Reports of Biochemistry
and Molecular Biology
Wed, Jul 30, 2025
[Archive]
Volume 13, Issue 4 (Vol.13 No.4 Jan 2025)
rbmb.net 2025, 13(4): 579-589 |
Back to browse issues page
Download citation:
BibTeX | RIS | EndNote | Medlars | ProCite | Reference Manager | RefWorks
Send citation to:
BibTeX | RIS | EndNote | Medlars | ProCite | Reference Manager | RefWorks
Send citation to:
Karimi S, Koohpeyma F, Khorsandi L, Panahi A, Rezaei-Tazangi F, Fakhredini F. Comparative Analysis of Curcumin and Metformin Effects on the Kidney in a Model of Unilateral Nephrectomy and Ischemia-Reperfusion Injury. rbmb.net 2025; 13 (4) :579-589
URL: http://rbmb.net/article-1-1570-en.html
URL: http://rbmb.net/article-1-1570-en.html
Samaneh Karimi 
, Farhad Koohpeyma , Layasadat Khorsandi , Armin Panahi , Fatemeh Rezaei-Tazangi , Fereshtesadat Fakhredini *
, Farhad Koohpeyma , Layasadat Khorsandi , Armin Panahi , Fatemeh Rezaei-Tazangi , Fereshtesadat Fakhredini *
Cellular and Molecular Research Center, Medical Basic Sciences Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran & Department of Anatomical Sciences, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
Abstract: (227 Views)
Background: Unilateral nephrectomy and renal ischemia-reperfusion injury (I/R) are causes of acute kidney injury that can cause renal dysfunction, decreased glomerular filtration rate, impaired homeostasis, and increased mortality. This study aimed to evaluate the combined effects of curcumin (Cur) and metformin (Met), both protective antioxidants, on renal tissue structure and Neutrophil gelatinase-associated lipocalin (Ngal) and Kidney injury molecule 1 (Kim-1) genes expression levels in rats undergoing unilateral nephrectomy and ischemia/reperfusion.
Methods: In this experimental study, 40 male rats were randomly divided into five groups. The animals underwent unilateral nephrectomy and ischemia/reperfusion and were then treated with curcumin and metformin or both for 14 days. Subsequently, histopathological and morphometric analyses were performed, and Ngal and Kim-1 gene expression levels were evaluated using real-time PCR.
Results: Histopathological damage, expression levels of blood urea nitrogen (BUN), creatinine (Cr), blood biochemical parameters and oxidative stress and expression levels of Ngal and Kim-1 genes were significantly reduced in the patient group that received metformin and curcumin simultaneously. However, total antioxidant capacity (TAC) was increased in the patient group that received curcumin + metformin. Morphometric parameters also improved in this group.
Conclusion: The results showed that the combination therapy with curcumin and metformin effectively protected the kidneys against unilateral nephrectomy and I/R injury.
Methods: In this experimental study, 40 male rats were randomly divided into five groups. The animals underwent unilateral nephrectomy and ischemia/reperfusion and were then treated with curcumin and metformin or both for 14 days. Subsequently, histopathological and morphometric analyses were performed, and Ngal and Kim-1 gene expression levels were evaluated using real-time PCR.
Results: Histopathological damage, expression levels of blood urea nitrogen (BUN), creatinine (Cr), blood biochemical parameters and oxidative stress and expression levels of Ngal and Kim-1 genes were significantly reduced in the patient group that received metformin and curcumin simultaneously. However, total antioxidant capacity (TAC) was increased in the patient group that received curcumin + metformin. Morphometric parameters also improved in this group.
Conclusion: The results showed that the combination therapy with curcumin and metformin effectively protected the kidneys against unilateral nephrectomy and I/R injury.
