Accumulation of advanced glycation end products (AGEs) in diabetes leads to progressive neurodegeneration and development of end-stage renal disease. In chronic hyperglycemia enormous amounts of reactive oxygen species (ROS) are generated and highly reactive molecules such as methylglyoxal (MGO), glyoxal (GO) and 3-deoxyglucosone (3-DG) formed from glucose in the cells cause microvascular and macrovascular complications in diabetes. They affect secretion of insulin from pancreatic β-cells as well. Recently we studied binding and modification of proteins (HAS-MGO, BSA-MGO, RNAs-MGO) and reported the efficacy of Okra Seed phytochemicals in inhibiting AGEs. Inhibitory effects of OSE were comparable with the well-established antidiabetic drugs, metformin and aminoguanidine as revealed by AGEs-associated absorbance changes, SDS-gels and fluorescence emission profiles. Unusual changes in the absorbance of AGEs and fluorescence data of modified proteins tempted us to study in detail the mass spectral characteristics of MGO-Metformin, MGO-Aminoguanidine and OSE-MGO adducts followed by UV-visible NanoDrop spectrometry and analytical TLC. ESI-MS: MGO-Met Adduct showed M/Z 184 (100%) [Triazepinone], its condensation product M/Z 202, its dehydration product M/Z 184 as triazepinone. Higher mass range peaks provided M/Z 256 (40%) , M/Z 274 (22%) (the peak (274-18) =256. This signifies the addition of another mole of MGO to triazepinone. Peak at M/Z 114 ( is attributed to loss of carbon monoxide (CO) from the triazepinone molecule. ESI-MS: [MGO-Aminoguanidine(AG) Adduct] M/Z 111 (100%), M/Z 129 (15%) and (129-H2O)= 111. Similarly reaction of MGO (1.4 equivalent) with OSE was performed with the Phosphate buffer at PH 7.2 analyzed and reaction monitored via UV-visible NanoDrop Spectrometry and TLC. The typical fragmentation mass spectral data of different metabolites generated in these studies show that the further reaction of MGO with triazepinone (M/Z 256) is a mechanism for the excretion of toxic metabolites methylglyoxal and glyoxal which get excreted in urine of diabetic patients suffering from end-stage renal disease. The reaction of these adducts with N-acetyl cysteine, a very powerful antioxidant will also be discussed.

Chemistry and mass spectral characterization of methylglyoxal adducts formed with metformin, aminoguanidine and okra seed extract: Relevance to diabetic complications

251st National Meeting (2016)

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