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Antiglycation study of HMG-R inhibitors and tocotrienol against glycated BSA and LDL: A comparative study

Nabi, Rabia, Alvi, Sahir Sultan, Khan, Rizwan Hasan, Ahmad, Shafeeque, Ahmad, Saheem, Khan, M. Salman
International journal of biological macromolecules 2018 v.116 pp. 983-992
advanced glycation end products, cardiovascular diseases, cholesterol, diabetic complications, enzyme inhibitors, glycation, hydroxymethylfurfural, hydroxymethylglutaryl-CoA reductase (NADH), low density lipoprotein, morbidity, mortality, pathogenesis, patients, pleiotropy, protein secondary structure, therapeutics, tocotrienols
Non-enzymatic glycation mediated advanced glycation end products (AGEs) generation results in the pathogenesis of diabetic complications and atherosclerotic cardiovascular disease (ASCVD) which is greatly influenced by 3-hydroxy-3-methyl-glutaryl Co-A reductase (HMG-R) activity. HMG-R inhibitors, statins, are well known for reducing mortality and morbidity of ASCVD in patients with diabetes due to their pleiotropic effects independent of cholesterol lowering. Due to distinct chemical structures, various statins may play important role in the inhibition of AGEs mediated pathologies. Herein, we evaluated the anti-glycating potential of atorvastatin (AT), rosuvastatin (RT), pitavastatin (PT), fluvastatin (FT), simvastatin (ST) alone as well in combination with ezetimibe (EZ) and tocotrienol (TT) against d-ribose mediated BSA and LDL glycation by various physicochemical approaches. Our data suggested that AT, TT, RT, EZ, EZ-AT, and EZ-RT were able to substantially inhibit the AGEs formation via modulation of hyperchromicity, fluorogenic AGEs, % contribution of α-helix and β-sheets to protein secondary structure, amide-I band stretching, carbonyl and HMF content in Gly-BSA as well as Gly-LDL. On the basis of above findings, we concluded that HMG-R inhibitors and TT, alone or in combination with EZ, may be established as terrific therapeutic agents for the patients suffering from AGEs induced diabetic cum ASCVD complications.