Evaluation of the Protective Effect of Quercetin against Cisplatin-Induced Acute Kidney Injury in Rats: A Biochemical and Histopathological Study

Jinan Tami  Shihan

doi:10.51699/cajotas.v7i4.1749

Authors

Jinan Tami Shihan Department of Theoretical Sciences, College of physical Education and Sports Science, Tikrit

DOI:

https://doi.org/10.51699/cajotas.v7i4.1749

Keywords:

Quercetin, Acute kidney injury, Cisplatin, Inflammation, Rats

Abstract

Acute kidney injury is among serious drug-induced adverse reactions. Cisplatin is one of the leading drugs causing nephrotoxicity mainly by generating free radicals and inflaming acute tissues. Excessive reactive oxygen species (ROS) production results in disruption of the redox balance, promotes lipid peroxidation, and consumes antioxidant systems like glutathione (GSH). Simultaneously, (SOD). activity decreases. Taken together, all these changes cause the failure of mitochondrial functions, loss of membrane integrity, and induction of proinflammatory pathways like that of B (NF-κB) and tumor necrosis factor-alpha (TNF-α). Besides that, these effects are reflected as histopathological changes, such as inflammatory cell infiltration congestion cellular degeneration and even necrosis in the worst cases. Antioxidants and anti-inflammatory properties are found in a few types of herbs like quercetin and they may have become important agents which reduce the risk of oxidative damage and inflammation, and they help to keep tissue together. This is achieved through boosting our natural ability to fight oxidative stress and altering the body's inflammatory mechanism, this way protecting the cells of the body. Yet, there is not enough clinical evidence to support the use of plants with such properties in all forms of kidney failure at this time, because of this, their usage remains confined to certain clinical support cases. Researches currently are concentrated on examining the protective effects of the natural antioxidant and anti-inflammatory flavonoid, the quercetin, in cisplatin-related severe kidney damage in the rat together with the changes that occur in the rat tissue structure due to this damage. Forty male Wistar rats weighing 200-250 g were randomly divided into four equal groups: a healthy control group, a cisplatin group, a quercetin group, and a cisplatin + quercetin group. Acute injury was induced via a single intraperitoneal injection of cisplatin (6 mg/kg), while quercetin (50 mg/kg) was administered daily for 14 days. After treatment, blood and tissue samples were taken for biochemical and histopathological studies. Measured serum levels of renal function markers included creatinine, urea and total protein, inflammatory mediators were )TNF-α,NF-κB,IL-1β), and antioxidant markers: )GSH,SOD(. All this was backed by histopathological analysis using Hematoxylin and Eosin (H&E) staining of the tissues. Cisplatin-treated animals showed a marked (p < 0.05) increase in the serum levels of creatinine, urea and inflammatory mediators while simultaneously a decrease in serum protein glutathione and superoxide dismutase was observed as evidenced by their blood tests. Their renal tissues, as examined microscopically, showed severe damage in tubular cells. Administration of queringetin with quite successfully reversed some of the pathological and biomorphological changes observed in cisplatin-treated group. The study concludes that quercetin offers a protective role against cisplatininduced nephrotoxicity and this may be due to the antioxidant and anti-inflammatory features of the compound.

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References

J. A. Kellum, P. Romagnani, G. Ashuntantang, C. Ronco, A. Zarbock, and H. J. Anders, “Acute kidney injury,” Nature Reviews Disease Primers, vol. 7, no. 1, p. 52, 2021.

D. Patschan and G. A. Müller, “Acute kidney injury,” Journal of Injury and Violence Research, vol. 7, no. 1, pp. 19–26, 2015.

J. M. Dennis and P. K. Witting, “Protective role for antioxidants in acute kidney disease,” Nutrients, vol. 9, no. 7, p. 718, 2017.

M. Chatatikun, A. Tedasen, R. Netphakdee, J. Tangpong, P. Phinyo, P. Wongyikul, et al., “The nephroprotective effects of alpha-mangostin for acute kidney injury: A systematic review and meta-analysis,” Antioxidants, vol. 14, no. 11, p. 1374, 2025.

N. Pabla and Z. Dong, “Cisplatin nephrotoxicity: Mechanisms and renoprotective strategies,” Kidney International, vol. 73, no. 9, pp. 994–1007, 2008.

R. P. Miller, R. K. Tadagavadi, G. Ramesh, and W. B. Reeves, “Mechanisms of cisplatin nephrotoxicity,” Toxins, vol. 2, no. 11, pp. 2490–2518, 2010.

C. Tang, M. J. Livingston, R. Safirstein, and Z. Dong, “Cisplatin nephrotoxicity: New insights and therapeutic implications,” Nature Reviews Nephrology, vol. 19, no. 1, pp. 53–72, 2023.

