Investigation of the potential effect of AGEs inhibitors for improvement of diabetics wound healing

Bin Ammar, Albandari (2019) Investigation of the potential effect of AGEs inhibitors for improvement of diabetics wound healing. Doctoral thesis (PhD), Manchester Metropolitan University.

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Abstract

Impaired wound healing is associated with hyperglycaemia in patients suffering from diabetes mellitus. Hyperglycaemia induces protein glycation and the formation of advanced glycation endproducts (AGEs). The accumulation of AGEs in the body leads to structural and functional modifications of tissue proteins. Protein glycation is believed to play an important role in the development of diabetic complications. Thus, inhibition of AGE formation may have a role in the prevention of diabetic complications. This thesis was set out to evaluate the potential effects of compounds with antiglycation activities. The investigated compounds include S-allyl cysteine (SAC), N-acetylcysteine (NAC), as well as the synthesised derivative known as compound A. The extent of glycation in the presence and absence of a number of inhibitors include SAC/NAC and compound A were assessed by several methods including fluorescence, sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE)-silver stain, western blotting and enzyme-linked immunosorbent assays (ELISA). Moreover, this work aimed to evaluate and quantify the potential of human adipose mesenchymal stem cells (hADMSCs) to release these ‘drugs’ as potential therapeutics, and therefore hADMSCs were primed with SAC/NAC, compound A and concentration analysed using high performance liquid chromatography (HPLC). The SAC/NAC and compound A showed protective effects against AGEs formation. These inhibitors reduced the cell migration and tube formation of cultured bovine aortic endothelial cells (BAECs) while conditioned medium from SAC/NAC- and compound A-loaded hADMSCs induced the cell migration and tube formation in BAECs. HADMSCs provide a unique opportunity for developing a novel targeting and drug delivery system, which could effectively deliver therapeutics to specific regions of wounds or other damaged tissues. The results show the potential of hADMSCs as a drug delivery method with potential to improve wound healing. The findings from the in vitro study suggest that dietary supplementation with SAC, NAC, and compound A may offer protection against the damage from cross-linked AGEs and therefore would be a potential therapeutic targeting for the development of diabetic complications.