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Abstract

Background: Cyclophosphamide (CPD) causes renal cell toxicity due to its toxic metabolites. Objectives: This study aimed to evaluate the nephroprotective effect of vitamin C at 125 mg/kgBW, 250 mg/kgBW, and 500 mg/kgBW doses based on the biomarker level of urea, creatinine, parameter of urinalysis and renal histopathology. Material and Methods: The experimental animals consisted of 25 rats (Rattus norvegicus) that were divided into 5 treatment groups: healthy control, placebo (water for injection + CPD 250mg/kgBB), and 3 vitamin C treatment groups (125, 250, or 500 mg/kgBW + CPD 250mg/kgBB). Results: The results of blood biomarker, urine analysis, and histopathological analysis showed that CPD induced nephrotoxicity characterized by an increase in urea levels from 21.79 mg/l to 156.65 mg/l, creatinine from 0.375 to 0.717 mg/l, urine protein from 0 to 2.7, with histopathological damage scores from mild to severe (scores 1-3). In the treatment groups, the average damage score was 1-2 (mild score). However, of the three doses used, only the 500 mg/kg dose had significantly improved biomarkers compared to the placebo group, including the urea, creatinine, and urine protein levels, as well as histopathological scores (p<0.05). Conclusions: Vitamin C at a dose of 250 mg/kgBW was able to prevent the increase of urea, creatinine, and urine protein levels, however, a higher dose (500 mg/kg) was required to provide optimal protection against renal structural damage caused by cyclophosphamide.

Keywords

Creatinine Urea Nephrotoxicity Urine protein Cyclophosphamide Vitamin C

Article Details

How to Cite
Dwi Yulianti, A., Djabir, Y. Y., & Prihantono, P. (2023). Vitamin C elicits protection against cylophosphamide-induced nephrotoxicity in rat animal model: Vitamin C Memproteksi Terhadap Nefrotoksisitas Yang Diinduksi Siklofosfamid Pada Hewan Model Tikus. Jurnal Farmasi Galenika (Galenika Journal of Pharmacy) (e-Journal), 9(1), 55-70. https://doi.org/10.22487/j24428744.2023.v9.i1.15992

