Author(s):
Mamta Rajpurohit, Jagdish Kakadiya
Email(s):
rajpurohitmamta0829@gmail.com
DOI:
10.52711/0974-360X.2026.00065 
Address:
Mamta Rajpurohit1, Jagdish Kakadiya2
1M. Pharm Scholar, Department of Pharmacology, Parul Institute of Pharmacy and Research, Parul University, Limda, Vadodara, Gujarat, India.
2Professor, Department of Pharmacology, Parul Institute of Pharmacy and Research, Parul University, Limda, Vadodara, Gujarat, India.
*Corresponding Author
Published In:
Volume - 19,
Issue - 1,
Year - 2026
ABSTRACT:
Nephrotoxicity refers to the harmful effects that different substances can exert on kidney function. Various agents, such as non-steroidal agents (Acetaminophen and Diclofenac Sodium), antifungal (Amphotericin B), antiviral (Acyclovir), aminoglycosides (Gentamicin), immunosuppressant drugs (Cyclosporine, Tacrolimus), and anticancer agents (Cisplatin), can cause nephrotoxic effects. This review examines the mechanisms behind drug-induced nephrotoxicity, which include alternations in glomerular hemodynamics, tubular cells toxicity, inflammation, crystal nephropathy, rhabdomyolysis, and thrombotic microangiopathy. Animal models are crucial for understanding nephrotoxicity mechanisms and developing effective therapies for its management. Due to the numerous pathways that can lead to renal impairment, a wide range of animal models has been established to mirror the clinical manifestations of renal impairment. This review aims to assist in selecting an appropriate model for evaluating new drugs that could protect against nephrotoxicity.
Cite this article:
Mamta Rajpurohit, Jagdish Kakadiya. Mechanisms of Drug-induced Nephrotoxicity: A Comprehensive Analysis using Animal Models. Research Journal of Pharmacy and Technology. 2026;19(1):446-1. doi: 10.52711/0974-360X.2026.00065
Cite(Electronic):
Mamta Rajpurohit, Jagdish Kakadiya. Mechanisms of Drug-induced Nephrotoxicity: A Comprehensive Analysis using Animal Models. Research Journal of Pharmacy and Technology. 2026;19(1):446-1. doi: 10.52711/0974-360X.2026.00065 Available on: https://rjptonline.org/AbstractView.aspx?PID=2026-19-1-65
REFERENCES:
1. Ferguson MA, Vaidya VS, Bonventre JV. Biomarkers of nephrotoxic acute kidney injury. Toxicology. 2008; 245(3): 182-93. doi:10.1016/j.tox.2007.12.024
2. Siew ED, Davenport A. The growth of acute kidney injury: a rising tide or just closer attention to detail?. Kidney International. 2015; 87(1): 46-61. doi:10.1038/ki.2014.293
3. Perazella MA. Renal vulnerability to drug toxicity. Clinical Journal of the American Society of Nephrology. 2009; 4(7): 1275-1283. doi:10.2215/CJN.02050309
4. Coca SG, Singanamala S, Parikh CR. Chronic kidney disease after acute kidney injury: a systematic review and meta-analysis. Kidney International. 2012; 81(5): 442-448. doi:10.1038/ki.2011.379
5. Lucas GNC, Leitão ACC, Alencar RL, Xavier RMF, Daher EF, Silva Junior GBD. Pathophysiological aspects of nephropathy caused by non-steroidal anti-inflammatory drugs. Brazilian Journal of Nephrology. 2019; 41(1): 124-130. doi:10.1590/2175-8239-JBN-2018-0107
6. Palmer, B. F. Renal dysfunction complicating the treatment of hypertension. The New England Journal of Medicine. 2002; 347: 1256-1261. doi: 10.1056/NEJMra020676
