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Metformin as a protective agent against natural or chemical toxicities: a comprehensive review on drug repositioning

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Abstract

Background

Metformin is the first prescribed drug for hyperglycemia in type 2 diabetes mellitus. Mainly by activating AMPK pathway, this drug exerts various functions that among them protective effects are of the interest.

Purpose

Herein, we aimed to gather data about the protective impacts of metformin against various natural or chemical toxicities.

Results

An extensive search among PubMed, Scopus, and Google Scholar was conducted by keywords related to protection, toxicity, natural and chemical toxins and, metformin. Our literature review showed metformin alongside its anti-hyperglycemic effect has a wide range of anti-toxic effects against anti-tumour and routine drugs, natural and chemical toxins, herbicides and, heavy metals.

Conclusion

It is evident that metformin is a potent drug against the toxicity of a broad spectrum of natural, chemical toxic agents which is proved by a vast number of studies. Metformin mainly through AMPK axis can protect different organs against toxicities. Moreover, metformin preserves DNA integrity and can be an option for adjuvant therapy to ameliorate side effect of other therapeutics.

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Abbreviations

DXR:

Doxorubicin

SOD:

Superoxide dismutase

GSHPx:

Glutathione peroxidase

CAT:

Catalase

MDA:

Malondialdehyde

AST:

Aspartate aminotransferase

ALT:

Alanine transaminase

CK-MB:

Creatinine phosphokinase

GSH:

Glutathione

LDH:

Lactate dehydrogenase

ROS:

Reactive oxygen species

CNP:

Serum C-type natriuretic peptide

TAC:

Total antioxidant capacity

LH:

Luteinizing hormone

FSH:

Follicle-stimulating hormone

NOS:

Nitrite oxide synthase

PCE:

Polychromatic erythrocytes

NCE:

Normochromatic erythrocytes

BALF:

Bronchoalveolar lavage fluid

NADH:

Nicotinamide adenine dinucleotide

AGEs:

Advanced glycation endproducts

AMPK:

AMP-activated protein kinase

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  1. S. E. Meshkani and D. Mahdian contributed equally to this work.

Authors and Affiliations

  1. Cellular and Molecular Research Center, Sabzevar University of Medical Sciences, Sabzevar, Iran

    S. E. Meshkani, D. Mahdian, K. Abbaszadeh-Goudarzi, M. Abroudi & G. Dadashizadeh

  2. Department of Pharmacology, School of Medicine, Sabzevar University of Medical Sciences, Sabzevar, Iran

    D. Mahdian

  3. Department of Biochemistry, School of Medicine, Sabzevar University of Medical Sciences, Sabzevar, Iran

    K. Abbaszadeh-Goudarzi

  4. Pharmaceutical Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran

    H. Hosseinzadeh

  5. Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran

    H. Hosseinzadeh

  6. Department of Endocrinology, Université de Picardie Jules Verne, Amiens, France

    J.-D. Lalau

  7. Department of Biomedical Sciences, Universiteit Antwerpen, Antwerp, Belgium

    M. E. De Broe

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Meshkani, S.E., Mahdian, D., Abbaszadeh-Goudarzi, K. et al. Metformin as a protective agent against natural or chemical toxicities: a comprehensive review on drug repositioning. J Endocrinol Invest 43, 1–19 (2020). https://doi.org/10.1007/s40618-019-01060-3

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