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

doi:10.1080/13813455.2020.1869265

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

Cardiovascular Sciences

Research output: Contribution to journal › Article › peer-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 language	English
Pages (from-to)	734-740
Number of pages	7
Journal	Archives of Physiology and Biochemistry
Volume	129
Issue number	3
Early online date	13 Jan 2021
DOIs	https://doi.org/10.1080/13813455.2020.1869265
Publication status	Published - 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)

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1080/13813455.2020.1869265

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Al-Ani, B., Alzamil, N. M., Hewett, P. W., Al-Hashem, F., Bin-Jaliaha, I., Shatoor, A. S., Kamar, S. S., Latif, N. S. A., Haidara, M. A., & Dawood, A. F. (2023). Metformin ameliorates ROS-p53-collagen axis of fibrosis and dyslipidemia in type 2 diabetes mellitus-induced left ventricular injury. Archives of Physiology and Biochemistry, 129(3), 734-740. https://doi.org/10.1080/13813455.2020.1869265

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title = "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 = "cardiac injury, Diabetes, metformin, rat model, ROS-p53-collagen axis",

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

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: {\textcopyright} 2021 Informa UK Limited, trading as Taylor & Francis Group.",

year = "2023",

doi = "10.1080/13813455.2020.1869265",

language = "English",

volume = "129",

pages = "734--740",

journal = "Archives of Physiology and Biochemistry",

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Al-Ani, B, Alzamil, NM, Hewett, PW, Al-Hashem, F, Bin-Jaliaha, I, Shatoor, AS, Kamar, SS, Latif, NSA, Haidara, MA & Dawood, AF 2023, 'Metformin ameliorates ROS-p53-collagen axis of fibrosis and dyslipidemia in type 2 diabetes mellitus-induced left ventricular injury', Archives of Physiology and Biochemistry, vol. 129, no. 3, pp. 734-740. https://doi.org/10.1080/13813455.2020.1869265

TY - JOUR

T1 - Metformin ameliorates ROS-p53-collagen axis of fibrosis and dyslipidemia in type 2 diabetes mellitus-induced left ventricular injury

AU - Al-Ani, Bahjat

AU - Alzamil, Norah M.

AU - Hewett, Peter W.

AU - Al-Hashem, Fahaid

AU - Bin-Jaliaha, Ismaeel

AU - Shatoor, Abdullah S.

AU - Kamar, Samaa S.

AU - Latif, Noha S. Abdel

AU - Haidara, Mohamed A.

AU - Dawood, Amal F.

N1 - 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.

PY - 2023

Y1 - 2023

N2 - 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.

AB - 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.

KW - cardiac injury

KW - Diabetes

KW - metformin

KW - rat model

KW - ROS-p53-collagen axis

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U2 - 10.1080/13813455.2020.1869265

DO - 10.1080/13813455.2020.1869265

M3 - Article

C2 - 33439743

AN - SCOPUS:85099419789

SN - 1381-3455

VL - 129

SP - 734

EP - 740

JO - Archives of Physiology and Biochemistry

JF - Archives of Physiology and Biochemistry

IS - 3

ER -

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

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

UN SDGs

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