Molecular and Cellular Biochemistry

, Volume 440, Issue 1–2, pp 139–145 | Cite as

Cisplatin-induced human peripheral blood mononuclear cells’ oxidative stress and nephrotoxicity in head and neck cancer patients: the influence of hydrogen peroxide

  • Júlia C. F. Quintanilha
  • Marília B. Visacri
  • Vanessa M. Sousa
  • Larissa B. Bastos
  • Camila O. Vaz
  • João P. O. Guarnieri
  • Laís S. Amaral
  • Carina Malaguti
  • Carmen S. P. Lima
  • Anibal E. Vercesi
  • Patricia Moriel
Article
  • 104 Downloads

Abstract

Cisplatin is a widely used antineoplastic agent in the treatment of head and neck cancer. However, it is highly nephrotoxic. Oxidative stress is the main mechanism responsible for cisplatin-induced nephrotoxicity. The aim of this study was to characterize cisplatin-induced nephrotoxicity, oxidative stress in peripheral blood mononuclear cells, and the relationship between them. Twenty-four patients were included in the study. Patients had their blood collected prior to cisplatin administration, and 5 and 20 days after initiating therapy, to assess renal function and to determine oxidative stress with MitoSOX™Red, H2DCF-DA, and Amplex® Red tests. Renal function was assessed by measuring serum creatinine, creatinine clearance, and blood urea nitrogen (BUN). Serum creatinine and creatinine clearance were used to grade nephrotoxicity using Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Compared to baseline values, the mean BUN and serum creatinine increased 135 and 100%, respectively, 5 days after cisplatin infusion. Mean creatinine clearance showed a 43% decrease compared to baseline value. Non-statistically significant changes in superoxide anion (O 2 •− ), hydrogen peroxide (H2O2), and general reactive oxygen species production occurred. A higher production of H2O2 was correlated with variation in serum creatinine, and was associated with higher grades for serum creatinine increases and creatinine clearance reductions. Linear regression analyses showed an association between H2O2 production and serum creatinine, creatinine clearance, and BUN levels. These results were observed for 5 days following cisplatin administration. In conclusion, H2O2 production was significantly related to changes in all renal parameters that were evaluated, following the cisplatin infusion.

Keywords

Cisplatin Nephrotoxicity Oxidative stress Hydrogen peroxide Head and neck cancer 

Notes

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflicts of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

