Skip to content
2000
Volume 17, Issue 3
  • ISSN: 2589-9775
  • E-ISSN: 2589-9783

Abstract

Cyclophosphamide is a drug derived from nitrogenous mustards and is mainly indicated for the anti-neoplastic clinic. When it is metabolized in the liver, it produces acrolein, a cytotoxic metabolite capable of generating damage to the body. The oxidative, nitrative and nitrosative stress are responsible for mediating this side effect since the toxicity of the drug induces the production of reactive species of oxygen (ROS) and nitrogen (RNS). These radicals are unstable and react with other molecules that can result in cellular lesions such as lipid peroxidation, enzymatic inactivation, and excessive activation of pro-inflammatory genes, producing molecules such as malonaldehyde (MDA) and nitric oxide (NO), representing oxidative stress markers. One of the consequences of these mechanisms is nephrotoxicity. In contrast, some compounds have direct or indirect antioxidante action, which are the objects of this study: gallic acid, aminoguanidine, chrysin, hesperidine, naringin, morin-5'-sulfonic acid sodium salt and spirulina. All of them are responsible for the nephroprotective activity when administered during experiments or . Thus, this observational bibliographic research is characterized as qualitative descriptive and explanatory, since it focuses on analyzing the antioxidant properties of compounds with possible potentials to inhibit the nephrotoxicity induced by cyclophosphamide and describe the results, in addition to clarifying the biochemical activities involved in the process.

© 2025 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/cdrr/10.2174/0125899775296035240910075130
2024-09-19
2025-09-18

