Cisplatin is an anticancer drug commonly used for solid tumors. However, it causes nephrotoxicity. OAT1 and OAT3 are organic anion transporters known to contribute to the uptake of cisplatin into renal tubular cells. The present study was designed to examine the protective role of ellagic acid nanoformulation (ellagic acid nano) on cisplatin-induced nephrotoxicity in rats, and the role of OAT1/OAT3 in this effect. Four groups of male Wistar rats were used (n = 6): (1) control, (2) cisplatin (7.5 mg/kg single dose, intraperitoneal), (3) cisplatin + ellagic acid nano (1 mg/kg), and (4) cisplatin + ellagic acid nano (2 mg/kg). Nephrotoxic rats treated with ellagic acid nano exhibited a significant reduction in elevated serum creatinine, urea, and oxidative stress marker, malondialdehyde (MDA). Additionally, ellagic acid nano restored renal glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx). Ellagic acid nano improved the histopathological changes induced by cisplatin, such as tubular dilatation, necrosis, and degeneration. Interestingly, OAT1 and OAT3 showed significantly lower expression at both mRNA and protein levels following ellagic acid nano treatment relative to the cisplatin-exposed group. These findings reveal a potential inhibitory role of ellagic acid antioxidant on OAT1 and OAT3 expression and thus explains its nephroprotective effect against cisplatin nephrotoxicity.

中文翻译：

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纳米鞣花酸抵消顺铂诱导的 OAT1 和 OAT3 上调：一种可能的肾保护机制

顺铂是一种常用于治疗实体瘤的抗癌药物。然而，它会引起肾毒性。OAT1 和 OAT3 是有机阴离子转运蛋白，已知有助于肾小管细胞摄取顺铂。本研究旨在探讨鞣花酸纳米制剂（鞣花酸纳米）对顺铂诱导的大鼠肾毒性的保护作用，以及OAT1/OAT3在该作用中的作用。使用四组雄性 Wistar 大鼠（n = 6）：（1）对照，（2）顺铂（7.5 mg/kg 单剂量，腹腔注射），（3）顺铂 + 鞣花酸纳米（1 mg/kg），和(4)顺铂+纳米鞣花酸(2mg/kg)。用纳米鞣花酸治疗的肾毒性大鼠表现出血清肌酐、尿素和氧化应激标志物丙二醛（MDA）升高的显着降低。此外，鞣花酸纳米还可以恢复肾谷胱甘肽 (GSH)、超氧化物歧化酶 (SOD)、过氧化氢酶 (CAT) 和谷胱甘肽过氧化物酶 (GPx)。纳米鞣花酸可改善顺铂引起的肾小管扩张、坏死、变性等组织病理学变化。有趣的是，与顺铂暴露组相比，鞣花酸纳米处理后 OAT1 和 OAT3 的 mRNA 和蛋白质水平表达均显着降低。这些发现揭示了鞣花酸抗氧化剂对 OAT1 和 OAT3 表达的潜在抑制作用，从而解释了其对顺铂肾毒性的肾保护作用。