Development rat models of nephrotoxic: A pre-clinical test model to discover nephroprotective agents
DOI:
https://doi.org/10.46542/pe.2024.242.6370Keywords:
Cisplatin, Doxorubicin, Gentamicin, Nephrotoxic model, RatAbstract
Background: The use of drugs, including aminoglycoside drugs and anticancer drugs, is one of the things that can cause toxicity to the kidneys. Therefore, the development of agents that function as nephroprotectors continues to be researched.
Objective: This study aims to obtain a nephrotoxic experimental animal model for testing nephroprotective agents.
Method: The treatment was normal group, groups given a single dose of Cisplatin 7 mg/kgBW i.p (Cis), Doxorubicin single dose 25 mg/kgBW i.p (Dox-25), Doxorubicin repeated dose 4 mg/kgBW i.p twice/week for two weeks (Dox-4 repeated dose), and Gentamicin single dose 112 mg/kgBW i.p (Gen). The nephrotoxic effect was assessed by the parameters of kidney weight ratio, Ureum, Creatinine and Albumin levels in rat serum.
Result: The nephrotoxic effect was indicated by an increase in the renal weight ratio of the Cisplatin; Dox-25, Dox-4 repeated, and Gen groups than normal, respectively. There was an increase in serum BUN levels, an increase in serum creatinine, and a decrease in serum albumin levels compared to the normal group.
Conclusion: Cisplatin, Doxorubicin and Gentamicin have nephrotoxic effects. The administration of a single dose of cisplatin at 7 mg/kg BW gave the strongest nephrotoxic effect, making it appropriate as a model of acute nephrotoxicity in rats.
References
Altınkaynak, Y., Kural, B., Akcan, B. A., Bodur, A., Özer, S., Yuluğ, E., Munğan, S., Kaya, C., & Örem, A. (2018). Protective effects of L-theanine against doxorubicin-induced nephrotoxicity in rats. Biomedicine & Pharmacotherapy, 108, 1524–1534. https://doi.org/10.1016/j.biopha.2018.09.171
Amarasiri, S. S., Attanayake, A. P., Mudduwa, L. K. B., & Jayatilaka, K. A. P. W. (2022). Doxorubicin-induced nephrotoxicity model in Wistar rats: Characterization of biochemical parameters, histological and immunohistochemical assessment. Ceylon Journal of Science, 51(4), 471–479. https://doi.org/10.4038/cjs.v51i4.8064
An, P., Dong, S., Li, X., Cai, Z., Ye, B., Zhang, A., Shi, X., & Wu, X. (2020). Wenyang huazhuo fang exerts transient receptor potential cation channel subfamily C member-dependent nephroprotection in a rat model of doxorubicin-induced nephropathy. Journal of Traditional Chinese Medicine, 40(4), 613–620. https://doi.org/10.19852/j.cnki.jtcm.2020.04.010
Arunachalam, S., Nagoor Meeran, M. F., Azimullah, S., Kumar Jha, N., Saraswathiamma, D., Albawardi, A., Beiram, R., & Ojha, S. (2022). α-Bisabolol attenuates NF-κB/MAPK signaling activation and ER-stress-mediated apoptosis by invoking Nrf2-mediated antioxidant defense systems against doxorubicin-induced testicular toxicity in rats. Nutrients, 14(21), 4648. https://doi.org/10.3390/nu14214648v
Brown, A., Kumar, S., & Tchounwou, P. B. (2019). Cisplatin-Based Chemotherapy of Human Cancers. Journal of cancer science & therapy, 11(4), 97. https://pubmed.ncbi.nlm.nih.gov/32148661/
Gamaan, M. A., Zaky, H. S., & Ahmed, H. I. (2023). Gentamicin-induced nephrotoxicity: A mechanistic approach. Azhar International Journal of Pharmaceutical and Medical Sciences, 3(2), 11–19. https://doi.org/10.21608/aijpms.2023.161755.1167
Hu, H., Xie, C., Weng, Z., Yu, P., Wang, Y., & Shan, L. (2022). Dexrazoxane alleviated doxorubicin-induced nephropathy in rats. Pharmacology, 107(3–4), 206–215. https://doi.org/10.1159/000521220
