顺铂肾毒性是众所周知的由氧化应激和炎症引起的紧急临床病症。柚皮苷(NAR)被认为是一种具有肾脏保护作用的抗氧化剂,能够去除活性氧。据报道,脂肪组织来源的间充质干细胞(AD-MSC)具有抗炎和抗氧化特性。本研究通过SIRT-1/Nrf-2/HO-1途径检查了NAR和AD-MSC的组合对顺铂诱导的肾毒性的肾脏保护作用,而不是单独使用它们。本研究包括五组(每组8只)雄性Sprague-Dawley大鼠(200-220g):假,顺铂:接受顺铂的大鼠(6.5mg/kg,i.p.)在第4天;NAR顺铂:用NAR预处理的大鼠(1周,第4天i.p.)+顺铂;AD-MSCs:第5天尾静脉注射AD-MSCs(1×106)+第4天顺铂;NAR+AD-MSCs+顺铂。第8天,将动物麻醉以获得组织和血液样品。生化因素,炎症,氧化应激,和基因表达进行了探索。顺铂增加血尿素氮,肌酐,炎症,和氧化应激。此外,Sirtuin1、核因子-红细胞相关因子2(Nrf-2)mRNA表达,血红素加氧酶-1(HO-1)显著降低。此外,顺铂导致肾脏结构紊乱(肾小球萎缩,细胞浸润,和肾小管功能障碍),如组织学发现所证实。然而,NAR预处理,AD-MSC管理,或两者的组合显著逆转了这些变化。总的来说,当一起使用时,NAR和AD-MSCs通过抑制炎症对顺铂诱导的肾功能损害有更强的作用,减少氧化应激,增加Sirtuin1/Nrf-2/HO-1通路。
Cisplatin
nephrotoxicity is a well-known emergency clinical condition caused by oxidative stress and inflammation. Naringin (NAR) is considered an antioxidant agent with renoprotective effects capable of removing reactive oxygen species. Adipose tissue-derived mesenchymal stem cells (AD-MSCs) are reported to have anti-inflammatory and antioxidant properties. The present research examined the renoprotective effect of the combination of NAR and AD-MSCs as opposed to each one alone on cisplatin-induced
nephrotoxicity through SIRT-1/Nrf-2/HO-1 pathway. This study included five groups (n = 8 each) of male Sprague-Dawley rats (200 - 220 g): sham, cisplatin: rats receiving cisplatin (6.5 mg/kg, i.p.) on the 4th day; NAR+cisplatin: rats pretreated with NAR (1 week, i.p.) + cisplatin on the 4th day; AD-MSCs: rats receiving AD-MSCs (1 × 106) by injection through the tail vein on the 5th day + cisplatin on the 4th day; and NAR+AD-MSCs+cisplatin. On the 8th day, the animals were anesthetized to obtain tissue and blood samples. Biochemical factors, inflammation, oxidative stress, and gene expression were explored. Cisplatin increased blood urea nitrogen, creatinine, inflammation, and oxidative stress. Moreover, mRNA expression of Sirtuin1, nuclear factor erythroid 2-related factor 2 (Nrf-2), and heme oxygenase-1 (HO-1) remarkably reduced. Furthermore, cisplatin led to a disturbance in kidney structure (glomerular atrophy, cell infiltrations, and tubular dysfunction) as confirmed by histology findings. However, NAR pretreatment, AD-MSC administration, or a combination of both significantly reversed these changes. Overall, when used together, NAR and AD-MSCs had stronger cisplatin-induced effects on kidney dysfunction by inhibiting inflammation, reducing oxidative stress, and increasing the Sirtuin1/Nrf-2/HO-1 pathway.