References

  1. Abraham P, Indirani K, Sugumar E. Effect of cyclophosphamide treatment on selected lysosomal enzymes in the kidney of rats. 2007. Pubmed Vol. 59 : 143.
  2. Antunes , Lusaˆnia M. Greggi Antunes, et al. 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, 2000: 405-409.
  3. Aroma IO. Free radicals, oxidative stress, and antioxidants in human health and disease. 1998. J Am Oil Chem Soc : 199-212.
  4. Barnett, S., Anthony. The Story of Rats: Their Impact on Us and Our Impact on Them. 2002. Crows Nest NSW: Allen & Unwin.
  5. Bhat N, Kalthur GS, Padmashali S, Monappa V. 2018. Toxic Effects of Different Doses of Cyclophosphamide on Liver and Kidney Tissue in Swiss Albino Mice: A Histopathological Study. Ethiop J Sci.28(6):711.
  6. Djabir YY, Usmar, Elly Wahyudin, Sukamto, Ika Reskia, Dila Paramitha, Irma Alia. 2016. Roles of Vitamin C and Vitamin E on Doxorubicin – Induced Renal and Liver Toxicities in Rats. Nusantara Medical Science Journal.1:16-20.
  7. Elmore A. Final report of the safety assessment of l-ascorbic acid, calcium ascorbate, magnesium ascorbate, magnesium ascorbyl phosphate, sodium ascorbate, and sodium ascorbyl phosphate as used in cosmetics. 2005. International Journal of Toxicology Vol. 24 : 51-111.
  8. Estakhri R, Hajipour B, Majidi H, Soleimani H.Vitamin E Ameliorates Cyclophosphamide Induced Nephrotoxicity.2013.Life Science Journal : 308-311.
  9. Johnson, M. Labome: Laboratory Mice and Rats. 2014. The World of Laboratories.
  10. Kennedy, Groepper D, Tagen M, Christensen R, Navid F, Gajjar A. Stability of cyclophosphamide in extemporaneous oral suspensions. 2010. Ann Pharmacother Vol. 44 : 295-301.
  11. Kumar S. Free radicals and antioxidants: Human and food system. Adv Appl Sci Res. 011; 2: 129-135.
  12. Kuehnel, W. 2003. Color Atlas of Cytology, Histology, and Microscopic Anatomy. Thiem.
  13. Lawson M, Vasilaras A, De Vries A, et al.. Urological implications of cyclophosphamide and ifosfamide. 2008. Scand J Urol Nephrol. Vol. 42(4) : 309-317.
  14. Muneb U, Rehman, Mir T, Farrah A, Qamar W, Latieef A, et al. Cyclophosphamide-induced nephrotoxicity, genotoxicity, and damage in kidney genomic DNA of Swiss albino mice: the protective effect of Ellagic acid. 2012.Molecular and Cellular Biochemistryvolumes 365: 119–127.
  15. Mescher, AL 2013. Junqueira's Basic Histology Text and Atlas. 13th ed. McGraw-Hill Primis: 851-871.
  16. Monika S, Kumar N, Garg V, Anjana, Jyoti D. 2014. A Review on Renal Protective Agents for Cyclophosphamide Induced Nephrotoxicity. World Journal of Pharmacy and Pharmaceutical Sciences Vol 3: 737-747.
  17. Naughton CA, . Drug-induced nephrotoxicity. 2008. Am Fam Physician Vol. 78 : 743-750.
  18. Nermin, M, Yusiff. 2018. Vitamin C. Periodontology Department : 1-29.
  19. Nurlina, Estuningsih S, Sugito, Masyitha D. 2014. Intestinal Microbial Stability, Liver and Kidney Histology of Mice After Administration of Pliek Extract u. Indonesian Venterinary Journal : 370-379.
  20. Panigrahy SK, Jatawa S, Tiwari A. 2011. Therapeutic use of cyclophosphamide and its cytotoxic action: A challenge for researchers. Journal of Pharmacy Research : 2755-2757.
  21. Ramaswamy S, Pathak H, Ravindran V. 2019. Safety of Cyclophosphamide Therapy in Autoimmune Rheumatice disease. Indian Journal of Rheumatology : 1-7.
  22. Sharp, P., Villano, J. 2012. The Laboratory Rat. CRC Press. US
  23. Sirois, M. 2005. Laboratory Animal Medicine: Principles and Procedures. United States of America: Mosby Inc.
  24. Sloane, E. 2003. Anatomy and Physiology for Beginners. Translation by Palupi Widyastuti. Jakarta: EGC Medical Book : 318-319.
  25. Suckow, MA, Steven, HW, Craig, LF 2006. The Laboratory Rat. 2nd Edition. California (USA): Academic Pr.
  26. Sweetman, SC. 2009. Martindale the Complete Drug Reference. The Pharmaceutical Press: Chicago Vol. 36. 80-81.
  27. Syafhan, NF 2009. TAC (Docetaxel-Doxorubicin-Cyclophosphamide) and FAC (Fluorouracil-Doxorubicin-Cyclophosphamide) regimens in breast cancer patients at Dharmais Cancer Hospital Jakarta Medical Data Analysis 2007-2008. 2009. Jakarta: University of Indonesia
  28. Velisek J, Cejpek K. 2007. Biosynthesis of food constituents: Vitamins. Water-soluble vitamins, part 2—A review. Czech Journal of Food Science : 40-45.
  29. Wahyuni, E, Kumorowati, P, Suardi, S, Yunus M. Guidebook for Pathology Laboratory Work, ed.2. 2012. Maros Veterinary Center. Makassar.
  30. Wistar Institute. 2016. Our History Philadelphia: The Wistar Institute.
  31. Zhang J, Tian Q, Zhou F.. Clinical Pharmacology of Cyclophosphamide and Ifosfamide. Current Drug Therapy. 2016. Vol. 1: 55-85.