Potential Therapeutic Effects of Ursodeoxycholic Acid in Comparison to Ramipril in a Rat model of Diabetic Nephropathy

Abstract

Diabetic nephropathy (DN) is a chronic progressive disorder that complicates a long standing diabetes mellitus characterized clinically by microalbuminuria followed by macroalbuminuria, increased blood pressure, and a decline in renal function, which ultimately leads to end-stage renal disease. Albuminuria is a prominent clinical feature of DN and is considered an independent risk factor for disease progression in DN that is linked to alteration of the selective properties of glomerular filtration barrier. Podocyte apoptosis is a major determinant of the development and progression of proteinuria and DN. Endoplasmic reticulum stress (ER stress) evolves in the presence of chronic conditions such as diabetes and is characterized by accumulation of unfolded proteins in the ER resulting in an adaptive cellular response referred to as the unfolded protein response (UPR). When the UPR is consistently activated, three main UPR pathways are augmented to slow the pace of protein translation evolving eventually into a cytotoxic process that promotes apoptosis. Activating transcription factor 6 (ATF6) is an ER-localized protein and a member of UPR pathways that is considered as a major transducing signal linked to