A Brief Study about HDACs: Novel Pharmacological Target in Diabetic Nephropathy

Abstract

The study's major goal was to determine the exact involvement of HDACs in the pathophysiology of Diabetic Nephropathy and whether targeting individual HDACs could slow the course of Diabetic Nephropathy. HDACs inhibitor benefits and drawbacks, as well as prospective challenges.

HDAC inhibitors have several advantages in Diabetic Nephropathy:-Anti-inflammatory effect, anti-fibrotic effect, TGF-beta 1 decreased, Collagen I reduced, Fibronectin reduced-SMA decreased- cadherin reduced, Reduces fibrogenesis, apoptosis, and DNA damage caused by eNOS, iNOS, and TGF-1, Preserves Klotho, Inhibits  Wnt pathway, Inactivation of EGFR pathway, Increases insulin sensitivity, Decreases insulin resistance, Beta cell proliferation, Decreases apoptosis, Restores nephrin and podocin, Suppress inflammatory protein, Insulin secretion increased and improved glucose control. Prevents endothelial  dysfunction due to Diabetes via activation of Nrf2, Prevents hepatic lipid dysfunction. Decrease diabetic retinopathy, Corrects cardiac metabolic function in Diabetic, Decrease body weight and obesity, Prevents aging, Prevents atherosclerosis, Prevents cardiac autophagy, Decreases TNF\(\alpha\), Decreases MMP, Reduces ER stress and Decreases caspase activation via inhibition of ER Stress pathway. The only drawback is many HDAC inhibitors are reported to have excessive ROS generation. However this is counter balanced with klotho which may be activated by specific inhibition of HDAC thus decreasing oxidative stress.