Kidney Transplantation, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an City, China.
Department of Nephropathy, Shijiazhuang Pingan Hospital, Shijiazhuang City, China.
J Biochem Mol Toxicol. 2022 Apr;36(4):e22988. doi: 10.1002/jbt.22988. Epub 2022 Feb 21.
The present research work was proposed to discover the beneficial roles of ponicidin against the streptozotocin (STZ)-induced diabetic nephropathy (DN) in rats via modulating the oxidative stress and inflammation. The DN was initiated to the Wistar rats via administering 45 mg/kg of STZ and then diabetic animals were supplemented with 50 mg/kg of ponicidin and 150 mg/kg of metformin (standard drug) for 8 weeks. The body weight and food intake of animals were checked every week. The glucose, insulin, and homeostasis model assessment- insulin resistance (HOMA-IR) levels in the serum were assessed using kits. The levels of reactive oxygen species (ROS) accumulation, oxidative stress and antioxidant markers, and pro-inflammatory cytokines were examined using assay kits. The levels of lipid profiles and renal function markers were investigated using respective kits. The renal tissues were analyzed microscopically to detect the histological alterations. The ponicidin treatment effectively decreased the body weight, food intake, HOMA-IR, and HbAlc levels in the DN animals. The levels of ROS and MDA were decreased and superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and glutathione reductase (GR) activities were improved by the ponicidin. The ponicidin also reduced the blood urea nitrogen (BUN), creatinine, lactate dehydrogenase (LDH), and kidney injury molecule (KIM-1) levels. The levels of low-density lipoprotein (LDL), very-low-density lipoprotein (VLDL), free fatty acid (FFA), and total cholesterol (TC) were decreased and the high-density lipoprotein (HDL) level was improved by the ponicidin treatment to the DN rats. The tumor necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β), nuclear factor-kappa B (NF-κB), and IL-6 levels were appreciably attenuated by the ponicidin. The ponicidin also ameliorated the DM-provoked histological alterations in the renal tissues. In conclusion, this study work evidenced that ponicidin has the therapeutic action in ameliorating the development of DN via averting oxidative stress, inflammation, and renal injury. It could be a promising therapeutic agent to treat DN in the future.
本研究旨在通过调节氧化应激和炎症来发现蓬尼定对链脲佐菌素（STZ）诱导的糖尿病肾病（DN）大鼠的有益作用。通过向 Wistar 大鼠给予 45mg/kg 的 STZ 来引发 DN，然后用 50mg/kg 的蓬尼定和 150mg/kg 的二甲双胍（标准药物）对糖尿病动物进行补充，持续 8 周。每周检查动物的体重和食物摄入量。使用试剂盒测定血清中的葡萄糖、胰岛素和稳态模型评估-胰岛素抵抗（HOMA-IR）水平。使用测定试剂盒测定活性氧（ROS）积累、氧化应激和抗氧化标志物以及促炎细胞因子的水平。使用各自的试剂盒研究脂质谱和肾功能标志物的水平。用显微镜分析肾组织以检测组织学改变。蓬尼定治疗有效降低了 DN 动物的体重、食物摄入量、HOMA-IR 和 HbAlc 水平。ROS 和 MDA 的水平降低，超氧化物歧化酶（SOD）、过氧化氢酶（CAT）、谷胱甘肽过氧化物酶（GPx）和谷胱甘肽还原酶（GR）的活性得到改善。蓬尼定还降低了血尿素氮（BUN）、肌酐、乳酸脱氢酶（LDH）和肾脏损伤分子（KIM-1）的水平。低密度脂蛋白（LDL）、极低密度脂蛋白（VLDL）、游离脂肪酸（FFA）和总胆固醇（TC）的水平降低，高密度脂蛋白（HDL）的水平通过蓬尼定治疗提高了 DN 大鼠。肿瘤坏死因子-α（TNF-α）、白细胞介素-1β（IL-1β）、核因子-κB（NF-κB）和白细胞介素-6（IL-6）的水平显著降低。蓬尼定还改善了 DM 引起的肾组织的组织学改变。总之，这项研究工作表明，蓬尼定通过防止氧化应激、炎症和肾损伤，在改善 DN 的发展方面具有治疗作用。它可能是未来治疗 DN 的一种有前途的治疗剂。
