EFFECTS OF TELMISARTAN AND IMIDAPRIL ON HIGH GLUCOSE/ANTIMYCIN A-INDUCED CELL DAMAGE IN HUMAN RENAL PROXIMAL TUBULAR EPITHELIAL CELLS: PP.24.480

Abstract

Objective: It is reported that high glucose induced cytotoxicity, oxidative stress and apoptosis in renal tubular cells. In contrast, renal ischemia/reperfusion injury is a common cause of acute kidney injury. In the present study, we investigated the effect of angiotensin II type 1 (AT1) receptor blocker (ARB) and/or angiotensin converting enzyme inhibitor (ACEI) on high glucose- or antimycin A-induced cell damage in human renal proximal tubular epithelial cells (RPTEC). Design and Method: The N-acetyl-β-D-glucosaminidase (NAG) release and caspase 3/7 activity in RPTEC after high glucose (4x10–2 mol/L) or antimycin A (1x10–5 mol/L) treatment with telmisartan/imidapril were determined using modified commercial procedure. 8-hydroxy-2’-deoxyguanosine (8-OHdG) was also measured by a commercially available kit. In addition, the change of Bcl-2 protein levels in RPTEC were measured using Western blotting after antimycin A treatment with telmisartan/imidapril. Results: High glucose treatment significantly increased NAG release into the medium from RPTEC compared with those in regular glucose medium (1.75x10–2 mol/L). Telmisartan/imidapril (1x10–9–10–7 mol/L) showed a significant reduction on high glucose-induced NAG release in RPTEC. High glucose treatment showed significant increases of 8-OHdG in RPTEC, and telmisartan significantly decreased high glucose-induced 8-OHdG. NAG release and caspase 3/7 activity were significantly increased after antimycin A treatment and telmisartan/imidapril treatment significantly decreased antimycin A-induced NAG release and caspase 3/7 activity. Antimycin A treatment significantly reduced Bcl-2 protein levels and telmisartan/imidapril treatment completely reversed the reduction. No additional effects in combination with telmisartan and imidapril were observed in any treatment in the present study. Conclusions: High glucose or antimycin A treatment increase NAG release, caspase 3/7 activity and decrease Bcl-2 protein levels in RPTEC and telmisartan/imidapril treatment attenuate the effects. The present studies demonstrate that ARB and ACEI are both useful in high glucose- or ischemia/reperfusion-induced renal tubular cell damage, however, using their combination was not superior to telmisartan/imidapril alone.