N. A. G. Santos, C. S. Catão, N. M. Martins, C. Curti, M. L. P. Bianchi, and A. C. Santos, “Cisplatin-induced nephrotoxicity is associated with oxidative stress, redox state unbalance, impairment of energetic metabolism and apoptosis in rat kidney mitochondria,” Archives of Toxicology, vol. 81, no. 7, pp. 495–504, 2007.

A. Ozkok and C. L. Edelstein, “Pathophysiology of cisplatin-induced acute kidney injury,” BioMed Research International, vol. 2014, p. 967826, 2014.

K. R. McSweeney, L. K. Gadanec, T. Qaradakhi, B. A. Ali, A. Zulli, and V. Apostolopoulos, “Mechanisms of cisplatin-induced acute kidney injury: Pathological mechanisms, pharmacological interventions, and genetic mitigations,” Cancers, vol. 13, no. 7, p. 1572, 2021.

Z. Wang, L. Zhao, L. Ren, and F. Yang, “Vindoline mitigates cisplatin-mediated kidney damage by alleviating redox imbalance, apoptosis and inflammation through extracellular signal-regulated kinase pathway modulation,” Journal of Physiology and Pharmacology, vol. 75, no. 3, p. 26402, 2024.

X. Yao, K. Panichpisal, N. Kurtzman, and K. Nugent, “Cisplatin nephrotoxicity: A review,” The American Journal of the Medical Sciences, vol. 334, no. 2, pp. 115–124, 2007.

L. M. G. Antunes, J. D. A. C. Darin, and M. L. P. Bianchi, “Protective effects of vitamin C against cisplatin-induced nephrotoxicity and lipid peroxidation in adult rats: A dose-dependent study,” Pharmacological Research, vol. 41, no. 4, pp. 405–411, 2000.

Y. T. Tarladacalisir, M. Kanter, and M. Uygun, “Protective effects of vitamin C on cisplatin-induced renal damage: A light and electron microscopic study,” Renal Failure, vol. 30, no. 1, pp. 1–8, 2008.

P. D. Sánchez-González, F. J. López-Hernández, M. Dueñas, M. Prieto, E. Sánchez-López, J. Thomale, et al., “Quercetin reduces cisplatin nephrotoxicity in rats without compromising its anti-tumour activity,” Nephrology Dialysis Transplantation, vol. 26, no. 11, pp. 3484–3492, 2011.

P. D. Sánchez-González, F. J. López-Hernández, M. Dueñas, M. Prieto, E. Sánchez-López, J. Thomale, et al., “Differential effect of quercetin on cisplatin-induced toxicity in kidney and tumor tissues,” Food and Chemical Toxicology, vol. 107, pp. 226–236, 2017.

A. G. Casanova, M. Prieto, C. I. Colino, C. Gutiérrez-Millán, B. Ruszkowska-Ciastek, E. de Paz, et al., “A micellar formulation of quercetin prevents cisplatin nephrotoxicity,” International Journal of Molecular Sciences, vol. 22, no. 2, p. 729, 2021.

D. Xu, M. J. Hu, Y. Q. Wang, and Y. L. Cui, “Antioxidant activities of quercetin and its complexes for medicinal application,” Molecules, vol. 24, no. 6, p. 1123, 2019.

R. Z. Tan, C. Wang, C. Deng, X. Zhong, Y. Yan, Y. Luo, et al., “Quercetin protects against cisplatin-induced acute kidney injury by inhibiting Mincle/Syk/NF-κB signaling maintained macrophage inflammation,” Phytotherapy Research, vol. 34, no. 1, pp. 139–152, 2020.

S. Alsawaf, F. Alnuaimi, S. Afzal, R. M. Thomas, A. L. Chelakkot, W. S. Ramadan, et al., “Plant flavonoids on oxidative stress-mediated kidney inflammation,” Biology, vol. 11, no. 12, p. 1717, 2022.

B. Fu, J. Yang, J. Chen, L. Lin, K. Chen, W. Zhang, et al., “Preventive effect of quercetin against inflammation-mediated diseases,” Frontiers in Immunology, vol. 13, p. 1023481, 2022.

J. Zhou, R. C. Nie, Y. X. Yin, X. X. Cai, D. Xie, and M. Y. Cai, “Protective effect of natural antioxidants on reducing cisplatin-induced nephrotoxicity,” Disease Markers, vol. 2022, p. 1612348, 2022.

F. Bagheri, A. Gol, and S. Dabiri, “Ameliorative effect of quercetin on renal function and tissue damage induced by cisplatin in male rats,” Physiology and Pharmacology, vol. 27, no. 1, pp. 60–70, 2023.