7. Qu Y, An F, Luo Y, et al. A nephron model for study of drug-induced acute kidney injury and assessment of drug-induced nephrotoxicity. Biomaterials. 2018; 155: 41-53. doi:10.1016/j.biomaterials.2017.11.010
8. Markowitz, G. S. and Perazella MA. Drug-induced renal failure: a focus on tubulointerstitial disease. Clinica Chimica Acta, 2005; 351(1-2): 31-47. doi:10.1016/j.cccn.2004.09.005
9. Rossert J. Drug-induced acute interstitial nephritis. Kidney International. 2001; 60(2): 804-817. doi:10.1046/j.1523-1755.2001.060002804.x
10. Perazella MA. Crystal-induced acute renal failure. American Journal of Medicine. 1999; 106(4): 459-465. doi:10.1016/s0002-9343(99)00041-8
11. Cosmai L, Porta C, Ronco C, Gallieni M. Acute kidney injury in oncology and tumor Lysis syndrome. Critical Care Nephrology, 2019; 1: 234-50. doi:10.1093/ckj/sfaa127
12. Coco, T. J. and Klasner, A. E. Drug-induced rhabdomyolysis. Current opinion in pediatrics. 2004; 16: 206-210. doi:10.1097/00008480-200404000-00017
13. Pisoni, R., Ruggenenti, P. and Remuzzi, G. Drug-induced thrombotic microangiopathy: incidence, prevention, and management. Drug Safety. 2001; 24: 491-501. doi:10.2165/00002018-200124070-00002
14. Manor SM, Guillory GS, Jain SP. Clopidogrel-induced thrombotic thrombocytopenic purpura-hemolytic uremic syndrome after coronary artery stenting. Pharmacotherapy. 2004; 24(5): 664-667. doi:10.1592/phco.24.6.664.34732
15. Samah, Ahmed and Abdelhamid, Fatma and Osama, Abdalla. Effects of rosemary oil against hemato-biochemical alterations and renal oxidative damage induced by Paracetamol in rats. Annals of Veterinary and Animal Science. 2019; 6(5): 1-17. doi: 10.26609/avas.652.
16. Abdel-Zaher AO, Abdel-Hady RH, Mahmoud MM, Farrag MM. The potential protective role of alpha-lipoic acid against acetaminophen-induced hepatic and renal damage. Toxicology. 2008; 243(3): 261-270. doi:10.1016/j.tox.2007.10.010
17. Bessems JG, Vermeulen NP. Paracetamol (acetaminophen)-induced toxicity: molecular and biochemical mechanisms, analogues and protective approaches. Critical Review of Toxicology. 2001; 31(1): 55-138.
18. Gamal el-din AM, Mostafa AM, Al-Shabanah OA, Al-Bekairi AM, Nagi MN. Protective effect of arabic gum against acetaminophen-induced hepatotoxicity in mice. Pharmacological Research. 2003; 48(6): 631-635. doi:10.1016/s1043-6618(03)00226-3
19. Ghosh J, Das J, Manna P, Sil PC. Acetaminophen induced renal injury via oxidative stress and TNF-alpha production: therapeutic potential of arjunolic acid. Toxicology. 2010; 268(1-2): 8-18. doi:10.1016/j.tox.2009.11.011
20. S. Palani, S. Raja, R.Praveen Kumar, Soumya Jayakumar, B. Senthil Kumar: Therapeutic efficacy of Pimpinella tirupatiensis (Apiaceae) on acetaminophen induced nephrotoxicity and oxidative stress in male albino rats. International Journal of PharmTech Research, 2009; 1(3): 925-934.
21. H.Gulnaz, M.Tahir, B.Munir AND W. Sami. Protective effects of garlic oil on acetaminophen induced nephrotoxicity in male albino rats. Biomedical, 2010; 26: 9 – 15.
22. Surendra K. Pareta, Kartik C.Patra, Ranjeet Harwansh, Manoj Kumar, Kedar Prasad Meena. Protective Effects of Boerhaavia Diffusa Against Acetaminophen Induced ephrotoxicity in Rats. Pharmacologyonline 2; 2011: 698-706.
