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Involvement of cytochrome P450 in cisplatin treatment: implications for toxicity

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Abstract

Purpose

The aim of this study is to evaluate the relationship between the CYP450 enzyme family and cisplatin toxicity.

Methods

This article examined a collection of studies suggesting that CYP450 enzymes may influence cisplatin toxicity. We performed a narrative mini-review.

Results

The studies review showed that CYP450 enzymes have an important role in drug-induced hepatotoxicity and nephrotoxicity, mainly CYP2E1 and CYP4A11. The studies also suggested that the cisplatin and CYP2E1 interaction leads to the generation of reactive oxygen species (ROS) and other oxidants resulting in renal injury; and that ROS generated by both the use of cisplatin and by the CYP2E1 increases tissue damage, induces apoptosis, and causes liver failure.

Conclusions

We observed that there is an important relationship between CYP450 and cisplatin, involving increased toxicity. However, the possible mechanisms described for the involvement of CYP450 enzymes in nephrotoxicity and hepatotoxicity induced by cisplatin need to be confirmed by further studies. Therefore, there is a need for a deeper investigation focusing on cisplatin toxicity mediated by CYP450 enzymes, which would undoubtedly contribute to a better understanding of the mechanisms that have been implicated so far.

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Acknowledgements

We are thankful to the São Paulo Research Foundation (FAPESP) for the financial support.

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Author notes

  1. Júlia Coelho França Quintanilha and Vanessa Marcilio de Sousa contributed equally to this work.

Authors and Affiliations

  1. School of Medical Sciences, University of Campinas (UNICAMP), Campinas, SP, Brazil

    Júlia Coelho França Quintanilha, Marília Berlofa Visacri, Laís Sampaio Amaral & Patricia Moriel

  2. Faculty of Pharmaceutical Sciences, University of Campinas (UNICAMP), 200 Cândido Portinari, Campinas, 13083-871, SP, Brazil

    Vanessa Marcilio de Sousa & Patricia Moriel

  3. School of Pharmacy, South University, Savannah, GA, USA

    Roseane Maria Maia Santos

  4. Center of Molecular Biology and Pharmacogenetics, Faculty of Medicine, University of La Frontera, Temuco, Chile

    Tomás Zambrano & Luis Antonio Salazar

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  1. Júlia Coelho França Quintanilha
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  2. Vanessa Marcilio de Sousa
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Correspondence to Patricia Moriel.

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Author JCFQ declares that she has no conflict of interest. Author VMS declares that she has no conflict of interest. Author MBV declares that she has no conflict of interest. Author LSA declares that she has no conflict of interest. Author RMMS declares that she has no conflict of interest. Author TZ declares that he has no conflict of interest. Author LAS declares that he has no conflict of interest. Author PM declares that she has no conflict of interest.

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Quintanilha, J.C.F., de Sousa, V.M., Visacri, M.B. et al. Involvement of cytochrome P450 in cisplatin treatment: implications for toxicity. Cancer Chemother Pharmacol 80, 223–233 (2017). https://doi.org/10.1007/s00280-017-3358-x

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  • DOI: https://doi.org/10.1007/s00280-017-3358-x

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