  • From This Site

    /content/journals/cdrr/10.2174/0125899775296035240910075130
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. IqubalA. IqubalM.K. SharmaS. AnsariM.A. NajmiA.K. AliS.M. AliJ. HaqueS.E. Molecular mechanism involved in cyclophosphamide-induced cardiotoxicity: Old drug with a new vision.Life Sci.201921811213110.1016/j.lfs.2018.12.01830552952
     [Google Scholar]
  2. MogheA. GhareS. LamoreauB. MohammadM. BarveS. McClainC. Joshi-BarveS. Molecular mechanisms of acrolein toxicity: relevance to human disease.Toxicol. Sci.2015143224225510.1093/toxsci/kfu23325628402
     [Google Scholar]
  3. Instituto Nacional do Câncer (Ministério da Saúde)2019Available from:https://www.inca.gov.br/o-que-e-cancer(accessed on 23-8-2024)
  4. Pan American Organization of Health (PAHO).2020Available from:https://www.paho.org/bra/index.php?option=com_content&view=article&id=5588:folha-informativa-cancer&Itemid=1094#:~:text=O%20c%C3%A2ncer%20%C3%A9%20uma%20das,2%2C09%20milh%C3%B5es%20de%20casos(accessed on 20-8-2024)
  5. PolavarapuA. StillabowerJ.A. StubblefieldS.G.W. TaylorW.M. BaikM.H. The mechanism of guanine alkylation by nitrogen mustards: a computational study.J. Org. Chem.201277145914592110.1021/jo300351g22681226
     [Google Scholar]
  6. CunhaA.L. MouraK.S. BarbosaJ.C. SantosA.F. Fundamentos químicos da ação dos radicais no organismo.Diversitas J.20161181310.17648/diversitas‑journal‑v1i1.450
     [Google Scholar]
  7. CeronC. MarchiK. MunizJ. TirapelliC. Vascular oxidative stress: a key factor in the development of hypertension associated with ethanol consumption.Curr. Hypertens. Rev.201510421322210.2174/15734021100415031912273625801625
     [Google Scholar]
  8. RabêloL.A. SouzaV.N. FonsecaL.J.S. SampaioW.O. Desbalanço redox: NADPH oxidase como um alvo terapêutico no manejo cardiovascular.Arq. Bras. Cardiol.201094568469310.1590/S0066‑782X201000050001820549031
     [Google Scholar]
  9. AntunesM.V. LazzarettiC. GamaroG.D. LindenR. Estudo pré-analítico e de validação para determinação de malondialdeído em plasma humano por cromatografia líquida de alta eficiência, após derivatização com 2,4-dinitrofenilhidrazina.RBCF Rev. Bras. Cienc. Farm.200844227928710.1590/S1516‑93322008000200013
     [Google Scholar]
  10. SilvaW.J.M. FerrariC.K.B. Metabolismo mitocondrial, radicais livres e envelhecimento.Rev. Bras. Geriatr. Gerontol.201114344145110.1590/S1809‑98232011000300005
     [Google Scholar]
  11. OgunsanwoO.R. OyagbemiA.A. OmobowaleT.O. AsenugaE.R. SabaA.B. Biochemical and electrocardiographic studies on the beneficial effects of gallic acid in cyclophosphamide-induced cardiorenal dysfunction.J. Complement. Integr. Med.20171432016016110.1515/jcim‑2016‑016128333655
     [Google Scholar]
  12. BaharmiS. KalantariH. KalantarM. GoudarziM. MansouriE. KalantarH. Pretreatment with gallic acid mitigates cyclophosphamide induced inflammation and oxidative stress in mice.Curr. Mol. Pharmacol.202115120421234061011
     [Google Scholar]
  13. ShokzadehM. Ghassemi-BarghiN. Antioxidant and genoprotective effects of amifostine against irinotecan toxicity in human hepatoma cells.Int. J. Cancer Res. Ther.2018315
     [Google Scholar]
  14. StankiewiczA. SkrzydlewskaE. Protection against cyclophosphamide-induced renal oxidative stress by amifostine: the role of antioxidative mechanisms.Toxicol. Mech. Methods200313430130810.1080/71385719120021155
     [Google Scholar]
  15. ThornalleyP.J. Use of aminoguanidine (Pimagedine) to prevent the formation of advanced glycation endproducts.Arch. Biochem. Biophys.20034191314010.1016/j.abb.2003.08.01314568006
     [Google Scholar]
  16. AbrahamP. RabiS. Nitrosative stress, protein tyrosine nitration, PARP activation and NAD depletion in the kidneys of rats after single dose of cyclophosphamide.Clin. Exp. Nephrol.200913428128710.1007/s10157‑009‑0160‑z19266253
     [Google Scholar]
  17. TemelY. KucuklerS. YıldırımS. CaglayanC. KandemirF.M. Protective effect of chrysin on cyclophosphamide-induced hepatotoxicity and nephrotoxicity via the inhibition of oxidative stress, inflammation, and apoptosis.Naunyn Schmiedebergs Arch. Pharmacol.2020393332533710.1007/s00210‑019‑01741‑z31620822
     [Google Scholar]
  18. DeviH.P. MazumderP.B. DeviL.P. Antioxidant and antimutagenic activity of Curcuma caesia Roxb. rhizome extracts.Toxicol. Rep.2015242342810.1016/j.toxrep.2014.12.01828962377
     [Google Scholar]
  19. MazumderP.B. DeviH.P. Methanolic Extract of Curcuma caesia Roxb. prevents the toxicity caused by Cyclophosphamide to bone marrow cells, liver and kidney of mice.Pharmacognosy Res.201681434910.4103/0974‑8490.17110626941535
     [Google Scholar]
  20. AbrahamP. IsaacB. The effects of oral glutamine on cyclophosphamide-induced nephrotoxicity in rats.Hum. Exp. Toxicol.201130761662310.1177/096032711037655220621952
     [Google Scholar]
