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Journals / Uludağ Üniversitesi Tıp Fakültesi Dergisi / 2026 / Cilt: 52

The Effect of Copper Sulfate on Aquaporins in Kidney Tissue

Böbrek Dokusunda Akuaporinler Üzerine Bakır Sülfat Etkisi

Selda Kahveci(Department of Histology and Embryology, Faculty of Medicine, Yozgat Bozok University, Yozgat, Türkiye.)0000-0002-0734-6720
Tahsin Selvi(Department of Histology and Embryology, School of Graduate Studies, Yozgat Bozok University, Yozgat, Türkiye.)0009-0004-4944-5091
Şaban Varinli(Department of Histology and Embryology, School of Graduate Studies, Yozgat Bozok University, Yozgat, Türkiye.)0000-0003-0621-5726
Taha Berkay Bor(Department of Histology and Embryology, Faculty of Medicine, Yozgat Bozok University, Yozgat, Türkiye.)0009-0002-2437-9257
Züleyha Doğanyiğit(Department of Histology and Embryology, Faculty of Medicine, Yozgat Bozok University, Yozgat, Türkiye.)0000-0002-6980-3384
Osman Öztürks(Department of Child Health and Diseases, Faculty of Medicine, Yozgat Bozok University, Yozgat, Türkiye.)0000-0003-1156-7419
Aslı Okan Oflamaz(Department of Histology and Embryology, Faculty of Medicine, Yozgat Bozok University, Yozgat, Türkiye.)0000-0001-8152-7338
Sümeyye Uçar(Department of Anatomy, Faculty of Medicine, Erciyes University, Erciyes, Türkiye.)0000-0003-3378-3745
Seher Yılmaz(Department of Anatomy, Faculty of Medicine, Yozgat Bozok University, Yozgat, Türkiye.)0000-0003-4551-995X
Pages
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Publication Date
2026-03-17
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AI Summary & Key Takeaways

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

These findings suggest that CuSO4 may have re-modulated AQP-1 and AQP-3 levels due to the tubular vacuolization and degeneration it caused; however, the effect of CuSO4 on estrogen levels in females and the vasopressin effect via AQP-2 need to be investigated in detail.

📌 3 Key Takeaways

🎯
Objective & Hypothesis:Copper (Cu) is a cofactor for most enzymes and an essential trace element.
📊
Key Findings & Data:In our study, we aimed to evaluate the expression of AQP-1, -2, and -3 in the kidneys of female and male rats following the administration of high-dose copper sulfate (CuSO4).
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Conclusion & Impact:These findings suggest that CuSO4 may have re-modulated AQP-1 and AQP-3 levels due to the tubular vacuolization and degeneration it caused; however, the effect of CuSO4 on estrogen levels in females and the vasopressin effect via AQP-2 need to be investigated in detail.
🔬Design:Araştırma Makalesi
📍Scope:Comprehensive Sample
⚙️Variables:Akuaporinler · Bakır Sülfat · Böbrek

Abstract

Copper (Cu) is a cofactor for most enzymes and an essential trace element. However, elevated levels of Cu exposure cause toxic effects in various tissues. Aquaporins (AQP) are integral membrane proteins that play a key role in fluid transport, particularly in kidney tissues. In our study, we aimed to evaluate the expression of AQP-1, -2, and -3 in the kidneys of female and male rats following the administration of high-dose copper sulfate (CuSO4). First, the control group (n=10) received saline via oral gavage, while the experimental group (CuSO4) (n=10) received 100 mg/kg/day via oral gavage for 14 days. Histopathological, PAS staining, and immunohistochemical evaluation of AQP-1, -2, and -3 were then performed on kidney tissues from the control and experimental groups. CuSO4 caused tubular vacuolization in the kidneys. CuSO4 administration decreased AQP-2 levels while increasing AQP-1 and AQP-3 levels. These findings suggest that CuSO4 may have re-modulated AQP-1 and AQP-3 levels due to the tubular vacuolization and degeneration it caused; however, the effect of CuSO4 on estrogen levels in females and the vasopressin effect via AQP-2 need to be investigated in detail.

