肝毒性和肾毒性是接受 5-氟尿嘧啶 (5-FU)（一种嘧啶类似物抗代谢抗癌药物）治疗的癌症患者引起的严重不良反应。本研究的目的是评估 PPAR α/γ 激动剂（Saroglitazar；SARO）对 5-FU 诱导的大鼠肝肾损伤的影响。雄性大鼠被随机分为四组：对照组、5-FU、5-FU SARO（2 毫克/千克）和 5-FU SARO（4 毫克/千克）。大鼠每周一次腹腔注射 75 mg/kg 5-FU，持续三周。通过口腔注射器连续三周口服 Saroglitazar（2 和 4 mg/kg/天）。第22天，对大鼠实施安乐死，并对它们的肝脏和肾脏进行形态学、生化、组织学和免疫组织化学分析。沙格列扎治疗显着降低血清肝和肾功能生物标志物。此外，它还成功调节肝脏和肾脏的炎症介质和标志物（NF-κB P65、TNF-α、cleaved caspase-1、IL-1β 和 p-p38 MAPK）以及氧化应激相关参数（MDA、GSH、 SOD、Keap1、Nrf-2 和 HO-1) 呈剂量依赖性。此外，SARO 可以减弱 5-FU 诱导的裂解 caspase-3 的激活，并改善肝脏和肾脏组织的组织病理学检查。 Saroglitazar 可能是 5-FU 毒性的可行治疗选择，因为它阻止了 NF-的相互作用网络kB 和 Nrf2 信号通路与细胞凋亡。版权所有 © 2024 Elsevier B.V. 保留所有权利。

Hepatotoxicity and nephrotoxicity are significant adverse effects caused in cancer patients treated with 5-Flurouracil (5-FU), a pyrimidine analogue anti-metabolite anticancer drug. The purpose of this research was to evaluate the impact of PPAR α/γ agonist (Saroglitazar; SARO) on 5-FU-induced hepatorenal damage in rats.Male rats were randomly assigned to four groups: control, 5-FU, 5-FU + SARO (2 mg/kg), and 5-FU + SARO (4 mg/kg). Rats received 75 mg/kg 5-FU intraperitoneally once weekly for three weeks. Saroglitazar (2 and 4 mg/kg/day) was orally supplied by oral syringe for three consecutive weeks. On day 22, rats were euthanized and their livers and kidneys were subjected to morphological, biochemical, histological, and immunohistochemical analysis.Saroglitazar treatment significantly decreased serum liver and kidney function biomarkers. In addition, it successfully modulated liver and kidney levels of inflammatory mediators and markers (NF-κB P65, TNF-α, cleaved caspase-1, IL-1β and p-p38 MAPK) and oxidative stress-related parameters (MDA, GSH, SOD, Keap1, Nrf-2 and HO-1) in a dose dependent manner. Furthermore, SARO could attenuate 5-FU-induced activation of cleaved caspase-3 as well as improved histopathological examination of both liver and kidney tissues.Saroglitazar may be a viable therapy option for 5-FU toxicity as it halts the interaction network of NF-kB and Nrf2 signaling pathways and apoptosis.Copyright © 2024 Elsevier B.V. All rights reserved.