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Antiglycation and cell protective actions of metformin and glipizide in erythrocytes and monocytes

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Abstract

Chronic hyperglycaemia causes glycation which subsequently results in the long-term complications of diabetes. Albumin, the major plasma protein is more sensitive to glycation resulting in structural, biological and physiological modifications. The long-term benefits of commonly used anti-diabetic drugs such as metformin and glipizide in diabetic patients are well understood. However, no extensive study has been performed to assess their role in the glycation induced albumin modifications and cellular protection. We carried out the glycation of bovine serum albumin using methylglyoxal as a glycating agent in absence or presence of metformin and glipizide to establish their anti-glycation action. Different glycation markers (fructosamine, carbonyl groups, free thiol groups and β-amyloid aggregation) and protein structural markers (absorption spectroscopy and native-polyacrylamide gel electrophoresis) were examined. Further THP-1 cells (monocytes) and erythrocytes were treated with drugs that were exposed to glycated albumin samples for 24 h, respectively at 37 °C to investigate the cytoprotective actions of drugs against glycation. After the treatment different anti-oxidant indices (catalase, glutathione, superoxide dismutase and nitric oxide), cell viability, lipid peroxidation and erythrocyte hemolysis were determined. Treatment with metformin and glipizide during in vitro albumin glycation significantly reduced the formation of glycation adducts and inhibited structural modifications. They restored the level of antioxidants in THP-1 and erythrocytes cells treated with glycated albumin thus protecting cells. Our results suggested protection mode of albumin glycation through inhibition by metformin and glipizide. Additionally, they exerted inhibitory actions on glycation-induced cellular damage by restoring cellular antioxidant defense.

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Acknowledgments

We greatly acknowledge all the participants who volunteered in this study and NCCS for providing cell line.

Funding

This study was funded by Department of Biotechnology (DBT) (Grant No: BT/Bio-CARe/08/837/2010-11).

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  1. Biochemical Sciences Division, Rajiv Gandhi Institute of IT and Biotechnology, Bharati Vidyapeeth University, Pune, 411046, Maharashtra, India

    Krishna Adeshara & Rashmi Tupe

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  1. Krishna Adeshara
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Correspondence to Rashmi Tupe.

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Adeshara, K., Tupe, R. Antiglycation and cell protective actions of metformin and glipizide in erythrocytes and monocytes. Mol Biol Rep 43, 195–205 (2016). https://doi.org/10.1007/s11033-016-3947-5

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