Özet

Bakır (Cu), çoğu enzimin kofaktörü ve temel bir eser elementtir. Ancak, yüksek düzeyde Cu maruziyeti çeşitli dokularda toksik etkilere neden olur. Akuaporinler (AQP), sıvı taşınmasında, özellikle böbrek dokularında önemli bir rol oynayan integral membran proteinleridir. Çalışmamızda, yüksek doz bakır sülfat (CuSO4) uygulamasının ardından dişi ve erkek sıçanların böbreklerinde AQP-1, -2 ve -3 ekspresyonunu değerlendirmeyi amaçladık. İlk olarak, kontrol grubuna (n=10) oral gavaj yoluyla salin verilirken, deney grubuna (CuSO4) (n=10) 14 gün boyunca oral gavaj yoluyla 100 mg/kg/gün CuSO4 verildi. Daha sonra kontrol ve deney gruplarının böbrek dokularında AQP-1, -2 ve -3'ün histopatolojik, PAS boyama ve immünohistokimyasal değerlendirmeleri yapıldı. CuSO4, böbreklerde tübüler vakuolizasyona neden oldu. CuSO4 uygulaması, AQP-1 ve AQP-3 düzeylerini artırırken AQP-2 düzeylerini düşürdü. Bu bulgular, CuSO4'ün neden olduğu tübüler vakuolizasyon ve dejenerasyon nedeniyle AQP-1 ve AQP-3 düzeylerini yeniden modüle etmiş olabileceğini düşündürmektedir; ancak CuSO4'ün dişilerdeki östrojen düzeyleri üzerindeki etkisi ve AQP-2 aracılığıyla vazopressin etkisi ayrıntılı olarak araştırılmalıdır.

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Cite This Article

Kahveci, S., Selvi, T., Varinli, Ş., Bor, T. B., Doğanyiğit, Z., Öztürks, O., Oflamaz, A. O., Uçar, S., Yılmaz, S., *, S. K. (2026). The Effect of Copper Sulfate on Aquaporins in Kidney Tissue. Uludağ Üniversitesi Tıp Fakültesi Dergisi, Cilt: 52. https://doi.org/10.32708/uutfd.1886172

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References (45)