  21. CruzatV. Macedo RogeroM. Noel KeaneK. CuriR. NewsholmeP. Glutamine: Metabolism and Immune Function, Supplementation and Clinical Translation.Nutrients20181011156410.3390/nu1011156430360490
     [Google Scholar]
  22. Mas-CapdevilaA. TeichenneJ. Domenech-CocaC. CaimariA. Del BasJ.M. EscotéX. CrescentiA. Effect of Hesperidin on Cardiovascular Disease Risk Factors: The Role of Intestinal Microbiota on Hesperidin Bioavailability.Nutrients2020125148810.3390/nu1205148832443766
     [Google Scholar]
  23. FouadA.A. Al-MulhimA.S. JresatI. Cannabidiol treatment ameliorates ischemia/reperfusion renal injury in rats.Life Sci.2012917-828429210.1016/j.lfs.2012.07.03022877651
     [Google Scholar]
  24. Cipolla-NetoJ. AmaralF.G. Melatonin as a Hormone: New Physiological and Clinical Insights.Endocr. Rev.2018396990102810.1210/er.2018‑0008430215696
     [Google Scholar]
  25. GoudarziM. KhodayarM.J. Hosseini TabatabaeiS.M.T. GhaznaviH. FatemiI. MehrzadiS. Pretreatment with melatonin protects against cyclophosphamide‐induced oxidative stress and renal damage in mice.Fundam. Clin. Pharmacol.201731662563510.1111/fcp.1230328692163
     [Google Scholar]
  26. MandaK. BhatiaA.L. Prophylactic action of melatonin against cyclophosphamide-induced oxidative stress in mice.Cell Biol. Toxicol.200319636737210.1023/B:CBTO.0000013342.17370.1615015761
     [Google Scholar]
  27. CaglayanC. TemelY. KandemirF.M. YildirimS. KucuklerS. Naringin protects against cyclophosphamide-induced hepatotoxicity and nephrotoxicity through modulation of oxidative stress, inflammation, apoptosis, autophagy, and DNA damage.Environ. Sci. Pollut. Res. Int.20182521209682098410.1007/s11356‑018‑2242‑529766429
     [Google Scholar]
  28. RomaniA. IeriF. UrciuoliS. NoceA. MarroneG. NedianiC. BerniniR. Health Effects of Phenolic Compounds Found in Extra-Virgin Olive Oil, By-Products, and Leaf of Olea europaea L.Nutrients2019118177610.3390/nu1108177631374907
     [Google Scholar]
  29. ALHaithloulH.A.S. AlotaibiM.F. Bin-JumahM. ElgebalyH. MahmoudA.M. Olea europaea leaf extract up-regulates Nrf2/ARE/HO-1 signaling and attenuates cyclophosphamide-induced oxidative stress, inflammation and apoptosis in rat kidney.Biomed. Pharmacother.201911167668510.1016/j.biopha.2018.12.11230611992
     [Google Scholar]
  30. BraakhuisA. Evidence on the Health Benefits of Supplemental Propolis.Nutrients20191111270510.3390/nu1111270531717277
     [Google Scholar]
  31. El-NaggarS.A. Alm-EldeenA.A. GermoushM.O. El-BorayK.F. ElgebalyH.A. Ameliorative effect of propolis against cyclophosphamide-induced toxicity in mice.Pharm. Biol.201553223524110.3109/13880209.2014.91423025289525
     [Google Scholar]
  32. El-SheikhA.A. MorsyM.A. OkashaA.M. Inhibition of NF-κB/TNF-α pathway may be involved in the protective effect of resveratrol against cyclophosphamide-induced multi-organ toxicity.Immunopharmacol. Immunotoxicol.201739418018710.1080/08923973.2017.131891328463035
     [Google Scholar]
  33. Merwid-LądA. TrochaM. ChlebdaE. SozańskiT. MagdalanJ. KsiądzynaD. KopaczM. KuźniarA. NowakD. PieśniewskaM. Fereniec-GołębiewskaL. KwiatkowskaJ. SzelągA. Effects of morin-5′-sulfonic acid sodium salt (NaMSA) on cyclophosphamide-induced changes in oxido-redox state in rat liver and kidney.Hum. Exp. Toxicol.201231881281910.1177/096032711143109022241626
     [Google Scholar]
  34. KiełczykowskaM. KocotJ. PaździorM.A.R.E.K. MusikI. Selenium – a fascinating antioxidant of protective properties.Adv. Clin. Exp. Med.201827224525510.17219/acem/6722229521069
     [Google Scholar]
  35. GunesS. SahinturkV. UsluS. AyhanciA. KacarS. UyarR. Protective Effects of Selenium on Cyclophosphamide-Induced Oxidative Stress and Kidney Injury.Biol. Trace Elem. Res.2018185111612310.1007/s12011‑017‑1231‑829290051
     [Google Scholar]
  36. GrosshagauerS. KraemerK. SomozaV. The true value of spirulina.J. Agric. Food Chem.202068144109411510.1021/acs.jafc.9b0825132133854
     [Google Scholar]
  37. SinanogluO. YenerA.N. EkiciS. MidiA. AksungarF.B. The protective effects of spirulina in cyclophosphamide induced nephrotoxicity and urotoxicity in rats.Urology20128061392.e11392.e610.1016/j.urology.2012.06.05322951000
     [Google Scholar]
/content/journals/cdrr/10.2174/0125899775296035240910075130
Loading
Antioxidant and Cytoprotective Effects of Different Compounds on Cyclophosphamide-induced Nephrotoxicity
Current Drug Research Reviews 17, 352 (2025); https://doi.org/10.2174/0125899775296035240910075130
/content/journals/cdrr/10.2174/0125899775296035240910075130
/content/journals/cdrr/10.2174/0125899775296035240910075130
Loading

Data & Media loading...


  • Article Type:     Review Article
Keyword(s): Antioxidants; cyclophosphamide; malonaldehyde; nephrotoxicity; oxidative stress; reactive species of oxygen

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test