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Metformin attenuates myocardial remodeling and neutrophil recruitment after myocardial infarction in rat.

Soraya H, Rameshrad M, Mokarizadeh A, Garjani A - Bioimpacts (2015)

Bottom Line: The heart to body weight ratio was also decreased with all doses of metformin.Pre-treatment with metformin decreased post-MI myocardial injuries by reducing cardiac remodeling and myocardial neutrophil activity.The results could be explained as a new mechanism for cardio-protective effect of metformin.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Pharmacology, Faculty of Pharmacy, Urmia University of Medical Sciences, Urmia, Iran.

ABSTRACT

Introduction: Acute treatment with metformin has a cardio-protective effects by suppression of inflammatory responses during myocardial infarction (MI) through activation of AMP-activated protein kinase (AMPK). Neutrophils have a pivotal role during MI-induced inflammatory responses. Some anti-inflammatory treatments have decreased cardiac injury and infarct size in MI. Here we evaluated the effects of chronic pre-treatment with metformin on myocardial remodeling and neutrophil recruitment after isoproterenol-induced MI.

Methods: Male wistar rats were randomly assigned into 6 groups (n=6) of untreated control, sham, isoproterenol (Iso), and pre-treated orally with 25, 50, and 100 mg/kg of metformin, twice daily, for 14 days. Isoproterenol was injected subcutaneously (sc) at 13th and 14th days for induction of acute MI. Histopathological examinations were done on the harvested hearts. Number of neutrophils in peripheral blood and their infiltration to myocardium were evaluated by Gimsa staining and myeloperoxidase (MPO) assay, respectively.

Results: Histopathological analysis showed a significant attenuation of isoproterenol-induced cardiomyocyte necrosis and fibrosis by all three doses of metformin. The heart to body weight ratio was also decreased with all doses of metformin. Pre-treatment with metformin in comparison to Iso (MI) group reduced peripheral neutrophils (p<0.05, p<0.01, and p<0.001 at 25, 50, and 100 mg/kg; respectively) as well as MPO activity (p<0.05 and p<0.01 at 50 and 100 mg/ kg, respectively).

Conclusion: Pre-treatment with metformin decreased post-MI myocardial injuries by reducing cardiac remodeling and myocardial neutrophil activity. The results could be explained as a new mechanism for cardio-protective effect of metformin.

No MeSH data available.


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Mentions: The regularly arranged myocardial fibers with clear striations were observed in the control group ( Figs. 1- 3). Moreover, there was no evidence of necrosis or fibrosis in the control group. The histological sections of the hearts obtained from isoproterenol treated rats showed widespread subendocardial necrosis, hypertrophy, and abundant fibroblastic hyperplasia ( Figs. 1 and 3). Oral administration of metformin at doses of 25, 50, and 100 mg/kg was started 12 days before induction of infarction and continued for two days at an interval of 12 h after first isoproterenol injection, significantly prevented inflammatory responses and myocardial fibrosis and necrosis. It was observed that the chronic pre-treatment with metformin at doses of 25, 50, and 100 mg/kg reduced the isoproterenol-induced necrosis ( Fig. 2) from 3.75±0.2 in dose-dependent manner by 25% (2.8±0.4) (p<0.05), 39% (2.3±0.16) (p<0.01), 52% (1.8±0.38) (p<0.001), and also reduced isoproterenol-induced fibrosis ( Fig. 4) from 3.5±0.2 by 26% (2.5± 0.2), 27% (2.5±0.2) (p<0.01), and 32% (2.3±0.2) (p<0.001), respectively. Metformin alone (sham) had no effect on tissue stricter and histology in normal healthy animals as shown in Figs. 1 and 3.


Metformin attenuates myocardial remodeling and neutrophil recruitment after myocardial infarction in rat.

Soraya H, Rameshrad M, Mokarizadeh A, Garjani A - Bioimpacts (2015)

© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4401166&req=5

Mentions: The regularly arranged myocardial fibers with clear striations were observed in the control group ( Figs. 1- 3). Moreover, there was no evidence of necrosis or fibrosis in the control group. The histological sections of the hearts obtained from isoproterenol treated rats showed widespread subendocardial necrosis, hypertrophy, and abundant fibroblastic hyperplasia ( Figs. 1 and 3). Oral administration of metformin at doses of 25, 50, and 100 mg/kg was started 12 days before induction of infarction and continued for two days at an interval of 12 h after first isoproterenol injection, significantly prevented inflammatory responses and myocardial fibrosis and necrosis. It was observed that the chronic pre-treatment with metformin at doses of 25, 50, and 100 mg/kg reduced the isoproterenol-induced necrosis ( Fig. 2) from 3.75±0.2 in dose-dependent manner by 25% (2.8±0.4) (p<0.05), 39% (2.3±0.16) (p<0.01), 52% (1.8±0.38) (p<0.001), and also reduced isoproterenol-induced fibrosis ( Fig. 4) from 3.5±0.2 by 26% (2.5± 0.2), 27% (2.5±0.2) (p<0.01), and 32% (2.3±0.2) (p<0.001), respectively. Metformin alone (sham) had no effect on tissue stricter and histology in normal healthy animals as shown in Figs. 1 and 3.

Bottom Line: The heart to body weight ratio was also decreased with all doses of metformin.Pre-treatment with metformin decreased post-MI myocardial injuries by reducing cardiac remodeling and myocardial neutrophil activity.The results could be explained as a new mechanism for cardio-protective effect of metformin.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Pharmacology, Faculty of Pharmacy, Urmia University of Medical Sciences, Urmia, Iran.

ABSTRACT

Introduction: Acute treatment with metformin has a cardio-protective effects by suppression of inflammatory responses during myocardial infarction (MI) through activation of AMP-activated protein kinase (AMPK). Neutrophils have a pivotal role during MI-induced inflammatory responses. Some anti-inflammatory treatments have decreased cardiac injury and infarct size in MI. Here we evaluated the effects of chronic pre-treatment with metformin on myocardial remodeling and neutrophil recruitment after isoproterenol-induced MI.

Methods: Male wistar rats were randomly assigned into 6 groups (n=6) of untreated control, sham, isoproterenol (Iso), and pre-treated orally with 25, 50, and 100 mg/kg of metformin, twice daily, for 14 days. Isoproterenol was injected subcutaneously (sc) at 13th and 14th days for induction of acute MI. Histopathological examinations were done on the harvested hearts. Number of neutrophils in peripheral blood and their infiltration to myocardium were evaluated by Gimsa staining and myeloperoxidase (MPO) assay, respectively.

Results: Histopathological analysis showed a significant attenuation of isoproterenol-induced cardiomyocyte necrosis and fibrosis by all three doses of metformin. The heart to body weight ratio was also decreased with all doses of metformin. Pre-treatment with metformin in comparison to Iso (MI) group reduced peripheral neutrophils (p<0.05, p<0.01, and p<0.001 at 25, 50, and 100 mg/kg; respectively) as well as MPO activity (p<0.05 and p<0.01 at 50 and 100 mg/ kg, respectively).

Conclusion: Pre-treatment with metformin decreased post-MI myocardial injuries by reducing cardiac remodeling and myocardial neutrophil activity. The results could be explained as a new mechanism for cardio-protective effect of metformin.

No MeSH data available.


Related in: MedlinePlus