Cisplatin-induced nephrotoxicity limits its wide application as a chemotherapeutic drug. Betaine is a natural trimethylglycine compound involved in several biological reactions. In this study, the protective effect of betaine against cisplatin-induced nephrotoxicity through modulating the expression of microRNA 34a (miRNA 34a), p53, apoptosis, and inflammation was investigated. Adult Wistar rats were divided into normal group (received vehicle); betaine group (received 250 mg betaine/kg BW/day via oral gavage from Day 1 to Day 25); cisplatin group (received a single intraperitoneal dose of cisplatin at 5 mg/kg BW on Day 21) and betaine + cisplatin group (received the same doses of betaine and cisplatin). The results demonstrated that the cisplatin group exhibited severe kidney tissue damage and an increase in blood creatinine and urea levels. Furthermore, the cisplatin group showed a significant upregulation of miRNA 34a and higher levels of phospho-p53, caspase 3, cytochrome c, NF_kB, and IL-1β compared to the normal group. Remarkably, the betaine + cisplatin group showed significantly decreased blood creatinine and urea concentrations, decreased levels of miRNA 34a, phospho-p53, caspase 3, cytochrome c, NF_kB, and IL-1β as well as improved kidney tissue integrity compared to the cisplatin group. In conclusion, cisplatin-induced nephrotoxicity in rats was associated with upregulation of miRNA 34a expression, apoptosis, and inflammation in p53-dependent manner. These effects were reversed by betaine administration that ultimately improved the kidney function and tissue integrity.

中文翻译：

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甜菜碱在顺铂诱导的大鼠肾毒性中通过 p53 依赖性方式下调 microRNA 34a 表达

顺铂诱导的肾毒性限制了其作为化疗药物的广泛应用。甜菜碱是一种参与多种生物反应的天然三甲基甘氨酸化合物。在这项研究中，研究了甜菜碱通过调节 microRNA 34a (miRNA 34a)、p53、细胞凋亡和炎症的表达对顺铂诱导的肾毒性的保护作用。成年Wistar大鼠分为正常组（接受载体）；甜菜碱组（从第 1 天到第 25 天通过口服管饲法接受 250 毫克甜菜碱/千克体重/天）；顺铂组（在第 21 天以 5 毫克/千克体重接受单次腹膜内顺铂剂量）和甜菜碱 + 顺铂组（接受相同剂量的甜菜碱和顺铂）。结果表明，顺铂组表现出严重的肾组织损伤和血肌酐和尿素水平升高。_k B 和 IL-1β 与正常组相比。值得注意的是，与对照组相比，甜菜碱 + 顺铂组的血肌酐和尿素浓度显着降低，miRNA 34a、磷酸-p53、半胱天冬酶 3、细胞色素 c、NF _k B 和 IL-1β 的水平降低，肾组织完整性得到改善。顺铂组。总之，顺铂诱导的大鼠肾毒性与 p53 依赖性方式的 miRNA 34a 表达、细胞凋亡和炎症的上调有关。这些影响被甜菜碱给药逆转，最终改善了肾功能和组织完整性。