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

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.

Keywords:

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

Disclosure statement

The authors declare the absence of any conflicts of interest.

Data availability statement

The data that support the findings of this study are available on request from the corresponding author, [A.F. Dawood]. The data are not publicly available due to confidential handling of our materials because this manuscript data is part of a big project which is underway.

Additional information

Funding

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].