References

  1. 1.
    Miller RP, Tadagavadi RK, Ramesh G, Reeves WB (2010) Mechanisms of cisplatin nephrotoxicity. Toxins (Basel) 2:2490–2518CrossRefGoogle Scholar
  2. 2.
    Saleh S, El-Demerdash E (2005) Protective effects of l-arginine against cisplatin-induced renal oxidative stress and toxicity: role of nitric oxide. Basic Clin Pharmacol Toxicol 97:91–97CrossRefPubMedGoogle Scholar
  3. 3.
    Faig J, Haughton M, Taylor RC et al (2016) Retrospective analysis of cisplatin nephrotoxicity in patients with head and neck cancer receiving outpatient treatment with concurrent high-dose cisplatin and radiotherapy. Am J Clin Oncol. doi: 10.1097/COC.0000000000000301 PubMedPubMedCentralGoogle Scholar
  4. 4.
    Chirino YI, Pedraza-Chaverri J (2009) Role of oxidative and nitrosative stress in cisplatin-induced nephrotoxicity. Exp Toxicol Pathol 61:223–242CrossRefPubMedGoogle Scholar
  5. 5.
    Karnofsky DA, Burchenal JH (1949) The evaluation of therapeutics in cancer. In: Macleod CM (ed) Evaluation of chemotherapeutic agents. Columbia University Press, New York, pp 191–205Google Scholar
  6. 6.
    Jindal SK, Malik SK, Dhand R, Gujral JS, Malik AK, Datta BN (1982) Bronchogenic carcinoma in Northern India. Thorax 37:343–347CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Whitcomb DC, Yadav D, Adam S et al (2008) Multicenter approach to recurrent acute and chronic pancreatitis in the United States: the North American Pancreatitis Study 2 (NAPS2). Pancreatology 8:520–531CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Edge S, Compton CC (2010) The American Joint Committee on Cancer: the 7th edition of the AJCC cancer staging manual and the future of TNM. Ann Surg Oncol 17:1471–1474Google Scholar
  9. 9.
    Boyum A (1968) Separation of leukocytes from blood and bone marrow. Scand J Clin Lab Invest 21:77CrossRefGoogle Scholar
  10. 10.
    Ferranti R, da Silva MM, Kowaltowski AJ (2003) Mitochondrial ATP-sensitive K+ channel opening decreases reactive oxygen species generation. FEBS Lett 536:51–55CrossRefPubMedGoogle Scholar
  11. 11.
    Payne CM, Weber C, Crowley-Skillicorn C et al (2007) Deoxycholate induces mitochondrial oxidative stress and activates NF-kappaB through multiple mechanisms in HCT-16 colon epithelial cells. Carcinogenesis 28:215–222Google Scholar
  12. 12.
    Ali SF, LeBel CP, Bondy SC (1992) Reactive oxygen species formation as a biomarker of methylmercury and trimethyltin neurotoxicity. Neurotoxicology 13:637–648PubMedGoogle Scholar
  13. 13.
    Karlsson M, Kurz T, Brunk UT, Nilsson SE, Frennesson CI (2010) What does the commonly used DCF test for oxidative stress really show? Biochem J 428:183–190CrossRefPubMedGoogle Scholar
  14. 14.
    Cockcroft DW, Gault MH (1976) Prediction of creatinine clearance from serum creatinine. Nephron 16:31–41CrossRefPubMedGoogle Scholar
  15. 15.
    US Department of Health and Human Services (2010) Common Terminology Criteria for Adverse Events (CTCAE). US Department of Health and Human Services, National Institutes of Health, National Cancer Institute, Version 4.0Google Scholar
  16. 16.
    Santos NA, Catão CS, Martins NM, Curti C, Bianchi ML, Santos AC (2007) Cisplatin-induced nephrotoxicity is associated with oxidative stress, redox state unbalance, impairment of energetic metabolism and apoptosis in rat kidney mitochondria. Arch Toxicol 81:495–504CrossRefPubMedGoogle Scholar
  17. 17.
    Marullo R, Werner E, Degtyareva N et al (2013) Cisplatin induces a mitochondrial-ROS response that contributes to cytotoxicity depending on mitochondrial redox status and bioenergetic functions. PLoS ONE 8:e81162CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Waseem M, Bhardwaj M, Tabassum H, Raisuddin S, Parvez S (2015) Cisplatin hepatotoxicity mediated by mitochondrial stress. Drug Chem Toxicol 13:1–8Google Scholar
  19. 19.
    Mohan S, Smyth BJ, Namin A, Phillips G, Gratton MA (2014) Targeted amelioration of cisplatin-induced ototoxicity in guinea pigs. Otolaryngol Head Neck Surg 151:836–839CrossRefPubMedGoogle Scholar
  20. 20.