Type of Article: Original Article |
Subject:
Biochemistry
Received: 2025/01/25 | Accepted: 2025/03/7 | Published: 2025/07/30
Received: 2025/01/25 | Accepted: 2025/03/7 | Published: 2025/07/30
References
1. Gupta G, Gupta N, Pandey D, Gupta G.Acute renal failure: A case series (Part 3). Adv Homeopathy Res. 2024;8(4):33-8. [DOI:10.48165/ahr.2023.8.4.3]
2. Yıldız F, Güngör M, Sezginer P, Aksak T. A histological examination of the effects of Ferula elaeochytris extract on kidney and liver tissues in myoglobinuric acute renal failure. Biotech Histochem. 2024;99(3):103-112. [DOI:10.1080/10520295.2024.2323973] [PMID]
3. Taniguchi A, Miyashita K, Fukae S, Tanaka R, Nishida M, Kitayama T, et al. Single-cell transcriptome analysis of a rat model of bilateral renal ischemia-reperfusion injury. Biochem Biophys Rep. 2023;33:101433. [DOI:10.1016/j.bbrep.2023.101433] [PMID] []
4. Ruas AF, Lébeis GM, de Castro NB, Palmeira VA, Costa LB, Lanza K, et al. Acute kidney injury in pediatrics: an overview focusing on pathophysiology. Pediatr Nephrol. 2022;37(9):2037-2052. [DOI:10.1007/s00467-021-05346-8] [PMID]
5. Van Smaalen TC, Beurskens DM, Kox JJ, Polonia R, Vos R, Duimel H, et al. Extracellular histone release by renal cells after warm and cold ischemic kidney injury: Studies in an ex-vivo porcine kidney perfusion model. PLoS One. 2023;18(1):e0279944. [DOI:10.1371/journal.pone.0279944] [PMID] []
6. Wasung ME, Chawla LS, Madero M. Biomarkers of renal function, which and when? Clin Chim Acta. 2015; 438:350-7. [DOI:10.1016/j.cca.2014.08.039] [PMID]
7. Hu L, Zhao Z. Evaluation of urinary neutrophil gelatinase associated lipocalin in the early diagnosis of acute kidney injury with sepsis. Am J Transl Res. 2024;16(4):1266. [DOI:10.62347/PMAL7041] [PMID] []
8. Ghadrdan E, Ebrahimpour S, Sadighi S, Chaibakhsh S, Jahangard-Rafsanjani Z. Evaluation of urinary neutrophil gelatinase-associated lipocalin and urinary kidney injury molecule-1 as biomarkers of renal function in cancer patients treated with cisplatin. J Oncol Pharm Pract. 2020;26(7):1643-9. [DOI:10.1177/1078155220901756] [PMID]
9. Bahmani M, Rafieian-Kopaei M, Naghdi N, Nejad AS, Afsordeh O. Physalis alkekengi: A review of its therapeutic effects. J Chem Pharm Sci. 2016;9(3):1472-75.
10. Badiee MS, Vadizadeh A, Salehcheh M, Moosavi M, Shirani M, Fakhredini F, Khodayar MJ. Quercetin and Catechin Protects Leptin-Deficient Lepob/Ob Mice Against Alloxan-Induced Diabetes and Hepatotoxicity via Suppression of Oxidative Stress and Inflammation. Rep Biochem Mol Biol. 2024; 13(2):184-195. [DOI:10.61186/rbmb.13.2.184] [PMID] []
11. AloK A, Singh ID, Singh S, Kishore M, Jha PC. Curcumin-pharmacological actions and its role in oral submucous fibrosis: a review. J Clinical Diagnostic res. 2015;9(10): ZE01-3. [DOI:10.7860/JCDR/2015/13857.6552] [PMID] []
12. He L, Peng X, Zhu J, Liu G, Chen X, Tang C, et al. Protective effects of curcumin on acute gentamicin-induced nephrotoxicity in rats. Can J Physiol Pharmacol. 2015;93(4):275-82. [DOI:10.1139/cjpp-2014-0459] [PMID]
13. Vial G, Detaille D, Guigas B. Role of mitochondria in the mechanism (s) of action of metformin. Front Endocrinol (Lausanne). 2019; 10:294. [DOI:10.3389/fendo.2019.00294] [PMID] []
14. Wang G, Wang Y, Yang Q, Xu C, Zheng Y, Wang L, et al. Metformin prevents methylglyoxal-induced apoptosis by suppressing oxidative stress in vitro and in vivo. Cell Death Dis. 2022;13(1):29.
