Main Article Content
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.
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
- Abraham P, Indirani K, Sugumar E. Effect of cyclophosphamide treatment on selected lysosomal enzymes in the kidney of rats. 2007. Pubmed Vol. 59 : 143.
- 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.
- Aroma IO. Free radicals, oxidative stress, and antioxidants in human health and disease. 1998. J Am Oil Chem Soc : 199-212.
- Barnett, S., Anthony. The Story of Rats: Their Impact on Us and Our Impact on Them. 2002. Crows Nest NSW: Allen & Unwin.
- 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.
- 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.
- 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.
- Estakhri R, Hajipour B, Majidi H, Soleimani H.Vitamin E Ameliorates Cyclophosphamide Induced Nephrotoxicity.2013.Life Science Journal : 308-311.
- Johnson, M. Labome: Laboratory Mice and Rats. 2014. The World of Laboratories.
- 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.
- Kumar S. Free radicals and antioxidants: Human and food system. Adv Appl Sci Res. 011; 2: 129-135.
- Kuehnel, W. 2003. Color Atlas of Cytology, Histology, and Microscopic Anatomy. Thiem.
- 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.
- 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.
- Mescher, AL 2013. Junqueira's Basic Histology Text and Atlas. 13th ed. McGraw-Hill Primis: 851-871.
- 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.
- Naughton CA, . Drug-induced nephrotoxicity. 2008. Am Fam Physician Vol. 78 : 743-750.
- Nermin, M, Yusiff. 2018. Vitamin C. Periodontology Department : 1-29.
- 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.
- 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.
- Ramaswamy S, Pathak H, Ravindran V. 2019. Safety of Cyclophosphamide Therapy in Autoimmune Rheumatice disease. Indian Journal of Rheumatology : 1-7.
- Sharp, P., Villano, J. 2012. The Laboratory Rat. CRC Press. US
- Sirois, M. 2005. Laboratory Animal Medicine: Principles and Procedures. United States of America: Mosby Inc.
- Sloane, E. 2003. Anatomy and Physiology for Beginners. Translation by Palupi Widyastuti. Jakarta: EGC Medical Book : 318-319.
- Suckow, MA, Steven, HW, Craig, LF 2006. The Laboratory Rat. 2nd Edition. California (USA): Academic Pr.
- Sweetman, SC. 2009. Martindale the Complete Drug Reference. The Pharmaceutical Press: Chicago Vol. 36. 80-81.
- 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
- Velisek J, Cejpek K. 2007. Biosynthesis of food constituents: Vitamins. Water-soluble vitamins, part 2—A review. Czech Journal of Food Science : 40-45.
- Wahyuni, E, Kumorowati, P, Suardi, S, Yunus M. Guidebook for Pathology Laboratory Work, ed.2. 2012. Maros Veterinary Center. Makassar.
- Wistar Institute. 2016. Our History Philadelphia: The Wistar Institute.
- Zhang J, Tian Q, Zhou F.. Clinical Pharmacology of Cyclophosphamide and Ifosfamide. Current Drug Therapy. 2016. Vol. 1: 55-85.