Resveratrol ameliorates sepsis‑induced acute kidney injury in a pediatric rat model via Nrf2 signaling pathway

Wang,Yan; Feng,Fenling; Liu,Minna; Xue,Jiahong; Huang,Huimei

doi:10.3892/etm.2018.6533

Resveratrol ameliorates sepsis‑induced acute kidney injury in a pediatric rat model via Nrf2 signaling pathway

Authors:
- Yan Wang
- Fenling Feng
- Minna Liu
- Jiahong Xue
- Huimei Huang
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Affiliations: Department of Pediatrics, Ninth Hospital of Xi'an, Xi'an, Shaanxi 710054, P.R. China, Department of Pediatrics, Qikang Hospital of Chinese Traditional and Western Medicine, Xi'an, Shaanxi 710000, P.R. China, Department of Pediatrics, Northwest Women and Children's Hospital, Xi'an, Shaanxi 710061, P.R. China, Department of Pediatrics, The Affiliated Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi 710000, P.R. China, Department of Pediatrics, Xi'an Children's Hospital, Xi'an, Shaanxi 710000, P.R. China
Published online on: July 27, 2018 https://doi.org/10.3892/etm.2018.6533
Pages: 3233-3240

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Abstract

Acute kidney injury (AKI) is a hyper‑inflammation‑induced abrupt loss of kidney function and has become a major public health problem. The cecal ligation and puncture (CLP) model of peritonitis in rat pups mimics the development of sepsis‑induced pediatric AKI is pre‑renal without morphological changes of the kidneys and high lethality. Resveratrol, a natural polyphenolic compound with low toxicity, has obvious anti‑oxidant and anti‑inflammatory properties. The present study aimed to determine whether resveratrol alleviates pediatric AKI and investigated the potential mechanism. Thus, a CLP model of 17‑18 day‑old rat pups was used to mimic the development of sepsis‑induced AKI in children. In the group treated with resveratrol, renal injury induced by CLP was alleviated with downregulation of tumor necrosis factor (TNF)‑α, interleukin (IL)‑1β and kidney injury molecule (KIM)‑1 expression. Nuclear factor‑erythroid‑2‑related factor 2 (Nrf2) signaling is known to effectively inhibit inflammation, the present study found that resveratrol reduced the lipopolysaccharide‑induced inflammatory response in kidney cells in vitro and induced the activation of Nrf2 signaling, including accumulation of nuclear Nrf2 and increase of the expression of Nrf2 target genes heme oxygenase (HO)‑1 and NAD(P)H dehydrogenase (quinone) 1 (NQO1); this was confirmed by the induction of the expression of HO‑1 and NQO1 by treatment of resveratrol in vitro and in vivo. Of note, knockdown of Nrf2 effectively abrogated the downregulation of TNF‑α, IL‑1β and KIM‑1 expression induced by resveratrol in vitro. These results suggested that resveratrol ameliorates sepsis‑induced acute kidney injury in a pediatric model of AKI via the Nrf2 signaling pathway.

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