Fasudil may alleviate alcohol-induced astrocyte damage by modifying lipid metabolism, as determined by metabonomics analysis

PeerJ. 2023 Jun 6:11:e15494. doi: 10.7717/peerj.15494. eCollection 2023.

Abstract

Alcohol dependence is a chronic, relapsing encephalopathy characterized by compulsive craving for alcohol, loss of control over alcohol use, and the presence of negative emotions and physical discomfort when alcohol is unavailable. Harmful use of alcohol is one of the greatest risk factors for death, illness, and disability. Rho kinase inhibitors have neuroprotective effects. This study used metabonomics analysis to assess untreated astrocytes, astrocytes exposed to 75 mmol/L of alcohol, and astrocytes exposed to 75 mmol/L of alcohol and treated with 15 µg/mL fasudil for 24 h. One of the clearest differences between the alcohol-exposed and fasudil-treated alcohol-exposed groups was the abundance of lipids and lipid-like molecules, although glycerophospholipid metabolism was comparable in both groups. Our findings show that fasudil may alleviate alcohol-induced astrocyte damage by modifying lipid metabolism, providing a new approach for preventing and treating alcohol dependence.

Keywords: Alcohol; Astrocytes; Fasudil; Lipid metabolism; Metabolomics; ROCK pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alcoholism* / complications
  • Astrocytes*
  • Ethanol / adverse effects
  • Humans
  • Lipid Metabolism
  • Metabolomics

Substances

  • fasudil
  • Ethanol

Grants and funding

Xunzhong Qi received funding from the Doctoral Initiation Project of Jiamusi University (grant numbers: JMSUBZ2019-06) and the Talent training project for basic scientific research of Heilongjiang Province Educational Commission of China (grant numbers: 2019-KYYWF-1357). Xiaofeng Zhu received funding from The National Key R&D Program of China (grant numbers: 2018YFC1314404), the Shunjie Bai received funding from the National Key R&D Program of China (grant numbers: 2018YFC1314404); National Natural Science Foundation of China (grant numbers:81901398), and the Natural Science Foundation of Chongqing, China (grant numbers: cstc2019jcyj-msxmX0025). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.