https://doi.org/10.1038/s41419-019-2218-5 [DOI:10.1038/s41419-021-04478-x]
15. Song A, Zhang C, Meng X. Mechanism and application of metformin in kidney diseases: An update. Biomed Pharmacother. 2021; 138:111454. [DOI:10.1016/j.biopha.2021.111454] [PMID]
16. Dugbartey GJ, Bouma HR, Saha MN, Lobb I, Henning RH, Sener A. Hydrogen Sulfide Therapy as the Future of Renal Graft Preservation. In: Hydrogen Sulfide in Kidney Diseases. Springer, Cham. 2023. [DOI:10.1007/978-3-031-44041-0]
17. Antar SA, Abd-Elsalam M, Abdo W, Abdeen A, Abdo M, Fericean L, et al. Modulatory role of autophagy in metformin therapeutic activity toward doxorubicin-induced nephrotoxicity. Toxics. 2023;11(3):273. [DOI:10.3390/toxics11030273] [PMID] []
18. Reis DC, Alvarenga L, Cardozo LF, Baptista BG, Fanton S, Paiva BR, et al. Can curcumin supplementation break the vicious cycle of inflammation, oxidative stress, and uremia in patients undergoing peritoneal dialysis? Clin Nutr ESPEN. 2024; 59:96-106. [DOI:10.1016/j.clnesp.2023.11.015] [PMID]
19. Li H, Sun H, Xu Y, Xing G, Wang X. Curcumin plays a protective role against septic acute kidney injury by regulating the TLR9 signaling pathway. Transl Androl Urol. 2021;10(5):2103-2112. [DOI:10.21037/tau-21-385] [PMID] []
20. Damiano S, Andretta E, Longobardi C, Prisco F, Paciello O, Squillacioti C, et al. Effects of curcumin on the renal toxicity induced by ochratoxin A in rats. Antioxidants (Basel). 2020;9(4):332. [DOI:10.3390/antiox9040332] [PMID] []
21. Zhao YH, Shen CF, Wang GJ, Kang Y, Song YH, Liu JW. Curcumin alleviates acute kidney injury in a dry‐heat environment by reducing oxidative stress and inflammation in a rat model. J Biochem Mol Toxicol. 2021;35(1):e22630. [DOI:10.1002/jbt.22630] [PMID] []
22. Ige AO, Chidi RN, Egbeluya EE, Jubreel RO, Adele BO, Adewoye EO. Amelioration of thyroid dysfunction by magnesium in experimental diabetes may also prevent diabetes-induced renal impairment. Heliyon. 2019; 5(5):e01660. [DOI:10.1016/j.heliyon.2019.e01660] [PMID] []
23. Wang Y, Wang Y, Li Y, Lu L, Peng Y, Zhang S, Xia A. Metformin attenuates renal interstitial fibrosis through upregulation of Deptor in unilateral ureteral obstruction in rats. Exp Ther Med. 2020;20(5):17. [DOI:10.3892/etm.2020.9144] [PMID] []
24. Fakhredini F, Mansouri E, Mard SA, Valizadeh Gorji A, Rashno M, Orazizadeh M. Effects of Exosomes Derived from Kidney Tubular Cells on Diabetic Nephropathy in Rats. Cell J. 2022;24(1):28-35.
