Department of Biotechnology, Daegu University, Gyeongsan, Gyeongbuk 38453, Korea.
Department of Biotechnology, Daegu University, Gyeongsan, Gyeongbuk 38453, Korea; Stephenson Cancer Center, University of Oklahoma Health Science Center, Oklahoma City, OK 74117, USA.
J Nutr Biochem. 2022 Dec;110:109134. doi: 10.1016/j.jnutbio.2022.109134. Epub 2022 Aug 24.
Rhabdomyolysis induced acute kidney injury (RIAKI) is a life-threatening condition responsible for approximately 19-58% of AKI cases worldwide. We performed an intramuscular injection of glycerol (10 mL/kg) in male wistar rats to induce AKI. Epigallocatechin gallate (EGCG) was administered for 3 consecutive days to evaluate its protective effects. We observed significant downregulation in serum creatinine, blood urea nitrogen (BUN) and LDH at different time points on EGCG treatment groups in a dose-dependent manner. Similarly, H&E staining also revealed that EGCG was able to reduce the formation of damaged tubules and tubular necrosis which was prominently spread throughout the kidney tissue of glycerol treatment group. Concomitantly, we observed upregulated inflammation, ER stress and elevated oxidative stress in the glycerol treated group only, which was significantly normalized upon EGCG treatment in both in vitro and in vivo studies. The occurrence of apoptosis in kidney tubules was found to be relatively higher in glycerol treated group and HO treated HEK-293 cells. The results obtained after EGCG treatment revealed a significant decrease in apoptotic cell population, which was further validated by immunofluorescence staining against p53 and comet assay in HEK-293 cells and p53 IHC in kidney tissues. Western blotting also revealed a systemic downregulation of intrinsic mitochondrial apoptotic pathway markers such as bax, bcl-2, pro and cleaved caspase 3, caspase 9 and PARP1. Additionally, the results for flow cytometry analysis and TUNEL assay corroborated apoptotic equilibrium. Conclusively, we reckon EGCG as a multi-therapeutic natural product that can be used the for treatment of AKI.
横纹肌溶解症引起的急性肾损伤（RIAKI）是一种危及生命的病症，约占全球 AKI 病例的 19-58%。我们对雄性 Wistar 大鼠进行肌内注射甘油（10 mL/kg）以诱导 AKI。连续 3 天给予表没食子儿茶素没食子酸酯（EGCG），以评估其保护作用。我们观察到 EGCG 治疗组在不同时间点的血清肌酐、血尿素氮（BUN）和 LDH 显著下调，呈剂量依赖性。同样，H&E 染色也表明，EGCG 能够减少受损肾小管的形成和肾小管坏死，这种坏死在甘油处理组的整个肾脏组织中广泛存在。同时，我们观察到只有在甘油处理组中才会出现炎症、内质网应激和氧化应激的上调，而在体外和体内研究中，EGCG 处理均能显著使其正常化。在甘油处理组中，发现肾小管细胞凋亡的发生率相对较高，而在 HO 处理的 HEK-293 细胞中则没有。EGCG 处理后的结果显示，凋亡细胞群体显著减少，这在 HEK-293 细胞中的 p53 免疫荧光染色和彗星试验以及肾脏组织中的 p53 IHC 中得到了进一步验证。Western blot 还显示，内在线粒体凋亡途径标志物如 bax、bcl-2、pro 和 cleaved caspase 3、caspase 9 和 PARP1 的系统下调。此外，流式细胞术分析和 TUNEL 试验的结果也证实了凋亡平衡。综上所述，我们认为 EGCG 是一种多治疗天然产物，可用于治疗 AKI。
