Ameliorative effect of pioglitazone on glucose induced glycation of α-crystallin: Management of complications associated with diabetic retinopathy

The glycation and aggregation of lens proteins significantly contribute to the onset of diabetic cataracts as well as the retinopathy. The glycation exerts numerous alterations in the tertiary structural of proteins. Moreover, the covalent crosslinking of lens crystallins also contribute to the cataract formation. In this article, the effect of pioglitazone on glucose induced glycation and aggregation α-crystallin was examined. A remarkable inhibition of early glycation products (~80%) and advanced glycation products (~75%) was recorded by the treatment of pioglitazone. There was >75% recovery in biochemical marker (carbonyl content). The presence of 150 μM of pioglitazone reduced the free lysine modifications to 35%. Treatment of pioglitazone also protected the secondary structural alterations induced by glycation and inhibited the formation of protein aggregates. The interaction studies showed that pioglitazone interacted with α-crystallin via moderate binding affinity. The interaction between pioglitazone interacted and α-crystallin was energetically and entropically favourable. The complex of pioglitazone with studied protein stable in which RMSF, Rg, SASA, RMSD, and the secondary structural components was not affected. The findings show antiglycation activity of pioglitazone along with its mechanism of action highlighting the ability of drug to be possibly developed novel as glycation inhibitor.