Advanced Glycation End Products-Mediated Renal Cell Dysfunction Andameliorating Effect of Ramipril And Losartan

INTRODUCTION: Hyperglycemia-mediated advanced glycation end products (AGEs) formation is one of the major factor leading to renal cell injury in diabetic patients. The interaction of AGEs with receptor for advanced glycation end products (RAGE) is believed to induce downstream signaling of various effectors-leading to renal fibrosis in diabetic nephropathy (DN). Angiotensin converting enzyme inhibitor (ramipril) and angiotensin II receptor blocker (losartan) are the antihypertensive drugs known for their reno-protective activity. AIMS AND OBJECTIVES: The present study was designed to explore the effect of advanced glycation end products (AGEs) on renal cell dysfunction by assessing reactive oxygen species (ROS) production and mRNA expression of NADPH oxidase p47phox subunit, TGF [beta]1 and fibronectin in AGE-exposed renal cells along with effect of ramipril and losartan on these parameters. MATERIAL AND METHODS: The cultured human renal proximal tubular epithelial cells (HK-2 cells)were treated with 200 [micro]g/ml of artificially made AGEs using bovine serum albumin (AGE-BSA) and unmodified BSA for 24 h. The HK-2 cells were also co-treated with drugs namely; ramipril (5 [micro]M) and losartan (5 [micro]M). ROS generation was assessed by using 2',7'-dichlorodihydrofluorescein diacetate (H2DCFDA) method. NADPH oxidase p47phox subunit, RAGE, TGF P1 and fibronectin mRNA expression was assessed by using real-time PCR. RESULTS: A significant increased (p