Saad Karim M, Elmasry Khaled, Baban Babak, Livingston Man J, Dong Zheng, Abdelmageed Marwa E, Abdelaziz Rania R, Suddek Ghada M, Elmarakby Ahmed A
Department of Oral Biology and Diagnostic Sciences, The Dental College of Georgia, Augusta University, 1450 Laney Walker Blvd, Augusta, GA 30912, USA.
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt.
Int J Mol Sci. 2025 Apr 26;26(9):4115. doi: 10.3390/ijms26094115.
Cisplatin is a highly cytotoxic drug used for the treatment of head, neck, and soft tissue cancers; however, it has nephrotoxic effects that can lead to acute kidney injury. Protocatechuic acid (PCA) is a natural widely available antioxidant found in many fruits such as kiwi, mango, and berries. We have recently shown that PCA reduced renal injury in a mouse model of unilateral ureteral obstruction. The current study aims to investigate the protective effects of PCA in Cisplatin-induced inflammation in vitro in Boston University Mouse Proximal Tubular (BUMPT) cells. BUMPT cells were cultured in complete DMEM. Confluent BUMPT cells were then treated with 20 μM Cisplatin ± PCA 50 or 100 μM for 24 h. PCA treatment showed a dose-depending increase in % cell viability in Cisplatin-treated BUMPT cells. PCA treatment also dose-dependently decreased Cisplatin-induced increases in oxidative stress (ROS and TBARS), inflammation (p-NF-κB and IL-6), and apoptosis (cleaved caspase-3 and % of TUNEL cells) compared to Cisplatin-only treatment. The reduction in oxidative stress, inflammation, and apoptosis with PCA treatment in Cisplatin-treated BUMPT cells was associated with decreases in tubular physical barrier resistance and the expression of the tight junction protein zonula occludens-1 (ZO-1) when compared to BUMPT cells treated with Cisplatin alone. The current findings suggest that PCA treatment improves tubular barrier function in Cisplatin-treated BUMPT cells via reductions in oxidative stress, inflammation, and apoptosis.
顺铂是一种用于治疗头颈部和软组织癌症的高细胞毒性药物；然而，它具有肾毒性作用，可导致急性肾损伤。原儿茶酸（PCA）是一种天然且广泛存在的抗氧化剂，存在于许多水果中，如猕猴桃、芒果和浆果。我们最近发现，PCA可减轻单侧输尿管梗阻小鼠模型中的肾损伤。本研究旨在探讨PCA对波士顿大学小鼠近端肾小管（BUMPT）细胞中顺铂诱导的体外炎症的保护作用。BUMPT细胞在完全的DMEM培养基中培养。然后，将汇合的BUMPT细胞用20μM顺铂±50或100μM PCA处理24小时。PCA处理显示，在顺铂处理的BUMPT细胞中，细胞活力百分比呈剂量依赖性增加。与仅用顺铂处理相比，PCA处理还剂量依赖性地降低了顺铂诱导的氧化应激（ROS和TBARS）、炎症（p-NF-κB和IL-6）以及细胞凋亡（裂解的半胱天冬酶-3和TUNEL细胞百分比）的增加。与单独用顺铂处理的BUMPT细胞相比，PCA处理顺铂处理的BUMPT细胞时，氧化应激、炎症和细胞凋亡的减少与肾小管物理屏障阻力的降低以及紧密连接蛋白闭合蛋白-1（ZO-1）表达的降低有关。目前的研究结果表明，PCA处理通过降低氧化应激、炎症和细胞凋亡来改善顺铂处理的BUMPT细胞中的肾小管屏障功能。
