Júlia Coelho França Quintanilha1, Vanessa Marcilio de Sousa2, Marília Berlofa Visacri1, Laís Sampaio Amaral1, Roseane Maria Maia Santos3, Tomás Zambrano4, Luis Antonio Salazar4, Patricia Moriel5,6. 1. School of Medical Sciences, University of Campinas (UNICAMP), Campinas, SP, Brazil. 2. Faculty of Pharmaceutical Sciences, University of Campinas (UNICAMP), 200 Cândido Portinari, Campinas, 13083-871, SP, Brazil. 3. School of Pharmacy, South University, Savannah, GA, USA. 4. Center of Molecular Biology and Pharmacogenetics, Faculty of Medicine, University of La Frontera, Temuco, Chile. 5. School of Medical Sciences, University of Campinas (UNICAMP), Campinas, SP, Brazil. patricia.moriel@fcf.unicamp.br. 6. Faculty of Pharmaceutical Sciences, University of Campinas (UNICAMP), 200 Cândido Portinari, Campinas, 13083-871, SP, Brazil. patricia.moriel@fcf.unicamp.br.
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.
PURPOSE: The aim of this study is to evaluate the relationship between the CYP450 enzyme family and cisplatintoxicity. METHODS: This article examined a collection of studies suggesting that CYP450 enzymes may influence cisplatintoxicity. 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 cisplatintoxicity mediated by CYP450 enzymes, which would undoubtedly contribute to a better understanding of the mechanisms that have been implicated so far.