Abstract

Lead is abundant in the air, water and soil as a pollutant. It is sometimes consumed by humans in excessive amounts, which can lead to toxicity in the body or may interact with soluble drugs, thus altering their therapeutic efficacy. In this study, four antidiabetic drugs were synthesized to form a complex with metallic lead at different conditions. The formation of four complexes viz. Pb-metformin, Pb-glimepiride, Pb-vildagliptin, and Pb-dapagliflozin was established and confirmed by TLC, DSC, TGA and FT-IR data analysis. The physiological effects of these complexes was then examined using a mice model. After treatment, blood glucose, serum creatinine and uric acid were measured and histopathology of hepatic and nephrotic tissues were studied. Control treatments of metformin, glimepiride, vildagliptin and dapagliflozin reduced blood glucose levels in mice 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, whereas Pb-met, Pb-glim, Pb-vilda, and Pb-dapa slightly increased blood glucose levels compared to control after 14 days of treatment from 30.60 to 25.82 mmol/L, 30.22 to 29.23 mmol/L, 31.93 to 25.32 mmol/L and 32.25 to 29.32 mmol/L, respectively. The serum creatinine levels increased from 3.38, 3.96, 3.60 and 3.42 mg/dL on metformin, glimepiride, vildagliptin and dagagliflozin respectively to 4.57, 5.36, 5.21 and 5.24 mg/dL on the lead-complex forms of those respective medications. Similarly, the serum acid levels also increased from 42.91, 44.83, 40.21 and 41.49 mg/dL on metformin, glimepiride, vildagliptin and dagagliflozin respectively to 53.13, 57.40, 49.36 and 53.32 mg/dL on the lead-complex forms of those respective medications. Both high creatinine and uric acid level after treatment with lead complexes indicated nephrotic toxicity.

Keywords: Antidiabetic drugs, complexation, Lead, Creatinine, Uric acid