Study of the Effects of Complexation of Lead with Metformin, Glimepiride, Vildagliptin and Dapagliflozin in Mice Model and Its Biological Implications

Fahima; Md. Zakir; Mohammad

doi:10.25163/microbbioacts.31210910822111120

Microbial Bioactives

Microbial Bioactives | Online ISSN 2209-2161

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Volume 3 Number 1 2020

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Study of the Effects of Complexation of Lead with Metformin, Glimepiride, Vildagliptin and Dapagliflozin in Mice Model and Its Biological Implications

Fahima Aktar, Md. Zakir Sultan, Mohammad A. Rashid

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Microbial Bioactives 3 (1) 125-133 https://doi.org/10.25163/microbbioacts.31210910822111120

Submitted: 08 October 2020 Revised: 22 October 2020 Published: 11 November 2020

Abstract

Background: Lead is a widespread environmental pollutant present in air, water, and soil, and its persistence in biologically active systems raises important concerns regarding human health, ecological stability, and chemical interactions with therapeutic agents. In contaminated environments, heavy metals may alter the physicochemical behavior and biological performance of pharmaceutical compounds, potentially influencing their efficacy and toxicity. Because such interactions are also relevant to microbiologically active food, water, and environmental systems, understanding lead–drug complex formation is of considerable applied significance. The present study investigated the formation of lead complexes with selected antidiabetic drugs and evaluated their biological consequences in vivo.

Methods: Four antidiabetic drugs—metformin, glimepiride, vildagliptin, and dapagliflozin—were reacted with metallic lead under different conditions to generate four complexes: Pb-metformin, Pb-glimepiride, Pb-vildagliptin, and Pb-dapagliflozin. Complex formation was confirmed by thin-layer chromatography (TLC), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), and Fourier-transform infrared spectroscopy (FT-IR). The physiological effects of the synthesized complexes were then assessed in a mice model by measuring blood glucose, serum creatinine, and uric acid levels, followed by histopathological examination of liver and kidney tissues.

Results: Compared with their parent drugs, the lead-associated complexes showed markedly reduced glucose-lowering efficacy and significantly altered physiological responses. While metformin, glimepiride, vildagliptin, and dapagliflozin reduced blood glucose from 31.54 to 19.02 mmol/L, 30.24 to 17.20 mmol/L, 31.50 to 19.70 mmol/L, and 30.37 to 17.60 mmol/L, respectively, their corresponding lead complexes resulted in substantially weaker glycemic control after 14 days. Serum creatinine and uric acid levels were consistently elevated in mice treated with the lead-associated drug complexes compared with the parent drugs, indicating renal dysfunction and systemic toxicity. Histopathological findings further supported the presence of hepatic and nephrotoxic alterations following treatment with the lead-complex forms.

Conclusion: This study demonstrates that lead contamination can substantially alter the therapeutic behavior and toxicological profile of antidiabetic drugs through complex formation. These findings have broader relevance to environmentally exposed and microbiologically active systems, where pharmaceutical compounds and heavy metals may coexist and interact. The results highlight the need to further investigate heavy metal–drug interactions as an important but often overlooked factor in applied microbiology, environmental health, and biological risk assessment.

Keywords: Lead contamination; Antidiabetic drugs; Heavy metal complexation; Applied microbiology; Environmental toxicity; Creatinine; Uric acid; Biological risk

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Study of the Effects of Complexation of Lead with Metformin, Glimepiride, Vildagliptin and Dapagliflozin in Mice Model and Its Biological Implications

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