Liu Yue, Zhang Ruichen, Velkov Tony, Shen Jianzhong, Tang Shusheng, Dai Chongshan
National Key Laboratory of Veterinary Public Health and Safety, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China.
Technology Innovation Center for Food Safety Surveillance and Detection (Hainan), Sanya Institute of China Agricultural University, Sanya 572025, China.
Antioxidants (Basel). 2025 May 15;14(5):593. doi: 10.3390/antiox14050593.
This study investigated the protective effects of corynoxeine, a natural alkaline compound, on colistin-caused nephrotoxicity using a murine model. Forty mice were divided randomly into control, corynoxeine-only (20 mg/kg/day, intraperitoneal injection), colistin-only (20 mg/kg/day, intraperitoneal injection), and colistin (20 mg/kg/day) + corynoxeine (5 and 20 mg/kg/day) groups (8 mice in each group). All treatments were maintained for seven consecutive days. Results showed that colistin treatment at 20 mg/kg/day for seven days significantly increased serum urea nitrogen and creatinine levels and induced the loss and degeneration of renal tubular epithelial cells, which were markedly ameliorated by corynoxeine co-treatment at 5 or 20 mg/kg/day. Corynoxeine supplementation also markedly attenuated colistin-induced increases in malondialdehyde levels and decreases in reduced glutathione levels and superoxide dismutase and catalase activities in the kidneys. Furthermore, corynoxeine supplementation significantly decreased the expression of transforming growth factor β (TGF-β) and nicotinamide adenine dinucleotide phosphate hydrogen oxidase 4 (NOX4) proteins and nuclear factor kappa B (), interleukin-1beta (), , and tumor necrosis factor-α mRNAs, while it significantly increased the expression of erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) proteins in the kidneys. In conclusion, these results reveal that corynoxeine can protect against colistin-induced nephrotoxicity in mice by inhibiting oxidative stress and inflammation, which may partly be attributed to its ability on the activation of the Nrf2/HO-1 pathway and the inhibition of the TGF-β/NOX4 and NF-κB pathways.
本研究使用小鼠模型，研究了天然碱性化合物巴戟天碱对多粘菌素所致肾毒性的保护作用。将40只小鼠随机分为对照组、单纯巴戟天碱组（20毫克/千克/天，腹腔注射）、单纯多粘菌素组（20毫克/千克/天，腹腔注射）以及多粘菌素（20毫克/千克/天）+巴戟天碱（5毫克/千克/天和20毫克/千克/天）组（每组8只小鼠）。所有处理均连续维持7天。结果显示，20毫克/千克/天的多粘菌素处理7天显著提高了血清尿素氮和肌酐水平，并诱导肾小管上皮细胞丢失和变性，而5毫克/千克/天或20毫克/千克/天的巴戟天碱联合处理可明显改善这些情况。补充巴戟天碱还显著减轻了多粘菌素诱导的肾脏丙二醛水平升高以及还原型谷胱甘肽水平、超氧化物歧化酶和过氧化氢酶活性降低。此外，补充巴戟天碱显著降低了肾脏中转化生长因子β（TGF-β）和烟酰胺腺嘌呤二核苷酸磷酸氧化酶4（NOX4）蛋白以及核因子κB、白细胞介素-1β、[此处原文缺失部分内容]和肿瘤坏死因子-α mRNA的表达，同时显著增加了肾脏中红细胞2相关因子2（Nrf2）和血红素加氧酶-1（HO-1）蛋白的表达。总之，这些结果表明，巴戟天碱可通过抑制氧化应激和炎症来保护小鼠免受多粘菌素诱导的肾毒性，这可能部分归因于其激活Nrf2/HO-1途径以及抑制TGF-β/NOX4和NF-κB途径的能力。
