8243

Mehmet Doğan 0000-0000-0000-0000

Hafize Kılınçkaya Doğan 0009-0005-6647-1803

Erken Görünüm Tarihi 25 Eylül 2025
Yayımlanma Tarihi 25 Eylül 2025
Gönderilme Tarihi 3 Temmuz 2025
Kabul Tarihi 11 Eylül 2025
Yayımlandığı Sayı Yıl 2025 Cilt: 14 Sayı: 3

Kaynak Göster

APA Karaboğa, İ., Okuyan, H. M., Doğan, S., … Ayçiçek, Ş. Ö. (2025). Humik Asit TNF-α İfadesini Düzenleyerek Lipopolisakkarit-uyarımlı Akut Böbrek Hasarını Hafifletir. Gümüşhane Üniversitesi Sağlık Bilimleri Dergisi, 14(3), 938-946. https://doi.org/10.37989/gumussagbil.1733539
AMA Karaboğa İ, Okuyan HM, Doğan S, Ayçiçek ŞÖ, Doğan M, Kılınçkaya Doğan H. Humik Asit TNF-α İfadesini Düzenleyerek Lipopolisakkarit-uyarımlı Akut Böbrek Hasarını Hafifletir. Gümüşhane Sağlık Bilimleri Dergisi. Eylül 2025;14(3):938-946. doi:10.37989/gumussagbil.1733539
Chicago Karaboğa, İhsan, Hamza Malik Okuyan, Serdar Doğan, Şeyda Öznur Ayçiçek, Mehmet Doğan, ve Hafize Kılınçkaya Doğan. “Humik Asit TNF-α İfadesini Düzenleyerek Lipopolisakkarit-uyarımlı Akut Böbrek Hasarını Hafifletir”. Gümüşhane Üniversitesi Sağlık Bilimleri Dergisi 14, sy. 3 (Eylül 2025): 938-46. https://doi.org/10.37989/gumussagbil.1733539.
EndNote Karaboğa İ, Okuyan HM, Doğan S, Ayçiçek ŞÖ, Doğan M, Kılınçkaya Doğan H (01 Eylül 2025) Humik Asit TNF-α İfadesini Düzenleyerek Lipopolisakkarit-uyarımlı Akut Böbrek Hasarını Hafifletir. Gümüşhane Üniversitesi Sağlık Bilimleri Dergisi 14 3 938–946.
IEEE İ. Karaboğa, H. M. Okuyan, S. Doğan, Ş. Ö. Ayçiçek, M. Doğan, ve H. Kılınçkaya Doğan, “Humik Asit TNF-α İfadesini Düzenleyerek Lipopolisakkarit-uyarımlı Akut Böbrek Hasarını Hafifletir”, Gümüşhane Sağlık Bilimleri Dergisi, c. 14, sy. 3, ss. 938–946, 2025, doi: 10.37989/gumussagbil.1733539.
ISNAD Karaboğa, İhsan vd. “Humik Asit TNF-α İfadesini Düzenleyerek Lipopolisakkarit-uyarımlı Akut Böbrek Hasarını Hafifletir”. Gümüşhane Üniversitesi Sağlık Bilimleri Dergisi 14/3 (Eylül2025), 938-946. https://doi.org/10.37989/gumussagbil.1733539.
JAMA Karaboğa İ, Okuyan HM, Doğan S, Ayçiçek ŞÖ, Doğan M, Kılınçkaya Doğan H. Humik Asit TNF-α İfadesini Düzenleyerek Lipopolisakkarit-uyarımlı Akut Böbrek Hasarını Hafifletir. Gümüşhane Sağlık Bilimleri Dergisi. 2025;14:938–946.
MLA Karaboğa, İhsan vd. “Humik Asit TNF-α İfadesini Düzenleyerek Lipopolisakkarit-uyarımlı Akut Böbrek Hasarını Hafifletir”. Gümüşhane Üniversitesi Sağlık Bilimleri Dergisi, c. 14, sy. 3, 2025, ss. 938-46, doi:10.37989/gumussagbil.1733539.
Vancouver Karaboğa İ, Okuyan HM, Doğan S, Ayçiçek ŞÖ, Doğan M, Kılınçkaya Doğan H. Humik Asit TNF-α İfadesini Düzenleyerek Lipopolisakkarit-uyarımlı Akut Böbrek Hasarını Hafifletir. Gümüşhane Sağlık Bilimleri Dergisi. 2025;14(3):938-46.