Resveratrol Alleviates Inflammatory Responses and Oxidative Stress in Rat Kidney Ischemia-Reperfusion Injury and H2O2-Induced NRK-52E Cells via the Nrf2/TLR4/NF-κB Pathway

Abstract

Background: Ischemia-reperfusion injury (IRI) is one of the major causes of postoperative renal allograft dysfunction, which is mainly the result of proinflammatory reactions including inflammatory responses, oxidative stress, and metabolic disorders. Resveratrol (RSV) plays an important role in protecting various organs in IRI because it reduces oxidative stress, lessens the inflammatory response, and exerts anti-apoptotic effects. The aim of this study was to demonstrate the renoprotective effect of RSV in inhibiting inflammatory responses, reducing oxidative stress, and decreasing cell apoptosis in vivo and in vitro. Methods: RSV was administered before renal ischemia and H₂O₂ induction. Serum and kidneys were harvested 24 h after reperfusion and NRK-52E cells were collected 4 h after H₂O₂ stimulation. Serum creatinine and blood urea nitrogen were used to assess renal function. Hematoxylin and eosin staining was performed to assess histological injury. Quantitative real-time PCR and enzyme-linked immunosorbent assay were used to assess proinflammatory cytokine expression. Oxidative stress–related proteins, such as Nrf2 and TLR4, were evaluated by western blot. Terminal deoxynucleotidyl transferase–mediated dUTP-biotin nick end labeling assay was used to detect apoptotic cells in tissues, and western blot was used to evaluate the expression of caspase-3, -8, and -9 in this study. Results: RSV inhibited inflammatory responses and improved renal function after renal IRI. Additionally, RSV decreased oxidative stress and reduced cell apoptosis by upregulating Nrf2 expression, downregulating the TLR4/NF-κB signaling pathway, and by decreasing caspase-3 activity and caspase cascades. Conclusion: Our study demonstrated the mechanisms underlying RSV renoprotection. We found that RSV exerts its greatest effects by blocking inflammatory responses, lowering oxidative stress, and reducing apoptosis via the Nrf2/TLR4/NF-κB pathway.

Maternal Resveratrol Supplementation Prevents Cognitive Decline in Senescent Mice Offspring

“…These findings are consistent with reports in other maternal resveratrol intake interventions in which the offspring presented a decrease in OS levels in nonhuman primates [60], and reduced secretion and expression of pro-inflammatory markers in rodents [61] and humans [55]. It is also important that cognitive improvement in Nrf2-and NF-kβ-levels modulation have been described in SAMP8 after environmental enrichment (EE) [26] and rat kidney ischemia model [62], among others.…”

Health Benefits and Molecular Mechanisms of Resveratrol: A Narrative Review

“…Moreover, resveratrol attenuated inflammation by downregulating high mobility group box 1 (HMGB1) as well as suppressing NF-κB and Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling pathways [41,42]. In addition, both in vitro and in vivo, the anti-inflammatory effects of resveratrol were associated with its inhibition of the toll-like receptor 4 (TLR4)/NF-κB signaling cascade [43,44]. Furthermore, resveratrol attenuated inflammation by inhibiting the activation of NACHT, LRR, and PYD domains-containing protein 3 (NALP3) inflammasome and inducing autophagy via SIRT1 upregulation and AMPK activation [34,35].…”

Redox signaling in aging kidney and opportunity for therapeutic intervention through natural products

“…Resveratrol [131,132], kaempferitrin [133] and chrysin [134] could reduce renal damage through AGE/RAGE or Nrf2-Keap1 in animal models of diabetic nephropathy. Additionally, resveratrol also played paramount roles in protecting against diabetic renal fibrosis [135], aging kidney [66] and kidney damage [136,137] in animal models. Nevertheless, the clinical application of resveratrol remains a tremendous challenge due to the unfavorable pharmacokinetic and biochemical properties, while resveratrol conjugates may portend a novel paradigm in the development of pharmaceutical exploitation, which has been proved to be more efficacious than resveratrol in human neuroblastoma SH-SY5Y cells [138].…”