D. Muñoz-Reyes, A. G. Casanova, A. M. González-Paramás, Á. Martín, C. Santos-Buelga, A. I. Morales, et al., “Protective effect of quercetin 3-O-glucuronide against cisplatin cytotoxicity in renal tubular cells,” Molecules, vol. 27, no. 4, p. 1319, 2022.

M. Perše and Ž. Večerić-Haler, “Cisplatin-induced rodent model of kidney injury: Characteristics and challenges,” BioMed Research International, vol. 2018, p. 1462802, 2018.

E. B. Behling, M. C. Sendão, H. D. C. Francescato, L. M. G. Antunes, R. S. Costa, and M. L. P. Bianchi, “Comparative study of multiple dosage of quercetin against cisplatin-induced nephrotoxicity and oxidative stress in rat kidneys,” Pharmacological Reports, vol. 58, no. 4, pp. 526–532, 2006.

S. K. Suvarna, C. Layton, and J. D. Bancroft, Bancroft's Theory and Practice of Histological Techniques, 9th ed. Elsevier, 2024.

F. M. Kandemir, S. Küçükler, N. Akaras, C. Gür, and H. Şimşek, “Protective effects of quercetin against vincristine-induced nephrotoxicity via modulation of oxidative stress, inflammation, and apoptosis in rats,” Journal of Biochemical and Molecular Toxicology, vol. 39, no. 1, p. e70516, 2025.

I. Rahman, A. Kode, and S. K. Biswas, “Assay for quantitative determination of glutathione and glutathione disulfide levels using enzymatic recycling method,” Nature Protocols, vol. 1, no. 6, pp. 3159–3165, 2006.

S. Marklund and G. Marklund, “Involvement of the superoxide anion radical in the autoxidation of pyrogallol and a convenient assay for superoxide dismutase,” European Journal of Biochemistry, vol. 47, no. 3, pp. 469–474, 1974.

J. H. Zar, Biostatistical Analysis, 5th ed. Pearson Education, 2010.

S. Manohar and N. Leung, “Cisplatin nephrotoxicity: A review of the literature,” Journal of Nephrology, vol. 31, no. 1, pp. 15–25, 2018.

M. C. Oliveira, C. M. Bertollo, L. T. Rocha, and E. B. Nascimento, “Quercetin and its role in modulating the Nrf2/HO-1 and NF-κB pathways in renal inflammation,” Antioxidants, vol. 13, no. 6, p. 640, 2024.

M. Zhang, J. Zhang, Y. Ma, Y. Jin, Y. Li, and X. Wu, “Nephropathy induced by cisplatin results from mitochondrial disruption, impaired energy metabolism, altered expression of renal transporters, and accumulation of urinary toxins,” Journal of Trace Elements in Medicine and Biology, vol. 86, p. 127553, 2024, doi: 10.1016/j.jtemb.2024.127553.

H. Huang, W. W. Jin, M. Huang, H. Ji, D. E. Capen, Y. Xia, et al., “Gentamicin-induced acute kidney injury in an animal model involves programmed necrosis of the collecting duct,” Journal of the American Society of Nephrology, vol. 28, no. 1, pp. 130–142, 2017.

P. Tian, R. Hu, M. Xue, J. Liang, J. Li, and J. Li, “Inflammation: The pathological axis of cisplatin-induced renal injury,” Journal of Inflammation Research, vol. 19, pp. 1–20, 2026.

J. Zhuo, K. Wang, Z. Shi, and C. Yuan, “Reactive oxygen species and mitochondrial dysfunction in cisplatin-induced acute kidney injury,” Oxidative Medicine and Cellular Longevity, vol. 2022, p. 6612548, 2022.

D. R. M. Krishna, K. Sandeep, and G. D. Reddy, “Reactive oxygen species: Physiological roles and pathological implications,” Journal of Applied Biology & Biotechnology, vol. 11, no. 2, pp. 1–9, 2023.

Y. Özkul, S. Silici, and E. Eroğlu, “Cisplatin-induced oxidative stress and histopathological damage in rat kidney: Protective approaches,” Toxicology Reports, vol. 10, pp. 512–520, 2023.

P. Ravindra, D. A. Bhiwgade, S. Kulkarni, P. V. Rataboli, and C. Y. Dhume, “Cisplatin induced histological changes in renal tissue of rat,” Journal of Cell and Animal Biology, vol. 4, no. 7, pp. 108–111, 2010.

W. F. Fathy and S. A. Hassan, “Histopathological study of the effect of cisplatin on the kidney of Swiss albino BALB/c mice,” Journal of Education and Science, vol. 28, no. 1, 2019.

U. W. Edwin, “Gross morphological changes in cisplatin-induced nephrotoxicity among the Wistar albino rats,” Mediterranean Journal of Basic and Applied Sciences, vol. 9, no. 2, pp. 17–22, 2025.