Experimental Study of EGCG on Endoplasmic Reticulum Stress-Induced Renal Apoptosis in T2DM Rats

Abstract

Background: Diabetic nephropathy (DN), a severe complication of diabetes, is one of the primary causes of chronic kidney disease (CKD) in China. Epigallocatechin gallate (EGCG), a natural compound found in tea leaves, exhibits both preventive and therapeutic properties against several diseases, including cancer, obesity, diabetes, and cardiovascular diseases. Therefore, this study aimed to investigate the protective effects of EGCG on renal tissue apoptosis induced by endoplasmic reticulum stress in rats with type 2 diabetes mellitus (T2DM). Methods: The kidney tissues of Wistar rats were collected and analyzed following treatment with Streptozotocin (STZ) and EGCG. Moreover, fasting blood glucose (FBG), fasting insulin (FINS), urea nitrogen (UREA), and creatinine (CREA) were assessed using corresponding enzyme-linked immunosorbent assay (ELISA) kits. Similarly, the apoptosis index (AI) was examined utilizing terminal deoxynucleotidyl transferase-mediated dUTP Nick end labeling (TUNEL). Furthermore, the expression levels of C/EBP homologous protein (CHOP) and phosphorylated c-Jun N-terminal kinase (p-JNK) were determined in each group of rats by immunohistochemistry and Western blot analysis. Additionally, the mRNA transcription levels of CHOP and JNK were assessed using real-time fluorescent quantitative polymerase chain reaction (RT-qPCR). Results: Compared to the normal control group (NOR), the levels of FBG, FINS, UREA, CREA, and apoptosis index (AI) were elevated (p < 0.0001) in the diabetic model control group (MOR). Furthermore, the mean optical density values of CHOP and p-JNK, the mRNA and protein expression levels of CHOP, the protein expression levels of p-JNK, and the mRNA expression levels of JNK were significantly increased in the experimental group (p < 0.0001). Additionally, compared to the MOR group, the levels of FBG, FINS, UREA, CREA, and AI were significantly alleviated in both the EGCG low-dose group (EGCG1) and EGCG high-dose group (EGCG2) (p < 0.0001). Similarly, the average optical density values of CHOP and p-JNK, the mRNA and protein expression levels of CHOP, the protein expression level of p-JNK, and the mRNA expression level of JNK were significantly decreased (p < 0.01). Conclusions: These findings indicate that EGCG reduces renal injury and cell apoptosis in diabetic rats by inhibiting the expression of endoplasmic reticulum stress-related proteins, such as CHOP and JNK.