    Hassan I, Chibber S, Khan AA, Naseem I (2013) Cisplatin-induced neurotoxicity in vivo can be alleviated by riboflavin under photoillumination. Cancer Biother Radiopharm 28:160–168CrossRefPubMedGoogle Scholar
  21. 21.
    Yüce A, Atssahin A, Çeribasi AO, Aksakal M (2005) Ellagic acid prevents cisplatin-induced oxidative stress in liver and heart tissue of rats. Basic Clin Pharmacol Toxicol 101:345–359CrossRefGoogle Scholar
  22. 22.
    Tuan BT, Visacri MB, Amaral LS et al (2016) Effects of high-dose cisplatin chemotherapy and conventional radiotherapy on urinary oxidative and nitrosative stress biomarkers in patients with head and neck cancer. Basic Clin Pharmacol Toxicol 118:83–86CrossRefPubMedGoogle Scholar
  23. 23.
    Fuchs-Tarlovsky V, Rivera MAC, Altamirano KA, Lopez-Alvarenga JC, Ceballo-Reyes GM (2013) Antioxidant supplementation has a positive effect on oxidative stress and hematological toxicity during oncology treatment in cervical cancer patients. Support Care Cancer 21:1359–1363CrossRefPubMedGoogle Scholar
  24. 24.
    Yao X, Panichpisal K, Kurtzman N, Nugent K (2007) Cisplatin nephrotoxicity: a review. Am J Med Sci 334:115–124CrossRefPubMedGoogle Scholar
  25. 25.
    Santos NA, Bezerra CS, Martins NM, Curti C, Bianchi ML, Santos AC (2008) Hydroxyl radical scavenger ameliorates cisplatin-induced nephrotoxicity by preventing oxidative stress, redox state unbalance, impairment of energetic metabolism and apoptosis in rat kidney mitochondria. Cancer Chemother Pharmacol 61:145–155CrossRefPubMedGoogle Scholar
  26. 26.
    Atessahín A, Çeribassi AO, Yuce A, Bulmus O, Çikim G (2006) Role of ellagic acid against cisplatin-induced nephrotoxicity and oxidative stress in rats. Basic Clin Pharmacol Toxicol 100:121–126Google Scholar
  27. 27.
    Ahmad S (2010) Platinum-DNA interactions and subsequent cellular processes controlling sensitivity to anticancer platinum complexes. Chem Biodivers 7:543–566CrossRefPubMedGoogle Scholar
  28. 28.
    Sestakova Z, Kalavska K, Hurbanova L et al (2016) The prognostic value of DNA damage level in peripheral blood lymphocytes of chemotherapy-naïve patients with germ cell cancer. Oncotarget 46:75996–76005Google Scholar
  29. 29.
    Arany I, Safirstein RL (2003) Cisplatin nephrotoxicity. Semin Nephrol 23:460–464CrossRefPubMedGoogle Scholar
  30. 30.
    Go R, Adjel A (1999) Review of the comparative pharmacology and clinical activity of cisplatin and carboplatin. J Clin Oncol 17:409–422CrossRefPubMedGoogle Scholar
  31. 31.
    Davis CA, Nick HS, Agarwal A (2001) Manganese superoxide dismutase attenuates cisplatin-induced renal injury: importance of superoxide. J Am Soc Nephrol 12:2683–2690PubMedGoogle Scholar
  32. 32.
    Nishikawa M, Nagatomi H, Chang BJ, Sato E, Inoue M (2001) Targeting superoxide dismutase to renal proximal tubule cells inhibits mitochondrial injury and renal dysfunction induced by cisplatin. Arch Biochem Biophys 387:78–84CrossRefPubMedGoogle Scholar
  33. 33.
    Tsutsumishita Y, Onda T, Okada K et al (1998) Involvement of H2O2 production in cisplatin-induced nephrotoxicity. Biochem Biophys Res 242:310–312CrossRefGoogle Scholar
  34. 34.
    Groeger G, Quiney C, Cotter TG (2009) Hydrogen peroxide as a cell-survival signaling molecule. Antioxid Redox Signal 11:2655–2671CrossRefPubMedGoogle Scholar
  35. 35.
    Lambeth JD (2004) NOX enzymes and the biology of reactive oxygen. Nat Rev Immunol 4:181–189CrossRefPubMedGoogle Scholar
  36. 36.
    Aitken RJ, Bakes MA, O’Brian M (2004) Shedding light on chemiluminescence: the application of chemiluminescence in diagnostic andrology. J Androl 25:455–465CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  • Júlia C. F. Quintanilha
    • 1
  • Marília B. Visacri
    • 1
  • Vanessa M. Sousa
    • 2
  • Larissa B. Bastos
    • 2
  • Camila O. Vaz
    • 2
  • João P. O. Guarnieri
    • 2
  • Laís S. Amaral
    • 1
  • Carina Malaguti
    • 1
  • Carmen S. P. Lima
    • 1
  • Anibal E. Vercesi
    • 1
  • Patricia Moriel
    • 2
  1. 1.School of Medical SciencesUniversity of Campinas (UNICAMP)CampinasBrazil
  2. 2.Faculty of Pharmaceutical SciencesUniversity of Campinas (UNICAMP)CampinasBrazil

Personalised recommendations