Isoflurane induces liver injury by modulating the expression of miR-125a-5p

Clin Res Hepatol Gastroenterol. 2021 Sep;45(5):101732. doi: 10.1016/j.clinre.2021.101732. Epub 2021 Jun 15.

Abstract

Background: Isoflurane can cause hepatotoxicity, and microRNAs (miRNAs) are involved in the regulation of liver injury. Therefore, this study aimed to explore the effect of miR-125a-5p on isoflurane-induced liver injury.

Basic procedures: Sprague-Dawley (SD) male rats and BRL-3A cells were exposed to isoflurane to construct animal and cell models. Serum alanine transaminase (ALT) and aspartate transaminase (AST) levels of rats were detected. RT-qPCR was performed for the measurement of miR-125a-5p levels. Cell proliferation and apoptosis were also detected.

Main findings: After isoflurane treatment, serum ALT and AST levels of rats increased in a time-dependent manner, and the differences reached significant levels from 3 days after isoflurane treatment. MiR-125a-5p levels increased significantly in the liver tissues of isoflurane-treated rats. MiR-125a-5p downregulation significantly attenuated isoflurane-induced increasing trend of serum ALT and AST levels in rats. In BRL-3A cells, isoflurane treatment significantly inhibited cell proliferation and promoted cell apoptosis, which was reversed by miR-125a-5p downregulation.

Principal conclusions: Isoflurane exposure significantly elevates the level of miR-125a-5p in the liver tissues of rats. Downregulation of miR-125a-5p may protect against isoflurane-induced liver injury through regulating liver cell proliferation and apoptosis. Dysregulation of miR-125a-5p might be a possible mechanism of isoflurane-induced liver injury.

Keywords: Apoptosis; Downregulation; Isoflurane; Liver; MiR-125a-5p; Proliferation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Cell Proliferation
  • Chemical and Drug Induced Liver Injury, Chronic*
  • Isoflurane* / toxicity
  • Male
  • MicroRNAs* / genetics
  • Rats
  • Rats, Sprague-Dawley

Substances

  • MicroRNAs
  • Isoflurane