Metformin environmental exposure: A systematic review

Ambrosio‐Albuquerque, Eliane Papa; Cusioli, Luís Fernando; Bergamasco, Rosângela; Gigliolli, Adriana Aparecida Sinópolis; Lupepsa, Luara; Paupitz, Brennda Ribeiro; Barbieri, Pablo Américo; Borin-Carvalho, Luciana Andreia; Portela-Castro, Ana Luiza de Brito

doi:10.1016/j.etap.2021.103588

Cited by 64 publications

(34 citation statements)

References 46 publications

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“…The expanded use of metformin may have an environmental impact as metformin has been widely detected in the aquatic environment of many countries, including the Great Lakes in North America, with concentrations ranging from ng/l to mg/l [471][472][473]. There are no known metabolites of metformin, and it may accumulate and negatively affect numerous organisms as has already reported in species of fish.…”

Section: Discussionmentioning

confidence: 99%

Metformin: Is it a drug for all reasons and diseases?

et al. 2022

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Section: Discussionmentioning

confidence: 99%

Metformin: Is it a drug for all reasons and diseases?

et al. 2022

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“…In the U.S., metformin was the fourth most commonly prescribed medication, and prescriptions rose from 54.5 million in 2006 to 85.7 million in 2019 . Notably, unlike most pharmaceuticals, metformin is not metabolized in the human body by design, and almost all of the intake dose is excreted through urine and feces. , Thus, the widespread use has resulted in the frequent detection of metformin in global aquatic systems since 1999. , The demonstrated adverse effects for aquatic organisms make metformin a major contaminant of emerging concern, as reviewed elsewhere. ,− The environmental occurrence of metformin is attributable to its lack of metabolism in the human body and discharge through municipal wastewater treatment plants (WWTPs), , urban stormwater runoff, final landfill leachates, food process wastewater facilities, on-site septic systems, land application of municipal biosolids, etc. WWTPs cannot completely degrade metformin. , As a result, metformin and the generated transformation byproducts (TPs) are continuously discharged into aquatic systems and spread worldwide. ,, Metformin is also subject to transformation during natural processes and drinking water disinfection. − However, previous reviews mainly summarized the removal efficiency of metformin by different treatment methods but ignored the transformation pathways, TP generation, and whether such transformation would alleviate ecotoxicity.…”

Section: Introductionmentioning

confidence: 99%

“…Four previous reviews on metformin by Briones et al, Tao et al, Elizalde-Velázquez et al, and Ambrosio-Albuquerque et al have been published, and they focused on the global use, distribution, treatment, and toxic effects of metformin but mostly ignored the generation of numerous TPs and the enhanced toxic effects. ,− Only one TP of metformin, GU, was mentioned in these reviews, but the discussion was limited to its occurrence in water and toxicity to organisms. However, 246 more studies have been published in the last six years (2016–2021), 22% of which exclusively focused on the removal of metformin (Figure S1).…”

Section: Introductionmentioning

confidence: 99%

Metformin Contamination in Global Waters: Biotic and Abiotic Transformation, Byproduct Generation and Toxicity, and Evaluation as a Pharmaceutical Indicator

Zhang

2022

Environ. Sci. Technol.

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Metformin is the first-line antidiabetic drug and one of the most prescribed medications worldwide. Because of its ubiquitous occurrence in global waters and demonstrated ecotoxicity, metformin, as with other pharmaceuticals, has become a concerning emerging contaminant. Metformin is subject to transformation, producing numerous problematic transformation byproducts (TPs). The occurrence, removal, and toxicity of metformin have been continually reviewed; yet, a comprehensive analysis of its transformation pathways, byproduct generation, and the associated change in adverse effects is lacking. In this review, we provide a critical overview of the transformation fate of metformin during water treatments and natural processes and compile the 32 organic TPs generated from biotic and abiotic pathways. These TPs occur in aquatic systems worldwide along with metformin. Enhanced toxicity of several TPs compared to metformin has been demonstrated through organism tests and necessitates the development of complete mineralization techniques for metformin and more attention on TP monitoring. We also assess the potential of metformin to indicate overall contamination of pharmaceuticals in aquatic environments, and compared to the previously acknowledged ones, metformin is found to be a more robust or comparable indicator of such overall pharmaceutical contamination. In addition, we provide insightful avenues for future research on metformin.

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“…It is widely used all over the world because of its efficacy, low cost, weight neutrality, and good safety profile [ 2 ]. However, metformin has become one of the most common pharmaceuticals found in wastewater and river basins all over the world with the increasing prescription and consumption [ 3 ]. Studies showed that metformin has some certain toxicity to aquatic organisms.…”

Section: Introductionmentioning

confidence: 99%

Genotoxicity Evaluation of Metformin in Freshwater Planarian Dugesia japonica by the Comet Assay and RAPD Analysis

Yin

Feng

et al. 2022

BioMed Research International

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Objective. To investigate the genotoxicity of metformin on planarian with different concentrations and exposure times. Methods. The planarians were treated, respectively, with 10 mmol/L and 50 mmol/L metformin for 1, 3, and 5 days, and then, the comet assay and random amplified polymorphic DNA (RAPD) analysis were performed. 13 random primers were used for PCR amplification with the genomic DNAs as templates. Planarians cultured in clear water were used as the control. Genomic template stability (GTS) was calculated by comparing and analyzing the RAPD patterns of the control group and the treatment groups. Results. In the comet assay, DNA damage of planarians treated with 10 mmol/L metformin for 1, 3, and 5 days was 10.2%, 25.4%, and 36.8%, respectively, and that of planarians treated with 50 mmol/L metformin was 40.6%, 62.8%, and 65.4%, respectively. GTS values of planarians exposed to 10 mmol/L metformin for 1, 3, and 5 days were 64.1%, 62.8%, and 52.6%, respectively, and those of planarians exposed to 50 mmol/L metformin for 1, 3, and 5 days were 52.6%, 51.3%, and 50%, respectively. DNA damage increased and GTS values decreased with the increasing metformin exposure concentration and exposure time. Conclusion. Metformin has certain genotoxicity on planarian in a dose- and time-related manner. The comet assay and RAPD analysis are highly sensitive methods for detecting genotoxicity with drugs.

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Metformin environmental exposure: A systematic review

Cited by 64 publications

References 46 publications

Metformin: Is it a drug for all reasons and diseases?

Metformin: Is it a drug for all reasons and diseases?

Metformin Contamination in Global Waters: Biotic and Abiotic Transformation, Byproduct Generation and Toxicity, and Evaluation as a Pharmaceutical Indicator

Genotoxicity Evaluation of Metformin in Freshwater Planarian Dugesia japonica by the Comet Assay and RAPD Analysis

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