Epigallocatechin-3-gallate (EGCG), extracted from green tea, has been shown to have antioxidative activity. In the present study, we evaluated the effect of EGCG on the kidney function in db/db mice and also tried to investigate the underlying mechanism of the renoprotective effects of EGCG in both animals and cells. EGCG treatment could decrease the level of urinary protein, 8-iso-PGF2a, and Ang II. Moreover, EGCG could also change the level of several parameters associated with oxidative stress. In addition, the protein expression levels of AT-1R, p22-phox, p47-phox, p-ERK1/2, p-p38 MAPK, TGF-β1, and α-SMA in diabetic db/db mice were upregulated, and all of these symptoms were downregulated with the treatment of EGCG at 50 and 100 mg/kg/d. Furthermore, the pathological changes were ameliorated in db/db mice after EGCG treatment. HK-2 cell-based experiments indicated that EGCG could inhibit the expression of MAPK pathways, which is the downstream effector of Ang II mediated oxidative stress. All these results indicated that EGCG treatment could ameliorate changes of renal pathology and delay the progression of DKD by suppressing hyperglycemia-induced oxidative stress in diabetic db/db mice.

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To explore whether epigallocatechin-3-gallate (EGCG) improves renal damage in diabetic db/db mice and high-glucose- (HG-) induced injury in HK-2 cells by regulating the level of Klotho gene promoter methylation. Western blotting was used to detect the protein expression levels of DNA methyltransferase 1 (DNMT1), DNMT3a, DNMT3b, transforming growth factor-β1 (TGF-β1), α-smooth muscle actin (α-SMA), and Klotho. The methylation level of the Klotho gene promoter was detected by pyrosequencing. Chromatin immunoprecipitation was used to detect the binding of the Klotho gene promoter to DNMT1 and DNMT3a. The expression of oxidative stress markers (reactive oxygen species (ROS), superoxide dismutase (SOD), malondialdehyde (MDA), catalase (CAT), and 8-hydroxy-2′-deoxyguanosine (8-OHdG)) and inflammatory cytokines (interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α (TNF-α)) in kidney homogenates was also measured using ELISA. Klotho and DNMT3b protein expression was upregulated, while DNMT1, DNMT3a, TGF-β1, and α-SMA protein expression was downregulated after EGCG treatment. EGCG treatment also reduced the methylation level of the Klotho gene promoter as well as the binding of DNMT3a to the Klotho gene promoter. In addition, EGCG treatment significantly decreased the levels of ROS, MDA, 8-OHdG, IL-1β, IL-6, and TNF-α and increased the levels of CAT and SOD. Under HG conditions, EGCG regulated Klotho gene promoter methylation via DNMT3a and decreased the methylation level of the Klotho gene promoter, thereby upregulating the expression of the Klotho protein to exert its protective effect.

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Objective To assess whether febuxostat use increases the risk of developing cardiovascular events, death from cardiac-cause and all-cause mortalities. Methods The relevant literature was searched in several databases including the MEDLINE (PubMed, 1 Jan. 1966–29 Feb. 2020), Web of science, EMBASE (1 Jan. 1974–29 Feb. 2020), ClinicalTrials.gov and Cochrane Central Register for Controlled Trials. Manual searches for references cited in the original studies and relevant review articles were also performed. All studies included in this metanalysis were published in English. Results In the end, 20 studies that met our inclusion criteria were included in this meta-analysis. Use of febuxostat was found not to be associated with an increased risk of all-cause mortality (RR = 0.87, 95% CI 0.57–1.32, P =0.507). Also, there was no association between febuxostat use and mortalities arising from cardiovascular diseases (CVD) (RR = 0.84, 95% CI 0.49–1.45, P=0.528). The RR also revealed that febuxostat use was not associated with CVD events (RR = 0.98, 95% CI 0.83–1.16, P =0.827). Furthermore, the likelihood of occurrence of CVD events was found not to be dependent on febuxostat dose (RR = 1.04, 95% CI 0.84–1.30, P =0.723). Conclusion Febuxostat use is not associated with increased risks of all-cause mortality, death from CVD or CVD events. Accordingly, it is a safe drug for the treatment of gout. Systematic review registration: PROSPERO CRD42019131872