  1. Fraga CG. Relevance, essentiality and toxicity of trace elements in human health. Mol Aspects Med. 2005;26(4-5):235-244.
  2. Kumar V, Kalita J, Bora HK, Misra UK. Relationship of antioxidant and oxidative stress markers in different organs following copper toxicity in a rat model. Toxicol Appl Pharmacol. 2016;293:37-43.
  3. Valko M, Jomova K, Rhodes CJ, Kuca K, Musilek K. Redox- and non-redox-metal-induced formation of free radicals and their role in human disease. Arch Toxicol. 2016;90(1):1-37.
  4. Shim H, Harris ZL. Genetic defects in copper metabolism. J Nutr. 2003;133(5 Suppl 1):1527S-1531S.
  5. Scheiber IF, Mercer JF, Dringen R. Metabolism and functions of copper in brain. Prog Neurobiol. 2014;116:33-57.
  6. Arnal N, Dominici L, de Tacconi MJ, Marra CA. Copper-induced alterations in rat brain depends on route of overload and basal copper levels. Nutrition. 2014;30(1):96-106.
  7. Kozlowski H, Janicka-Klos A, Brasun J, et al. Copper, iron, and zinc ions homeostasis and their role in neurodegenerative disorders (metal uptake, transport, distribution and regulation). Coordination Chemistry Reviews. 2009;253(21-22):2665-2685.
  8. Toyokini S OS, Hamazaki S, Fujoka M, Li JL, Midorikawa O. Cirrhosis of the liver induced by cupric nitrilotriacetate in Wistar rats. An experimental model of copper toxicosis. Am J Pathol. 1989;134:1263-1274.
  9. Zhao H, Wang Y, Fei D, et al. Destruction of redox and mitochondrial dynamics co-contributes to programmed cell death in chicken kidney under arsenite or/and copper (II) exposure. Ecotoxicol Environ Saf. 2019;179:167-174.
  10. Waggoner DJ BT, Gitlin JD. The role of copper in neurodegenerative disease. Neurobiol Dis. 1999;6:221-230.
  11. Kahveci S, Ozturk O, Ucar S, et al. Effect of copper sulphate in rat brain tissue: Kir channels. Turkish Bulletin of Hygiene and Experimental Biology. 2024;81(4):419-430.
  12. Scheinberg IH, Sternlieb I. Wilson disease and idiopathic copper toxicosis. Am J Clin Nutr. 1996;63(5):842S-845S.
  13. Fuentealba ICH, S.; Foster, J. Cellular mechanisms of toxicity and tolerance in the copper-loaded rat. III. Ultrastructural changes and copper localization in the kidney. Br J Exp Pathol 1989;70:543-556.
  14. Dai C, Liu Q, Li D, et al. Molecular Insights of Copper Sulfate Exposure-Induced Nephrotoxicity: Involvement of Oxidative and Endoplasmic Reticulum Stress Pathways. Biomolecules. 2020;10(7):1010.
  15. Peng X, Dai C, Zhang M, Das Gupta S. Molecular Mechanisms Underlying Protective Role of Quercetin on Copper Sulfate-Induced Nephrotoxicity in Mice. Front Vet Sci. 2020;7:586033.
  16. Ghara AR. GF. Effect of purslane on kidney failure following copper toxicity in a rat model. Iranian Journal of Health Sciences 2018;6(1):25-32.
  17. Lv W, Liao J, Li C, et al. Aquaporin 1 is renoprotective in septic acute kidney injury by attenuating inflammation, apoptosis and fibrosis through inhibition of P53 expression. Front Immunol. 2024;15:1443108.
  18. Hua Y, Ying X, Qian Y, et al. Physiological and pathological impact of AQP1 knockout in mice. Biosci Rep. 2019;39(5).
  19. Su W, Cao R, Zhang XY, Guan Y. Aquaporins in the kidney: physiology and pathophysiology. Am J Physiol Renal Physiol. 2020;318(1):F193-F203.
  20. Pallone TL KB, Nielsen S, Agre P, Knepper MA. Evidence that aquaporin-1 mediates NaCl-induced water flux across descending vasa recta Am J Physiol Renal Physiol 1997;272:F587-F596.
  21. Tajika Y MT, Suzuki T, Aoki T, Hagiwara H, Tanaka S, Kominami E, Takata K. Immunohistochemicalcharacterization of the intracellular pool of water channelaquaporin-2 in the rat kidney. Anato Sci Int. 2002;77:189-195.
  22. Ma T SY, Yang B, Gillespie A, Carlson EJ, Epstein CJ,Verkman AS. Nephrogenic diabetes insipidus in mice lackingaquaporin-3 water channels. PNAS. 2000;97:4386-4391.
  23. Lei L, Wang W, Jia Y, et al. Aquaporin-3 deletion in miceresults in renal collecting duct abnormalities and worsensischemia-reperfusion injury. Biochim Biophys Acta Mol Basis Dis. 2017;1863(6):1231-1241.