25. Dare A, Channa ML, Nadar A. L-ergothioneine and its combination with metformin attenuates renal dysfunction in type-2 diabetic rat model by activating Nrf2 antioxidant pathway. Biomed Pharmacother. 2021;141:111921. [DOI:10.1016/j.biopha.2021.111921] [PMID]
26. Zhai J, Chen Z, Zhu Q, Guo Z, Wang N, Zhang C, et al. The Protective Effects of Curcumin against Renal Toxicity. Curr Med Chem. 2024;31(35):5661-5669. [DOI:10.2174/0109298673271161231121061148] [PMID]
27. Abd El-Kader M, Taha RI. Comparative nephroprotective effects of curcumin and etoricoxib against cisplatin-induced acute kidney injury in rats. Acta Histochemica. 2020;122(4):151534. [DOI:10.1016/j.acthis.2020.151534] [PMID]
28. Soetikno V, Sari SDP, Ul Maknun L, Sumbung NK, Rahmi DNI, Pandhita BAW, et al. Pre-Treatment with Curcumin Ameliorates Cisplatin-Induced Kidney Damage by Suppressing Kidney Inflammation and Apoptosis in Rats. Drug Res (Stuttg). 2019;69(2):75-82. [DOI:10.1055/a-0641-5148] [PMID]
29. Zeni L, Norden AGW, Cancarini G, Unwin RJ. A more tubulocentric view of diabetic kidney disease. J Nephrol. 2017;30(6):701-717. [DOI:10.1007/s40620-017-0423-9] [PMID] []
30. Qi R, Yang C. Renal tubular epithelial cells: the neglected mediator of tubulointerstitial fibrosis after injury. Cell death & disease. 2018;9(11):1126. [DOI:10.1038/s41419-018-1157-x] [PMID] []
31. Guzzi F, Cirillo L, Roperto RM, Romagnani P, Lazzeri E. Molecular mechanisms of the acute kidney injury to chronic kidney disease transition: an updated view. Int J Mol Sci. 2019;20(19):4941. [DOI:10.3390/ijms20194941] [PMID] []
32. Pan P, Huang YW, Oshima K, Yearsley M, Zhang J, Arnold M, et al. The immunomodulatory potential of natural compounds in tumor-bearing mice and humans. Crit Rev Food Sci Nutr. 2019;59(6):992-1007. [DOI:10.1080/10408398.2018.1537237] [PMID] []
33. Abdel-Tawab MS, Mostafa Tork O, Mostafa-Hedeab G, Ewaiss Hassan M, Azmy Elberry D. Protective Effects of Quercetin and Melatonin on Indomethacin Induced Gastric Ulcers in Rats. Rep Biochem Mol Biol. 2020;9(3):278-290. [DOI:10.29252/rbmb.9.3.278] [PMID] []
34. Tanase DM, Gosav EM, Radu S, Costea CF, Ciocoiu M, Carauleanu A, et al. The Predictive Role of the Biomarker Kidney Molecule-1 (KIM-1) in Acute Kidney Injury (AKI) Cisplatin-Induced Nephrotoxicity. Int J Mol Sci. 2019;20(20):5238. [DOI:10.3390/ijms20205238] [PMID] []
35. Al Fayi M, Otifi H, Alshyarba M, Dera AA, Rajagopalan P. Thymoquinone and curcumin combination protects cisplatin-induced kidney injury, nephrotoxicity by attenuating NFκB, KIM-1 and ameliorating Nrf2/HO-1 signalling. J Drug Target. 2020;28(9):913-22. [DOI:10.1080/1061186X.2020.1722136] [PMID]
36. Liu FH, Ni WJ, Wang GK, Zhang JJ. Protective role of curcumin on renal ischemia reperfusion injury via attenuating the inflammatory mediators and Caspase-3. Cell Mol Biol (Noisy-le-grand). 2016;62(11):95-99.
37. Zhang B, Chen ZY, Jiang Z, Huang S, Liu XH, Wang L. Nephroprotective Effects of Cardamonin on Renal Ischemia Reperfusion Injury/UUO-Induced Renal Fibrosis. J Agric Food Chem. 2023;71(36):13284-303. [DOI:10.1021/acs.jafc.3c01880] [PMID] []
38. Zarbock A, Forni LG, Ostermann M, Ronco C, Bagshaw SM, Mehta RL, et al. Designing acute kidney injury clinical trials. Nat Rev Nephrol. 2024;20(2):137-46. [DOI:10.1038/s41581-023-00758-1] [PMID]
Send email to the article author
| Rights and permissions | |
 |
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |
