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Metformin alleviates monoamine oxidase-related vascular oxidative stress and endothelial dysfunction in rats with diet-induced obesity

Molecular and Cellular Biochemistry volume 476, pages 4019–4029 (2021)Cite this article

Abstract

In the past decade, monoamine oxidase (MAO) with 2 isoforms, MAO-A and B, has emerged as an important source of mitochondrial reactive oxygen species (ROS) in cardio-metabolic pathologies. We have previously reported that MAO-related oxidative stress mediates endothelial dysfunction in rodent models of diabetes and diabetic patients; however, the role of MAO in the vascular impairment associated to obesity has not been investigated so far. Metformin (METF), the first-line drug in the therapy of type 2 diabetes mellitus, has been reported to elicit vasculoprotective effects via partially elucidated mechanisms. The present study was purported to assess the effects of METF on MAO expression, ROS production and vasomotor function of aortas isolated from rats with diet-induced obesity. After 24 weeks of high calorie junk food (HCJF) diet, isolated aortic rings were prepared and treated with METF (10 μM, 12 h incubation). Measurements of MAO expression (quantitative PCR and immune histochemistry), ROS production (spectrometry and immune-fluorescence) and vascular reactivity (myograph studies) were performed in rat aortic rings. MAO expression was upregulated in aortic rings isolated from obese rats together with an increase in ROS production and an impairment of vascular reactivity. METF decreased MAO expression and ROS generation, reduced vascular contractility and improved the endothelium-dependent relaxation in the diseased vascular preparations. In conclusion, METF elicited vascular protective effects via the mitigation of MAO-related oxidative stress in the rat model of diet-induced obesity.

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Acknowledgements

The study was funded by the “Victor Babeș” University of Medicine and Pharmacy Timișoara, RO internal grant nr. 6POSTDOC/2020.

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Authors and Affiliations

  1. Department of Functional Sciences III, Discipline of Pathophysiology, Center for Translational Research and Systems Medicine, “Victor Babeș” University of Medicine and Pharmacy Timişoara, Romania, Eftimie Murgu Sq., no. 2, 300041, Timișoara, Romania

    Loredana N. Ionică, Anca M. Bînă, Danina M. Muntean & Adrian Sturza

  2. Department of Internal Medicine VII, Discipline of Diabetes, Nutrition and Metabolic Diseases, “Victor Babeș” University of Medicine and Pharmacy Timișoara, Romania, Eftimie Murgu Sq., no. 2, 300041, Timișoara, Romania

    Laura Gaiță, Anca M. Bînă & Alexandra Sima

  3. Department of Cardiology VI, 2nd Discipline of Cardiology, “Victor Babeș” University of Medicine and Pharmacy Timișoara, Romania, Eftimie Murgu Sq., no. 2, 300041, Timișoara, Romania

    Raluca Soșdean

  4. Department of Infectious Diseases XIII, Discipline of Parasitology, “Victor Babeș” University of Medicine and Pharmacy Timișoara, Romania, Eftimie Murgu Sq., no. 2, 300041, Timișoara, Romania

    Rodica Lighezan

  5. Department XV, Discipline of Radiology and Medical Imagistics, “Victor Babeș” University of Medicine and Pharmacy Timișoara, Romania, Eftimie Murgu Sq., no. 2, 300041, Timișoara, Romania

    Daniel Malița

  6. Department of Surgery IX, Discipline of Surgical Semiotics 1, Center for Hepato-Biliary and Pancreatic Surgery, “Victor Babeș” University of Medicine and Pharmacy Timișoara, Romania, Eftimie Murgu Sq. no. 2, 300041, Timișoara, Romania

    Octavian M. Crețu & Ovidiu Burlacu

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  1. Loredana N. Ionică
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Ionică, L.N., Gaiță, L., Bînă, A.M. et al. Metformin alleviates monoamine oxidase-related vascular oxidative stress and endothelial dysfunction in rats with diet-induced obesity. Mol Cell Biochem 476, 4019–4029 (2021). https://doi.org/10.1007/s11010-021-04194-2

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Keywords

  • Metformin; monoamine oxidase
  • Obesity
  • Diabetes
  • Rats
  • Oxidative stress
  • Endothelial dysfunction