Anti-oxidant effect of metformin through AMPK/SIRT1/PGC-1α/SIRT3– independent GPx1 expression in the heart of mice with endometriosis
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Rodrigo Felgueiras
,
Ana C. Neto
Abstract
Objectives
Endometriosis is a gynecological disease associated with an imbalance between oxidative species production and anti-oxidative defenses. In women, endometriosis has been reported to associate with increased incidence of cardiovascular events. As such, this study aimed to analyze the oxidation-responsive AMPK/SIRT1/PGC-1α/SIRT3 pathway in the heart of a mouse model of endometriosis. The effect of metformin, an insulin-sensitizing and anti-oxidative drug with already shown positive results in endometriotic tissue was studied.
Methods
Thirty-six female B6CBA/F1 mice were divided into 4 groups (Control-C, Surgery-induced Endometriosis and Metformin-EM (50 mg/kg/day orally administrated for 3 months), Endometriosis-E and Metformin-M). Immunofluorescent labelling of SIRT1 and SIRT3 was performed in the heart tissue. Assessment of expression of AMPKα, SIRT1, PGC-1α, SIRT3, SOD2, and GPx1 was performed by Western Blotting. The quantification of microRNA(miR)-34a, miR-195, miR-217, miR-155 and miR-421, involved in the regulation of expression of SIRT1 and SIRT3, was performed by Real-Time PCR.
Results
Data showed an increase in phospho-AMPKα and in GPx1 expression in the EM group when compared to the C group, but not in the total AMPK, SIRT1, PGC-1α, SIRT3 and SOD2, suggesting a GPx1 expression increase independently of the AMPK/SIRT1/PGC-1α/SIRT3 pathway. MicroRNAs, excepting miR-217, showed a consistent trend of increase in the M group.
Conclusions
Our study showed that endometriosis does not significantly affect the expression of the components of the AMPK/SIRT1/PGC-1α/SIRT3 pathway in the heart. However, it indicates that an oxidative condition underlying endometriosis is required for metformin to evidence an increment in the expression of the anti-oxidative enzyme GPx1.
Acknowledgments
We thank Dr. José Pedro Barbosa (Department of Community Medicine, Information and Decision in Health, Faculty of Medicine of University of Porto–Portugal), for his aid and overview of statistical analysis.
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Research funding: The research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
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Author contributions: Rodrigo Felgueiras: Data obtaining and curation, Writing – Original draft preparation. A Catarina Neto: Conceptualization and preparation of the animal model. Data curation. Adriana R. Rodrigues: Data curation. Alexandra M. Gouveia: Writing – Reviewing. Henrique Almeida: Writing-Reviewing and Supervision. Delminda Neves: Writing – Reviewing and Supervision.
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Competing interests: Authors state no conflict of interest.
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Informed consent: Not applicable.
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Ethical approval: The use of experimental animals was approved by the i3S Animal Ethics Committee (internal reference-2018/27) and the Portuguese Competent Authority (DGAV–Direcção-Geral de Alimentação e Veterinária).
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© 2022 Walter de Gruyter GmbH, Berlin/Boston
Articles in the same Issue
- Frontmatter
- Letter to the Editor
- COVID-19 pandemic: transmission of SARS-CoV-2 in animals, a risk for human beings
- Original Articles
- Anti Mullerian hormone as a diagnostic tool for polycystic ovary syndrome in women of reproductive age with morbid obesity
- Potential tumor marker for hepatocellular carcinoma identification: PI3K and pro-inflammatory cytokines (TGF-β, IL-1, and IL-6)
- The investigation of the frequency of the alpha-1-antitrypsin phenotype in patients with liver cirrhosis
- Anti-oxidant effect of metformin through AMPK/SIRT1/PGC-1α/SIRT3– independent GPx1 expression in the heart of mice with endometriosis
- Hypoxia-inducible factor-1α and ischemia-modified albumin levels in intensive care COVID-19 Patients
- Association between TP53 Arg72Pro variant and recurrent pregnancy loss in the Greek population
- Selective estrogen receptor α and β antagonist aggravate cardiovascular dysfunction in type 2 diabetic ovariectomized female rats
- Adrenocorticotropic hormone (ACTH) level and adrenal deficiency in patients with mucocutaneous pemphigus
- The effect of resistance training on serum levels of sex hormones and sperm quality in male rats under X-ray radiation
- The effect of high-intensity interval training on serum and adipose tissues vaspin levels in rats fed a high-fat high-sucrose diet
- Anti-migratory effect of curcumin on A-549 lung cancer cells via epigenetic reprogramming of RECK/ matrix metalloproteinase axis
- Efficacy of rectal progesterone on maternal and neonatal outcomes in pregnant women with Preterm Premature Rupture of membranes: a triple-blind randomised clinical trial
- Case Report
- Ovarian tissue cryopreservation in Malaysia: a case series
- Review Articles
- An overview of prognostic value of neurologic and cardiac biomarkers in patients with COVID-19 sequelae
- Potential role of melatonin in prevention and treatment of lung cancer
- Esketamine–A quick-acting novel antidepressant without the disadvantages of ketamine
Articles in the same Issue
- Frontmatter
- Letter to the Editor
- COVID-19 pandemic: transmission of SARS-CoV-2 in animals, a risk for human beings
- Original Articles
- Anti Mullerian hormone as a diagnostic tool for polycystic ovary syndrome in women of reproductive age with morbid obesity
- Potential tumor marker for hepatocellular carcinoma identification: PI3K and pro-inflammatory cytokines (TGF-β, IL-1, and IL-6)
- The investigation of the frequency of the alpha-1-antitrypsin phenotype in patients with liver cirrhosis
- Anti-oxidant effect of metformin through AMPK/SIRT1/PGC-1α/SIRT3– independent GPx1 expression in the heart of mice with endometriosis
- Hypoxia-inducible factor-1α and ischemia-modified albumin levels in intensive care COVID-19 Patients
- Association between TP53 Arg72Pro variant and recurrent pregnancy loss in the Greek population
- Selective estrogen receptor α and β antagonist aggravate cardiovascular dysfunction in type 2 diabetic ovariectomized female rats
- Adrenocorticotropic hormone (ACTH) level and adrenal deficiency in patients with mucocutaneous pemphigus
- The effect of resistance training on serum levels of sex hormones and sperm quality in male rats under X-ray radiation
- The effect of high-intensity interval training on serum and adipose tissues vaspin levels in rats fed a high-fat high-sucrose diet
- Anti-migratory effect of curcumin on A-549 lung cancer cells via epigenetic reprogramming of RECK/ matrix metalloproteinase axis
- Efficacy of rectal progesterone on maternal and neonatal outcomes in pregnant women with Preterm Premature Rupture of membranes: a triple-blind randomised clinical trial
- Case Report
- Ovarian tissue cryopreservation in Malaysia: a case series
- Review Articles
- An overview of prognostic value of neurologic and cardiac biomarkers in patients with COVID-19 sequelae
- Potential role of melatonin in prevention and treatment of lung cancer
- Esketamine–A quick-acting novel antidepressant without the disadvantages of ketamine
