PDF(Pubmed)
Abstract：
OBJECTIVE: Cisplatin [cis-diamminedichloroplatinum(II), CDDP] is a widely used and effective antitumor drug in clinical settings, notorious for its nephrotoxic side effects. This study investigated the mechanisms of CDDP-induced damage in African green monkey kidney (Vero) cells, with a focus on the role of Peroxiredoxin I (Prx I) and Peroxiredoxin II (Prx II) of the peroxiredoxin (Prx) family, which scavenge reactive oxygen species (ROS).
METHODS: We utilized the Vero cell line derived from African green monkey kidneys and exposed these cells to various concentrations of CDDP. Cell viability, apoptosis, ROS levels, and mitochondrial membrane potential were assessed.
RESULTS: CDDP significantly compromised Vero cell viability by elevating both cellular and mitochondrial ROS, which led to increased apoptosis. Pretreatment with the ROS scavenger N-acetyl-L-cysteine (NAC) effectively reduced CDDP-induced ROS accumulation and subsequent cell apoptosis. Furthermore, CDDP reduced Prx I and Prx II levels in a dose- and time-dependent manner. The inhibition of Prx I and II exacerbated cell death, implicating their role in CDDP-induced accumulation of cellular ROS. Additionally, CDDP enhanced the phosphorylation of MAPKs (p38, ERK, and JNK) without affecting AKT. The inhibition of these pathways significantly attenuated CDDP-induced apoptosis.
CONCLUSIONS: The study highlights the involvement of Prx proteins in CDDP-induced nephrotoxicity and emphasizes the central role of ROS in cell death mediation. These insights offer promising avenues for developing clinical interventions to mitigate the nephrotoxic effects of CDDP.
METHODS: We utilized the Vero cell line derived from African green monkey kidneys and exposed these cells to various concentrations of CDDP. Cell viability, apoptosis, ROS levels, and mitochondrial membrane potential were assessed.
RESULTS: CDDP significantly compromised Vero cell viability by elevating both cellular and mitochondrial ROS, which led to increased apoptosis. Pretreatment with the ROS scavenger N-acetyl-L-cysteine (NAC) effectively reduced CDDP-induced ROS accumulation and subsequent cell apoptosis. Furthermore, CDDP reduced Prx I and Prx II levels in a dose- and time-dependent manner. The inhibition of Prx I and II exacerbated cell death, implicating their role in CDDP-induced accumulation of cellular ROS. Additionally, CDDP enhanced the phosphorylation of MAPKs (p38, ERK, and JNK) without affecting AKT. The inhibition of these pathways significantly attenuated CDDP-induced apoptosis.
CONCLUSIONS: The study highlights the involvement of Prx proteins in CDDP-induced nephrotoxicity and emphasizes the central role of ROS in cell death mediation. These insights offer promising avenues for developing clinical interventions to mitigate the nephrotoxic effects of CDDP.
摘要：
目的：顺铂[顺式-二氨基二氯铂（II），CDDP]是临床上广泛使用和有效的抗肿瘤药物，因其肾毒性副作用而臭名昭著。本研究探讨了CDDP诱导非洲绿猴肾（Vero）细胞损伤的机制。重点关注过氧化物酶（Prx）家族的过氧化物酶I（PrxI）和过氧化物酶II（PrxII）的作用，清除活性氧(ROS)。
方法:我们利用源自非洲绿猴肾的Vero细胞系,并将这些细胞暴露于各种浓度的CDDP。细胞活力，凋亡，ROS水平,和线粒体膜电位进行了评估。
结果：CDDP通过提高细胞和线粒体ROS显著损害Vero细胞的活力，导致细胞凋亡增加。用ROS清除剂N-乙酰-L-半胱氨酸(NAC)预处理有效减少CDDP诱导的ROS积累和随后的细胞凋亡。此外，CDDP以剂量和时间依赖性方式降低PrxI和PrxII水平。抑制PrxI和II会加剧细胞死亡，它们在CDDP诱导的细胞ROS积累中的作用。此外,CDDP增强了MAPK的磷酸化（p38，ERK，和JNK）而不影响AKT。这些途径的抑制显著减弱了CDDP诱导的细胞凋亡。
结论：该研究强调了Prx蛋白参与CDDP诱导的肾毒性，并强调了ROS在细胞死亡介导中的核心作用。这些见解为开发临床干预措施以减轻CDDP的肾毒性作用提供了有希望的途径。
方法:我们利用源自非洲绿猴肾的Vero细胞系,并将这些细胞暴露于各种浓度的CDDP。细胞活力，凋亡，ROS水平,和线粒体膜电位进行了评估。
结果：CDDP通过提高细胞和线粒体ROS显著损害Vero细胞的活力，导致细胞凋亡增加。用ROS清除剂N-乙酰-L-半胱氨酸(NAC)预处理有效减少CDDP诱导的ROS积累和随后的细胞凋亡。此外，CDDP以剂量和时间依赖性方式降低PrxI和PrxII水平。抑制PrxI和II会加剧细胞死亡，它们在CDDP诱导的细胞ROS积累中的作用。此外,CDDP增强了MAPK的磷酸化（p38，ERK，和JNK）而不影响AKT。这些途径的抑制显著减弱了CDDP诱导的细胞凋亡。
结论：该研究强调了Prx蛋白参与CDDP诱导的肾毒性，并强调了ROS在细胞死亡介导中的核心作用。这些见解为开发临床干预措施以减轻CDDP的肾毒性作用提供了有希望的途径。