23. Adeneye AA, Olagunju JA, Benebo AS, Elias SO, Adisa AO, Idowu BO, Oyedeji MO et al. Nephroprotective effects of the aqueous root extract of Harungana madagas cariensis (L.) in acute and repeated dose acetaminophen renal injured rats. International Journal of Applied Research of Natural Products. 2008; 1: 6–14.
24. Kheradpezhouh E, Panjehshahin MR, Miri R, et al. Curcumin protects rats against acetaminophen-induced hepatorenal damages and shows synergistic activity with N-acetyl cysteine. European Journal of Pharmacology. 2010; 628(1-3): 274-281. doi:10.1016/j.ejphar.2009.11.027
25. Efrati S, Berman S, Siman-Tov Y, Lotan R, Averbukh Z, Weissgarten J, Golik A: N-acetylcysteine attenuates NSAID induced rat renal failure by restoring intrarenal prostaglandin synthesis. Nephrology Dialysis Transplantation. 2007; 22: 1873–1881. doi:10.1093/ndt/gfh573
26. Klaunig JE, Kamendulis LM, Hocevar BA. Oxidative stress and oxidative damage in carcinogenesis. Toxicologic Pathology. 2010; 38(1): 96-109. doi:10.1177/0192623309356453
27. Hayder M. Alkuraishy, Ali I. Al-Gareeb, and Nawar Raad Hussien: Diclofenac-induced acute kidney injury is linked with oxidative stress and pro-inflammatory changes in sprague-dawley rats. Journal of Contemporary Medical Science. 2009; 5(3): 140–144.
28. Ali Nouri, Esfandiar Heidarian: Ameliorative effects of N‐acetyl cysteine on diclofenac induced renal injury in male rats based on serum biochemical parameters, oxidative biomarkers, and histopathological study. Journal of Food Biochemistry. 2019; 43: e12950. doi:10.1111/jfbc.12950
29. Gilbert Deray: Amphotericin B nephrotoxicity. Journal of antimicrobial chemotherapy. 2002; 49(3): 37-41. doi:10.1093/jac/49.suppl_1.37
30. Cheng JT, Witty RT, Robinson RR, Yarger WE, Kennedy BM: Amphotericin B nephrotoxicity: increased renal resistance and tubule permeability. Kidney international. 1982; 22(6): 626-33. doi:10.1038/ki.1982.221
31. Schlottfeldt FD, Fernandes SM, Martins DM, Cordeiro P, Fonseca CD, Watanabe M, Vattimo MD: Prevention of amphotericin B nephrotoxicity through use of phytotherapeutic medication. Revista da Escola de Enfermagem da USP. 2015; 49: 74-9.
32. Tonomura Y, Yamamoto E, Kondo C, et al. Amphotericin B-induced nephrotoxicity: characterization of blood and urinary biochemistry and renal morphology in mice. Human and Experimental Toxicology. 2009; 28(5): 293-300. doi:10.1177/0960327109105404
33. Altuntaş A, Yılmaz HR, Altuntaş A, Uz E, Demir M, Gökçimen A, Aksu O, Bayram DŞ, Sezer MT. Caffeic acid phenethyl ester protects against amphotericin B induced nephrotoxicity in rat model. Biomed Research International. 2014; 2014: 1-8. doi: 10.1155/2014/702981
34. Yildiz C, Ozsurekci Y, Gucer S, Cengiz AB, Topaloglu R. Acute kidney injury due to acyclovir. CEN case reports. 2013; 2(1): 38-40. doi:10.1007/s13730-012-0035-0
35. Adikwu E, Kemelayefa J. Acyclovir-Induced Nephrotoxicity: The Protective Benefit of Curcumin. European Journal of Biology. 2021; 80(1): 22-8. doi: 10.26650/EurJBiol.2021.903407
36. Marwa Sayed Badawi: Evaluation of the effect of vitamin D on acyclovir-induced renal injury in adult male albino rat. South Asian Journal of Experimental Biology. 2022; 12(1): 55-63. https://doi.org/10.38150/sajeb.12(1).p55-63
37. Amir. M. Bassam, El- Sayed G. Khedr, Salah E. Mourad, Gamal. M. Aboul Hassan: the effect of Acyclovir on the kidney of albino rats; Histological and immunohistochemical study. The Egyptian Journal of Hospital Medicine. 2008; 329(1): 289-299.
