Graduate School of Medicine, Korea University, Seoul, 136-705, Republic of Korea.
New Drug Development Center, Daegu-Gyeongbuk Medical Innovation Foundation (DGMIF), Daegu, 41061, Republic of Korea.
Sci Rep. 2022 Apr 27;12(1):6837. doi: 10.1038/s41598-022-11011-3.
Thioacetamide (TAA) was administered orally at 0, 10, and 30 mg/kg body weight (BW) daily to Sprague-Dawley rats aged 6-7 weeks for 28 consecutive days. Nephrotoxicity and proteomics were evaluated in the kidneys of rats exposed to TAA. The BW decreased, however, the relative kidneys weight increased. No significant histopathologic abnormalities were found in the kidneys. The numbers of monocytes and platelets were significantly increased. However, the mean corpuscular volume and hematocrit values were decreased significantly in rats exposed to 30 mg/kg BW TAA. The expression levels of Kim-1 and NGAL were increased 4 to 5-fold in the kidneys, resulting in significant nephrotoxicity. Proteomic analysis was conducted and a total of 5221 proteins spots were resolved. Of these, 3 and 21 protein spots were up- and downregulated, respectively. The validation of seven proteins was performed by Western blot analysis. The expression level of ASAP2 was significantly upregulated, whereas RGS14, MAP7Dl, IL-3Rα, Tmod1, NQO2, and MUP were reduced. Sixteen isoforms of MUP were found by the 2DE immunoblot assay and were significantly downregulated with increasing exposure to TAA. MUP isoforms were compared in the liver, kidneys, and urine of untreated rats and a total of 43 isoforms were found.
硫代乙酰胺（TAA）以 0、10 和 30mg/kg 体重（BW）的剂量每天经口给予 6-7 周龄 Sprague-Dawley 大鼠，连续 28 天。在 TAA 暴露的大鼠肾脏中评估了肾毒性和蛋白质组学。BW 降低，而相对肾脏重量增加。在肾脏中未发现明显的组织病理学异常。单核细胞和血小板数量显著增加。然而，暴露于 30mg/kg BW TAA 的大鼠的平均红细胞体积和红细胞压积值显著降低。Kim-1 和 NGAL 的表达水平在肾脏中增加了 4 到 5 倍，导致明显的肾毒性。进行了蛋白质组学分析，共解析了 5221 个蛋白质斑点。其中，3 个和 21 个蛋白质斑点分别上调和下调。通过 Western blot 分析验证了 7 种蛋白质。ASAP2 的表达水平显著上调，而 RGS14、MAP7Dl、IL-3Rα、Tmod1、NQO2 和 MUP 则减少。通过 2DE 免疫印迹检测到 MUP 的 16 种同工型，随着 TAA 暴露的增加，其表达水平显著下调。比较了未处理大鼠肝脏、肾脏和尿液中 MUP 的同工型，共发现 43 种同工型。