Huang, H., Jin, W., Huang, M., Ji, H., Capen, D. E., Xia, Y., Yuan, J., Păunescu, T. G., & Lu, H. A. J. (2020). Gentamicin-induced acute kidney injury in an animal model involves programmed necrosis of the collecting duct. Journal of the American Society of Nephrology, 31(9), 2097. https://doi.org/10.1681/ASN.2019020204
Jafari, F., & Elyasi, S. (2021). Prevention of colistin induced nephrotoxicity: A review of preclinical and clinical data. Expert Review of Clinical Pharmacology, 14(9), 1113–1131. https://doi.org/10.1080/17512433.2021.1933436
Li, A., Zhang, W., Zhang, L., Liu, Y., Li, K., Du, G., & Qin, X. (2020a). Elucidating the time-dependent changes in the urinary metabolome under doxorubicin-induced nephrotoxicity. Toxicology Letters, 319, 204–212. https://doi.org/10.1016/j.toxlet.2019.11.020
Li, X., Zheng, S., & Wu, G. (2020b). Amino acid metabolism in the kidneys: Nutritional and physiological significance. In G. Wu (eds), Amino acids in nutrition and health (pp. 71–95). Advances in Experimental Medicine and Biology, vol 1265. Springer, Cham. https://doi.org/10.1007/978-3-030-45328-2_5
McMahon, K. R., Rassekh, S. R., Schultz, K. R., …, Zappitelli, M. (2020). Epidemiologic characteristics of acute kidney injury during cisplatin infusions in children treated for cancer. JAMA network open, 3(5), e203639. https://doi.org/10.1001%2Fjamanetworkopen.2020.3639
McSweeney, K. R., Gadanec, L. K., Qaradakhi, T., Ali, B. A., Zulli, A., & Apostolopoulos, V. (2020). Mechanisms of cisplatin-induced acute kidney injury: Pathological mechanisms, pharmacological interventions, and genetic mitigations. Cancers, 13(7), 1572. https://doi.org/10.3390/cancers13071572
Naji Ebrahimi Yazd, Z., Hosseinian, S., Shafei, M. N., Ebrahimzadeh Bideskan, A., Entezari Heravi, N., Parhizgar, S., Shahraki, S., Samadi Noshahr, Z., Mahzari, S., & Khajavi Rad, A. (2018). Protection against doxorubicin-induced nephropathy by plantago major in Rat. Iranian journal of kidney diseases, 12(2), 99–106. https://pubmed.ncbi.nlm.nih.gov/29507272/
Negi, K., & Mirza, A. (2020). Nephroprotective and therapeutic potential of traditional medicinal plants in renal diseases. Journal of Drug Research in Ayurvedic Sciences, 5(3), 177–185. http://dx.doi.org/10.5005/jdras-10059-0079
Perazella, M. A., & Shirali, A. C. (2018). Nephrotoxicity of cancer immunotherapies: Past, present and future. Journal of the American Society of Nephrology, 29(8), 2039. https://doi.org/10.1681/asn.2018050488
Petejova, N., Martinek, A., Zadrazil, J., Kanova, M., Klementa, V., Sigutova, R., Kacirova, I., Hrabovsky, V., Svagera, Z., & Stejskal, D. (2019). Acute kidney injury in septic patients treated by selected nephrotoxic antibiotic agents—Pathophysiology and biomarkers—A Review. International Journal of Molecular Sciences, 21(19), 7115. https://doi.org/10.3390/ijms21197115
Salman, S., Nur Darmawan, S. A., Elyyana , N., Khairunnisa , S., Pratama , A. A., & Nurayuni , T. (2023). The effect of syrup fever drug content on cases of acute kidney failure in children. Journal of Pharmaceutical and Sciences, 6(2), 451–455. http://dx.doi.org/10.36490/journal-jps.com.v6i2.94
Sandhiutami, N. M. D., Arozal, W., Louisa, M., Rahmat, D., Mandy, T. (2019). Comparative effect of curcumin and nanocurcumin on nephroprotection at cisplatin-induced rats. Journal of Pharmacy & Bioallied Sciences, 11(Suppl 4), S567. https://doi.org/10.4103/jpbs.jpbs_208_19
Toale, K.M., Johnson, T.N., Ma, M.Q., & Vu, N.H. (2021). Chemotherapy Toxicities. In K. H. Todd, C.R. Thomas Jr., & K. Alagappan (eds), Oncologic emergency medicine (pp. 637–661). Springer, Cham. https://doi.org/10.1007/978-3-030-67123-5_48
Udupa, V., & Prakash, V. (2019). Gentamicin induced acute renal damage and its evaluation using urinary biomarkers in rats. Toxicology reports, 6, 1–99. https://doi.org/10.1016/j.toxrep.2018.11.015