  24. Liu JY, Yang X, Sun XD, et al. Suppressive Effects of CopperSulfate Accumulation on the Spermatogenesis of Rats. Biol Trace Elem Res. 2016;174(2):356-361.
  25. Nangaku M, Alpers CE, Pippin J, et al. A new model of renalmicrovascular endothelial injury. Kidney Int. 1997;52(1):182-194.
  26. Doganyigit Z, Okan A, Taheri S, et al. Evaluation of linagliptinand insulin combined therapy on unfolded protein response intype 1 diabetic mouse heart. Chem Biol Drug Des. 2023;102(5):1085-1096.
  27. Yulug E, Turedi S, Yildirim O, et al. Biochemical andmorphological evaluation of the effects of propolis on cisplatininduced kidney damage in rats. Biotech Histochem. 2019;94(3):204-213.
  28. Ghosh SS MH, Krieg R, Fazelbhoy ZA, Ghosh S, Sica DA,Fakhry I, Gehr TW. Curcumin ameliorates renal failure in 5/6nephrectomized rats: role of inflammation. Am J Physiol RenalPhysiol 2009;296(5):F1146-1157.
  29. Kumar V, Kalita J, Bora HK, Misra UK. Temporal kinetics oforgan damage in copper toxicity: A histopathologicalcorrelation in rat model. Regul Toxicol Pharmacol.2016;81:372-380.
  30. Uçar S, Yılmaz S, Ateş Ş, et al. Prenatal Exposure to CopperSulfate: Effects on Fetal Development in Rats. BratislavaMedical Journal. 2026.
  31. Erfanizadeh M, Noorafshan A, Naseh M, Karbalay-Doust S.The effects of copper sulfate on the structure and function ofthe rat cerebellum: A stereological and behavioral study. IBRONeurosci Rep. 2021;11:119-127.
  32. Kalita J, Kumar V, Misra UK, Bora HK. Movement Disorder inCopper Toxicity Rat Model: Role of Inflammation andApoptosis in the Corpus Striatum. Neurotox Res. 2020;37(4):904-912.
  33. Wang Y ZH, Shao Y, Liu J, Li J, Xing M. Copper or/and arsenic induce oxidative stress-cascaded, nuclear factor kappa B-dependent inflammation and immune imbalance, trigging heat shock response in the kidney of chicken. Oncotarget. 2017;8:98103-98116.
  34. Kumar V, Kalita J, Misra UK, Bora HK. A study of doseresponse and organ susceptibility of copper toxicity in a ratmodel. J Trace Elem Med Biol. 2015;29:269-274.
  35. Feraille E, Sassi A, Olivier V, Arnoux G, Martin PY. Renalwater transport in health and disease. Pflugers Arch.2022;474(8):841-852.
  36. Vallon V, Verkman, A.S. and Schnermann, J. Luminalhypotonicity in proximal tubules of aquaporin-1-knockout mice. Am J Physiol Renal Physiol. 2000(278):1030-1033.
  37. Abdelrahaman D, Shanab O, Abdeen A, et al. Bee venomameliorates gentamicin-induced kidney injury by restoring renal aquaporins and enhancing antioxidant and anti-inflammatory activities in rats. Front Pharmacol. 2025;16:1525529.
  38. Marrone J, Lehmann GL, Soria LR, et al. Adenoviral transfer ofhuman aquaporin-1 gene to rat liver improves bile flow inestrogen-induced cholestasis. Gene Ther. 2014;21(12):1058-1064.
  39. Nguyen H, Huynh NV, Hyndman KA. Diurnal function andexpression of aquaporins in the mouse kidney. Am J PhysiolRenal Physiol. 2025;329(5):F601-F614.
  40. Michalek K, Oberska P, Murawski M, et al. Kidneymorphology and renal expression of aquaporins 2, 3 and 4during cerulein - Induced chronic pancreatitis in pigs. Adv MedSci. 2023;68(2):306-313.
  41. Mariajoseph-Antony LF, Kannan A, Panneerselvam A, et al.Role of Aquaporins in Inflammation-a Scientific Curation.Inflammation. 2020;43(5):1599-1610.
  42. Hasler U, Leroy V, Jeon US, et al. NF-kappaB modulatesaquaporin-2 transcription in renal collecting duct principalcells. J Biol Chem. 2008;283(42):28095-28105.
  43. Marples D FJ, Dørup J, Knepper MA, Nielsen S. Hypokalemia-induced downregulation of aquaporin-2 water channelexpression in rat kidney medulla and cortex. J Clin Invest.1996;97(08):1960-1968.
  44. Hussein AA, El-Dken ZH, Barakat N, Abol-Enein H. Renalischaemia/reperfusion injury: possible role of aquaporins. Acta Physiol (Oxf). 2012;204(3):308-316.
  45. Oliveira dV, Schaefer J, Abu-Rafea B, et al. Uterine aquaporinexpression is dynamically regulated by estradiol andprogesterone and ovarian stimulation disrupts embryoimplantation without affecting luminal closure. Mol HumReprod. 2020;26(3):154-166.