Metformin ameliorates ROS-p53-collagen axis of fibrosis and dyslipidemia in type 2 diabetes mellitus-induced left ventricular injury

Bahjat Al-Ani, Norah M. Alzamil, Peter W. Hewett, Fahaid Al-Hashem, Ismaeel Bin-Jaliaha, Abdullah S. Shatoor, Samaa S. Kamar, Noha S. Abdel Latif, Mohamed A. Haidara, Amal F. Dawood*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Background: The link between oxidative stress (ROS), apoptosis (p53) and fibrosis (collagen) in type 2 diabetes mellitus (T2DM)-induced cardiac injury in the presence and absence of the antidiabetic drug, metformin has not been investigated before.

Material and methods: T2DM was induced in rats by a combination of high carbohydrate and fat diets (HCFD) and streptozotocin (50 mg/kg) injection. The protection group started metformin (200 mg/kg) treatment 14 days prior to the induction of diabetes and continued on metformin and HCFD until being sacrificed at week 12.

Results: Diabetes significantly induced blood levels of ROS and left ventricular p53 and collagen expression that was inhibited by metformin. Metformin also significantly reduced glycated haemoglobin and dyslipidemia induced by diabetes. In addition, a significant correlation between ROS-p53-collagen axis and glycaemia and hyperlipidaemia was observed.

Conclusions: These findings show that metformin provides substantial protection against diabetic cardiomyopathy-induced ROS-p53 mediated fibrosis and dyslipidemia.

Original languageEnglish
Pages (from-to)734-740
Number of pages7
JournalArchives of Physiology and Biochemistry
Volume129
Issue number3
Early online date13 Jan 2021
DOIs
Publication statusPublished - 2023

Bibliographical note

Funding Information:
The current research project received funding from Health Sciences Research Centre, King Abdullah bin Abdulaziz University Hospital, Princess Nourah bint Abdulrahman University, through Research Funding Program, grant No [G18-00006].

Publisher Copyright:
© 2021 Informa UK Limited, trading as Taylor & Francis Group.

Keywords

  • cardiac injury
  • Diabetes
  • metformin
  • rat model
  • ROS-p53-collagen axis

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

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