The use of glutathione to reduce oxidative stress status and its potential for modifying the extracellular matrix organization in cleft lip

Rong Li, Chen Huang, Jeff Cheuk Hin Ho, Cherry Chi Tim Leung, Richard Yuen Chong Kong, Yu Li, Xiao Liang, Keng Po Lai, William Ka Fai Tse

Research output: Contribution to journalArticlepeer-review

Abstract

Objective: Cleft lip (CL) is a common congenital anomaly that can be syndromic or non-syndromic. It can be triggered by the mutation of gene or environmental factors. The incidence of CL is about 1 out of 700 live births. Facial development is a complex process, and there is no existing therapy to prevent the disease development. One of the characteristics in this facial malformation is the increased presence of reactive oxygen species (ROS). In this study, we hypothesize that the antioxidant glutathione (GSH) could help to attenuate the oxidative stress in this disease. Methods: Bioinformatics network pharmacology was applied to determine pharmacological targets and molecular mechanisms of GSH treatment for CL. Moreover, RNA-sequencing of the POLR1C knockdown osteoblast CL model was applied to validate the in silico data of using GSH in CL. Results: Twenty-two core targets of GSH and CL were identified via various bioinformatics tools. The GO and KEGG analysis indicated that GSH could modulate two major families (matrix metalloproteinase and integrins), which are related to extracellular matrix modification and composition for facial development in CL. The findings from POLR1C knockdown model further supported the rescue response of GSH in CL. Conclusions: The study uncovered the possible pharmacological mechanism of GSH for treating CL. The data helps research group to focus on the specific pathways for understanding the biological action of GSH for treating the CL in the future.

Original languageEnglish
Pages (from-to)130-138
Number of pages9
JournalFree Radical Biology and Medicine
Volume164
DOIs
Publication statusPublished - Feb 20 2021

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Physiology (medical)

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