Green tea (Camellia sinensis) Attenuates Nephropathy by Downregulating Nox4 NADPH Oxidase in Diabetic Spontaneously Hypertensive Rats

Abstract

Green tea (GT), through its antioxidant properties, may be useful to treat or prevent human diseases. Because several lines of evidence suggest that oxidative stress contributes to the pathogenesis of diabetic nephropathy, we tested the hypothesis that GT prevents diabetes and hypertension-related renal oxidative stress, attenuating renal injury. Spontaneously hypertensive rats (SHR) with streptozotocin-induced diabetes and nondiabetic SHR were treated daily with tap water or freshly prepared GT (13.3 g/L). After 12 wk, the systolic blood pressure did not differ between treated and untreated nondiabetic or diabetic rats. However, body weight was less (P < 0.05) and glycemia was greater in diabetic SHR rats than in nondiabetic rats. Renal oxidative stress variables such as 8-hydroxy-2'-deoxyguanosine (8-OHdG) and nitrotyrosine expression, NADPH oxidase-dependent superoxide generation, and the expression of renal cortex Nox4 were greater (P < 0.05) in diabetic rats that received water (DW) than in nondiabetic rats that received water (CW). The 8-OHdG and NADPH oxidase-dependent superoxide generation were significantly less in rats treated with GT. Nitrotyrosine and Nox4 expression were significantly less in diabetic rats that received GT (DGT) than in DW. Likewise, the indices of renal injury, albuminuria, and renal expression of collagen IV were significantly greater in DW than in CW. These differences were significantly less in DGT than in DW. GT reestablished the redox state and reduced the indicators of nephropathy without altering glycemia and blood pressure levels in diabetic SHR. These findings suggest that the consumption of GT may ameliorate nephropathy in diabetic hypertensive patients.

The contribution of hypertension to diabetic nephropathy and retinopathy: the role of inflammation and oxidative stress

“…67,[85][86][87][88][93][94][95][97][98][99]156 Finally, in experimental diabetes, the use of green tea was associated with an improvement in diabetic nephropathy and retinopathy and associated with a reduction in oxidative stress. 91, 157 The usefulness of these dietary approaches in diabetic patients with hypertension and nephropathy or retinopathy that are on standard treatment deserves to be tested in larger clinical trials. Finally, a better understanding and identification of the basic mechanism of action of different antioxidants in diabetes can lead to better optimization of renal and retinal protection.…”

“…90 In a different study, it was found that longterm green tea consumption ameliorates renal injury in hypertensive diabetic rats by inhibiting oxidative stress through downregulation of Nox4 expression. 91 The presence of hypertension exacerbates retinopathy in diabetic animals. We have demonstrated that the concomitance of both diabetes and hypertension leads to earlier and more pronounced retinal inflammatory alterations characterized by increased expression levels of ICAM-1, VEGF and NF-kB p65 in the retina when compared with those of normotensive diabetic rats.…”

Inhibition to DRP1 translocation can mitigate p38 MAPK-signaling pathway activation in GMC induced by hyperglycemia

“…Previous studies revealed that ECM accumulation in DN is closely associated with the activation of the p38 MAPK-signaling pathway, oxidative stress, and mitochondrial dysfunction. 16,[37][38][39][40][41] Therefore, we predict that the abnormality of DRP1 affects mitochondrial function, and further influences p38 MAPK-signaling pathways, thus affecting DN.…”

Inactivation of AMPK Mediates High Phosphate-Induced Extracellular Matrix Accumulation via NOX4/TGFß-1 Signaling in Human Mesangial Cells

“…The samples and Western blots were prepared as described in previous studies [23,24,25]. The following primary antibodies were used: goat anti-type IV collagen (1:500, Southern Biotech, Birmingham, AL), goat anti-fibronectin (F/N) (1:500, EMD Millipore, Billerica, MA), rabbit anti-NOX4 (1:500, Santa Cruz Biotechnology, Danvers, MA), rabbit anti-alpha smooth muscle actin (α-SMA) (1:500, Abcam, Cambridge, MA), rabbit phosphorylated AMPK (Thr 172 ) and LKB1 (Ser 428 ) (1:1000, Cell Signalling Technology, Danvers, MA), rabbit total AMPK and LKB1 (1:1000, Cell Signalling Technology), rabbit phosphorylated SMAD3 (1:500, Cell Signalling Technology, Danvers, MA), and total rabbit SMAD3 (1:1000, Cell Signalling Technology, Danvers, MA).…”