38. Lu H, Han YJ, Xu JD, Xing WM, Chen J. Proteomic characterization of acyclovir-induced nephrotoxicity in a mouse model. PLoS One. 2014; 9(7): e103185. doi:10.1371/journal.pone.0103185
39. Xing W, Gu L, Zhang X, Xu J, Lu H. A metabolic profiling analysis of the nephrotoxicity of acyclovir in rats using ultra performance liquid chromatography/mass spectrometry. Environmental Toxicology and Pharmacology. 2016; 46: 234-240.
40. Mwengee W, Butler T, Mgema S, Mhina G, Almasi Y, Bradley C, Formanik JB, Rochester CG: Treatment of plague with gentamicin or doxycycline in a randomized clinical trial in Tanzania. Clinical Infectious Disease. 2006; 42: 614–621. doi:10.1086/500137
41. Mathew TH: Drug-induced renal disease. Medical Journal of Australia. 1992; 156: 724–728. doi:10.5694/j.1326-5377.1992.tb121517.x
42. Atsamo AD, Lontsie Songmene A, Metchi Donfack MF, Ngouateu OB, Nguelefack TB, Dimo T: Aqueous Extract from Cinnamomum zeylanicum (Lauraceae) Stem Bark Ameliorates Gentamicin-Induced Nephrotoxicity in Rats by Modulating Oxidative Stress and Inflammatory Markers. Evidence-Based Complementary and Alternative Medicine. 2021; 2021: 5543889. doi: 10.1155/2021/5543889.
43. Stojiljkovic N, Veljkovic S, Mihailovic D, et al. Protective effects of pentoxifylline treatment on gentamicin-induced nephrotoxicity in rats. Renal Failure. 2009; 31(1): 54-61. doi:10.1080/08860220802546321
44. Mahmoud Mohamed Said. The protective effect of eugenol against gentamicin-induced nephrotoxicity and oxidative damage in rat kidney. Fundamental and Clinical Pharmacology. 2011; 25(6): 708–716. doi:10.1111/j.1472-8206.2010.00900.x
45. Ashraf B. Abdel- Naim, Mohamed H. Abdel- Wahab, Foad F. Attia. Protective effects of Vitamin E and Probucol against Gentamicin- induced nephrotoxicity in rats. Pharmacological research. 1999; 40(2): 183-187.
46. Wu Q, Wang X, Nepovimova E, Wang Y, Yang H, Kuca K. Mechanism of cyclosporine A nephrotoxicity: Oxidative stress, autophagy, and signalings. Food and Chemical Toxicology. 2018; 118: 889-907. doi:10.1016/j.fct.2018.06.054
47. M Tutanc, V Arica, N Yılmaz, A Nacar, I Zararsiz, F Basarslan, OD Tutanc and E Nacar. Effects of erdosteine on cyclosporin-A-induced nephrotoxicity. Human and Experimental Toxicology. 2012; 31(6): 565-573. doi:10.1177/0960327111417907
48. Samy Ali Hussein, Omayam A. Ragab, Mohammed A. El- Eshmawy: Protective effect of green tea extract on Cyclosporine A: induced Nephrotoxicity in Rats. Journal of Biological Sciences. 2014; 14(4): 248-257.
49. Nguyen LT, Saad S, Shi Y, Wang R, Chou ASY, Gill A, Yao Y, Jarolimek W, Pollock CA: Lysyl oxidase inhibitors attenuate cyclosporin A-induced nephropathy in mouse. Scientific Reports. 2021; Jun 14; 11(1): 12437.
