Resveratrol ameliorates renal injury in spontaneously hypertensive rats by inhibiting renal micro-inflammation

Abstract

SynopsisMicro-inflammation plays an important role in the pathogenesis of spontaneously hypertensive rat (SHR). In the present study, we investigated the therapeutic potential of resveratrol (RSV), a polyphenol with anti-fibrosis activity in hypertensive renal damage model. In SHR renal damage model, RSV treatment blunted the increase in urine albumin excretion, urinary β 2 -microglobulin (β 2 -MG), attenuated the decrease in creatinine clearance rate (CCR). The glomerular sclerosis index (1.54 + − 0.33 compared with 0.36 + − 0.07) and tubulointerstitial fibrosis (1.57 + − 0.31 compared with 0.19 + − 0.04) were significantly higher in SHRs compared with Wistar Kyoto rats (WKYs), which were significantly lower by RSV treatment. The increases in mesangium accumulation and the expression of renal collagen type I (Col I), fibronectin (Fn), plasminogen activator inhibitor-1 (PAI-1) and transforming growth factor-β1 (TGF-β1) in SHR were also reduced by RSV treatment. Nuclear factor κB (NF-κB) expression was increased in the cytoplasm and nuclei of the SHR kidneys, which was significantly decreased by RSV treatment. Furthermore, the protein level of IκB-α significantly decreased in the kidneys of the SHR when compared with the WKYs. RSV treatment partially restored the decreased IκB-α level. In SHR kidney, increased expression of interleukin-6 (IL-6), intercellular adhesion molecule-1 (ICAM-1) and monocyte chemoattractant protein 1 (MCP-1) were observed. These changes were attenuated by RSV treatment. No changes in blood pressure were detected between SHR group and SHR + RSV group. Taken together, the present study demonstrated that RSV treatment may significantly attenuate renal damage in the SHR model of chronic kidney disease (CKD). The renal protective effect is associated with inhibition of IL-6, ICAM-1 and MCP-1 expression via the regulation of the nuclear translocation of NF-κB, which suggesting that micro-inflammation may be a potential therapeutic target of hypertensive renal damage.Key words: inflammation, intercellular adhesion molecule-1 (ICAM-1), interleukin-6 (IL-6), monocyte chemoattractant protein 1 (MCP-1), nuclear factor κB (NF-κB), resveratrol (RSV), spontaneously hypertensive rat (SHR).

Anti-Renal Fibrotic Effect of Exercise Training in Hypertension

“…Chronic inflammation was an important feature in the initiation and progression of hypertensive kidney disease [ 10 , 11 ]. Notably, both animal and human studies reported that elevated IL-6 expression levels contribute to the pathogenesis of chronic kidney disease in hypertension [ 7 ].…”

“…Another study showed that renal cortical expression of cyclooxygenase-2 (COX-2) was upregulated in a salt -induced hypertension diet that may play a role in the pathogenesis of hypertensive renal injury [ 9 ]. This indicates that the activation of leukocytes and certain cytokines propagate a state of chronic inflammation in hypertensive nephropathy patients, which likely contributes to the progression of chronic kidney disease and end-stage renal disease [ 10 , 11 ].…”

BCL6 attenuates renal inflammation via negative regulation of NLRP3 transcription

“… 10 Inhibiting renal inflammation attenuates renal injury in SHR. 5 There seems every reason to believe that the protective role of BCL6 in attenuating the Ang II-induced HK-2 cell injury may at least partially attribute to the attenuation of NLRP3 inflammasome activation and inflammation. It is noted that BCL6 also repressed the LPS-induced upregulation of NLRP3 and mature IL-1 β in HK-2 cells, suggesting that the anti-inflammation effect of BCL6 is not limited to the Ang II-induced inflammation.…”

“… 4 Resveratrol ameliorates renal injury by inhibiting renal inflammation in SHR. 5 Angiotensin (Ang) II is a pro-inflammatory cytokine, which is one of the main mechanisms involved in hypertension-induced tissue damage. 6 , 7 Renal inflammation has an important role in the development of hypertension and may be a target for attenuating hypertension.…”

Helix B surface peptide reduces sepsis‐induced kidney injury via PI3K/Akt pathway

“…The degree of kidney tubular interstitial injury was assessed by calculating the proportion of areas with dilatation/flattening of kidney tubules, loss of brush boundary, formation of tubular cast, tubular degeneration and vacuolation. Marking standards were scored from 0 to 4 (normal structure scores 0; ≤25% of areas injured scores 1; 26%‐50% of areas injured scores 2; 51%‐75% of areas injured scores 3; >75% of areas injured scores 4).…”