Melatonin prevents sepsis-induced renal injury via the PINK1/Parkin1 signaling pathway

Dai,Wenling; Huang,Haifeng; Si,Linjie; Hu,Shi; Zhou,Liangliang; Xu,Lingling; Deng,Yijun

doi:10.3892/ijmm.2019.4306

Melatonin prevents sepsis-induced renal injury via the PINK1/Parkin1 signaling pathway

Authors:
- Wenling Dai
- Haifeng Huang
- Linjie Si
- Shi Hu
- Liangliang Zhou
- Lingling Xu
- Yijun Deng
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Affiliations: Department of Critical Care Medicine, Yancheng City No. 1 People's Hospital, Yancheng, Jiangsu 224006, P.R. China, Department of Clinical Laboratory, Sheyang Zhenyang Hospital, Yancheng, Jiangsu 224300, P.R. China, Department of Clinical Laboratory, Yancheng City No. 1 People's Hospital, Yancheng, Jiangsu 224006, P.R. China
Published online on: August 7, 2019 https://doi.org/10.3892/ijmm.2019.4306
Pages: 1197-1204
Copyright: © Dai et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Melatonin (N‑acetyl‑5‑methoxytryptamine; MT) has been shown to have a protective effect against sepsis‑induced renal injury, however, the mechanisms underlying the function of MT remain to be elucidated. Therefore, in the present study, the potential mechanisms underlying the preventive role of MT in sepsis‑induced renal injury were investigated. Hematoxylin and eosin staining was used to detect the effect of MT on the reduction of renal tissue damage, and immunohistochemistry (IHC), ELISA and western blot analysis were performed to determine the influence of MT on the protein expression of PTEN‑induced putative kinase 1 (PINK1), nucleotide‑oligomerization binding domain and leucine‑rich repeat pyrin domain‑containing 3 (NLRP3), apoptosis‑associated speck‑like protein containing a C‑terminal caspase recruitment domain (ASC1), interleukin (IL)‑18, IL‑1β, IL‑6 and cleaved caspase‑1. Finally, a TUNEL assay was used to compare the rate of apoptosis of renal tissues among the sham, cecal ligation and puncture (CLP), and CLP + MT groups. The extent of tissue damage in the CLP group was the highest and the extent of tissue damage in the sham group was the lowest. The IHC and western blot analysis showed that the sham group had the highest protein level of PINK1, whereas the CLP group had the lowest protein level of PINK1. By contrast, the sham group had the lowest protein level of NLRP, whereas the CLP group had the highest level of NLRP3. Furthermore, CLP treatment enhanced the protein expression of ASC1 and cleaved caspase‑1, whereas the administration of MT reduced the protein expression of ASC1 and cleaved caspase‑1 to a certain degree. Finally, the apoptotic rate was found to be the highest in the CLP group and the lowest in the sham group. Taken together, in evaluating the therapeutic effect of MT on sepsis‑induced renal injury, the results of the present study showed that MT alleviated sepsis‑induced renal injury by regulating the expression of PINK1, Parkin1, NLRP3, ASC and cleaved caspase‑1 in rats.

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