Quintanilha Júlia Coelho França, de Sousa Vanessa Marcilio, Visacri Marília Berlofa, Amaral Laís Sampaio, Santos Roseane Maria Maia, Zambrano Tomás, Salazar Luis Antonio, Moriel Patricia
School of Medical Sciences, University of Campinas (UNICAMP), Campinas, SP, Brazil.
Faculty of Pharmaceutical Sciences, University of Campinas (UNICAMP), 200 Cândido Portinari, Campinas, 13083-871, SP, Brazil.
Cancer Chemother Pharmacol. 2017 Aug;80(2):223-233. doi: 10.1007/s00280-017-3358-x. Epub 2017 Jun 13.
The aim of this study is to evaluate the relationship between the CYP450 enzyme family and cisplatin toxicity.
This article examined a collection of studies suggesting that CYP450 enzymes may influence cisplatin toxicity. We performed a narrative mini-review.
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.
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.
本研究旨在评估细胞色素P450（CYP450）酶家族与顺铂毒性之间的关系。
本文审视了一系列表明CYP450酶可能影响顺铂毒性的研究。我们进行了一项叙述性小型综述。
研究综述表明，CYP450酶在药物性肝毒性和肾毒性中起重要作用，主要是CYP2E1和CYP4A11。研究还表明，顺铂与CYP2E1的相互作用导致活性氧（ROS）和其他氧化剂的生成，从而导致肾损伤；并且顺铂使用和CYP2E1产生的ROS都会增加组织损伤、诱导细胞凋亡并导致肝衰竭。
我们观察到CYP450与顺铂之间存在重要关系，涉及毒性增加。然而，CYP450酶参与顺铂诱导的肾毒性和肝毒性的可能机制需要进一步研究证实。因此，有必要针对CYP450酶介导的顺铂毒性进行更深入的研究，这无疑将有助于更好地理解迄今所涉及的机制。
