The synergistic effect of antiglycating agents (MB-92) on inhibition of protein glycation, misfolding and diabetic complications in diabetic-atherosclerotic rat

Mahdavifard, S and Bathaie, S.Z and Nakhjavani, M and Taghikhani, M (2016) The synergistic effect of antiglycating agents (MB-92) on inhibition of protein glycation, misfolding and diabetic complications in diabetic-atherosclerotic rat. European Journal of Medicinal Chemistry.

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Abstract

Abstract Protein glycation due to hyperglycemia resulting in misfolding and aggregation, which is known as one of the most important reasons of diabetes complications. We previously showed the beneficial effects of some antiglycating agents in diabetic rats. Here, the effect of MB-92, a combination of some amino acids and crocetin (Crt, a saffron carotenoid), was studied in the prevention of diabetic complications in diabetic-atherosclerotic rats. In addition, the inhibitory effect of these treatments on glycation intermediates, aggregation and misfolding of proteins was investigated both in vivo and in vitro. Thus, the streptozotocin-induced diabetic rats that underwent an atherogenic diet were treated with Crt, N-acetylcyctein and MB-92. Then, glycated products and markers of oxidation and inflammation, in addition to other markers of diabetes complications were studied. The results of the in vivo study indicated that the mentioned treatments prevented the atheromatos formation, reduced the increased blood glucose; inhibited the formation of various glycation products, induced glyoxalase system (I and II), diminished oxidation and inflammatory markers, and improved lipid profile and atherosclerotic index in the diabetic-atherosclerotic rats; but MB-92 was the most effective treatment. In vitro results also confirmed that MB-92 was the most effective treatment to inhibit protein glycation and misfolding in comparison with the other treatments. In conclusion, MB-92 showed the greatest potential for inhibition of glycation and oxidation products, atheromatose plaque formation and inflammation in diabetic-atherosclerotic rats, and to control protein glycation, misfolding and aggregation in high glucose concentration; thus, it can be suggested as a new drug to prevent diabetic complications. Keywords: Combinatorial Therapy; Glycated Products; Misfolding; Aggregation; Diabetic Complications; Atheromatose Plaque; Crocetin; Amino Acids and Streptozotocin

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