Epigallocatechin-3-Gallate Attenuates Adriamycin-Induced Focal Segmental Glomerulosclerosis via Suppression of Oxidant Stress and Apoptosis by Targeting Hypoxia-Inducible Factor-1α/ Angiopoietin-Like 4 Pathway

Abstract

Background: Focal and segmental glomerular sclerosis (FSGS) is a common cause of nephrotic syndrome and end-stage renal disease. It has been reported that overproduction of reactive oxygen species (ROS) and cell apoptosis are associated with the development of FSGS. Epigallocatechin-3-gallate (EGCG) is a bioactive constituent accounting for more than 50% of the total catechins in green tea, which have anti-oxidative and anti-apoptotic effects. Based on this, this study was designed to evaluate the renoprotective effect of EGCG treatment on Adriamycin-induced FSGS. ­Methods: In C57BL/6 mice, Adriamycin nephropathy (AN) was induced by Adriamycin (10 mg/kg body weight, diluted in normal saline) via a tail vein on day 0. Then the mice were given with EGCG (20 mg/kg body weight) or YC-1 (Lificiguat, a specific inhibitor of hypoxia-inducible factor-1α [HIF-1α], 50 mg/kg body weight) or both intraperitoneally. Both the EGCG and YC-1 were given on the day of Adriamycin injection and continued for 6 weeks. The animals were organized into the following 5 groups for the animal experiments: the control group, the AN group, the AN + EGCG group, the AN + YC-1 group and the AN + EGCG + YC-1 group. At 6 weeks, the mice were sacrificed; kidneys and blood samples were collected for further analysis. The HIF-1α and the angiopoietin-like 4 (ANGPTL4) expression were detected by Western blot, real-time PCR, immunohistochemistry or immunofluorescence. Dihydroethidium staining and NADPH oxidase 1 (Nox1) measurement were used to detect ROS production. Terminal deoxynucleotide transferase-mediated dUTP nick end-labeling (TUNEL) staining and caspase-3 measurement was used to detect cell apoptosis. Results: When the animals were treated with Adriamycin, both the ROS production and TUNEL positive cells increased. Besides, the expression of HIF-1α, ANGPTL4, and caspase-3 were also up-regulated, while EGCG treatment could attenuate these changes. Interestingly, compared with treatment with YC-1 or EGCG alone, more pronounced inhibition of ANGPTL4, caspase-3 and Nox1 were obtained when YC-1 and EGCG were administered simultaneously. Conclusion: EGCG attenuates FSGS through the suppression of Oxidant Stress and apoptosis by targeting the HIF-1α/ANGPTL4 pathway.

The Inhibitory Effect of (−)-Epigallocatechin-3-Gallate on Breast Cancer Progression via Reducing SCUBE2 Methylation and DNMT Activity

“…Among them, EGCG is the most abundant catechin accounting for 50% of the total amount [31]. Previous study has reported that EGCG was responsible for the beneficial bioactivities of green tea and contributed to various biological processes, including anti-inflammatory, antiviral, antioxidative, and antitumor abilities [32,33,34,35]. In addition, EGCG was validated to possess the therapeutic effects in clinical and animal studies [36,37].…”

Flavonoids in Treatment of Chronic Kidney Disease

“…EGCG ( Figure 2 n) was shown to significantly decrease glomerular and tubulointerstitial injury in immune-mediated glomerulonephritis by inhibiting MAPK pathways and phosphorylation of extracellular signal-regulated kinase (ERK)1/2 [ 188 ]. EGCG attenuated FSGS through the suppression of oxidant stress and cell apoptosis by inhibiting the hypoxia inducible factor 1 subunit alpha (HIF-1α)/angiopoietin like 4 (ANGPTL4) pathway [ 189 ]. Icariin ( Figure 2 o) treatment ameliorated renal damage in IgAN rats by the inactivation of the NF-κB pathway and the NLRP3 inflammasome [ 190 ].…”