50. Vandenbussche C, Van der Hauwaert C, Dewaeles E, et al: Tacrolimus-induced nephrotoxicity in mice is associated with microRNA deregulation. Archives of Toxicology. 2018; 92(4): 1539-1550. doi:10.1007/s00204-018-2158-3
51. Park CS, Jang HJ, Lee JH, Oh MY, Kim HJ: Tetrahydro curcumin ameliorates tacrolimus-induced nephrotoxicity via inhibiting apoptosis. In Transplantation Proceedings. 2018; 50(9); 2854-2859.
52. Al-Harbi NO, Imam F, Al-Harbi MM, et al. Treatment with aliskiren ameliorates tacrolimus-induced nephrotoxicity in rats. Journal of the Renin Angiotensin Aldosterone System. 2015; 16(4): 1329-1336. doi:10.1177/1470320314530178
53. Ahmed Shaker Ali, Abdullah Saddah Almalki, Basma Tarek Alharthy: Effect of Kaempferol on Tacrolimus-Induced Nephrotoxicity and Calcineurin B1 Expression Level in Animal Model. Journal of Experimental Pharmacology. 2020; 12: 397-407. doi:10.2147/JEP.S265359
54. Luo K, Lim SW, Jin J, Jin L, Gil HW, Hwang HS, Yang CW: Cilastatin protects against tacrolimus-induced nephrotoxicity via anti-oxidative and anti-apoptotic properties. BMC nephrology. 2019; 20(1): 221. doi.10.1186/s12882-019-1399-6
55. Butani L, Afshinnik A, Johnson J, Javaheri D, Peck S, German JB, Perez RV: Amelioration of tacrolimus-induced nephrotoxicity in rats using juniper oil. Transplantation. 2003; 76(2): 306-11.
56. Willox JC, McAllister EJ, Sangster G, Kaye SB: Effects of magnesium supplementation in testicular cancer patients receiving cisplatin: a randomised trial. British Journal of Cancer. 1986; 54: 19–23. doi:10.1038/bjc.1986.147
57. Arany I, Safirstein RL. Cisplatin nephrotoxicity. Seminars in Nephrology. 2003; 23(5): 460-464. doi:10.1016/s0270-9295(03)00089-5
58. Buzzi FC, Fracasso M, Filho VC, Escarcena R, del Olmo E, San Feliciano A: New antinociceptive agents related to dihydrosphingosine. Pharmacological Reports. 2010; 62: 849–857.
59. Kawai Y, Nakao T, Kunimura N, Kohda Y, Gemba M: Relationship of intracellular calcium and oxygen radicals to cisplatin-related renal cell injury. Journal of Pharmacological Sciences. 2006; 100: 65–72. doi:10.1254/jphs.fp0050661
60. Muthuraman A, Sood S, Singla SK, Rana A, Singh A, Singh A, Singh J: Ameliorative effect of flunarizine in cisplatin-induced acute renal failure via mitochondrial permeability transition pore inactivation in rats. Naunyn Schmiedebergs Archvies of Pharmacology. 2011; 383: 57–64. doi:10.1007/s00210-010-0572-z
61. Abdel Moneim AE, Othman MS, Aref AM. Azadirachta indica attenuates cisplatin-induced nephrotoxicity and oxidative stress. Biomed Research International. 2014; 2014: 647131. doi:10.1155/2014/647131.
62. Ahmet Atessahín, Ali Osman Çeríbasi, Abdurrauf Yuce, Ozgur Bulmus and Gurkan Çikim. Basic and Clinical Pharmacology and Toxicology. 2007; 100(2): 121-126. doi:10.1111/j.1742-7843.2006.00015.x
63. Kim HJ, Park DJ, Kim JH, et al. Glutamine protects against cisplatin-induced nephrotoxicity by decreasing cisplatin accumulation. Journal of Pharmacological Sciences. 2015; 127(1): 117-126. doi:10.1016/j.jphs.2014.11.009