3-Aminobenzamide, a Poly ADP Ribose Polymerase Inhibitor, Attenuates Renal Ischemia/Reperfusion Injury

Abstract

Introduction. This study was designed to investigate whether 3-amino benzamide (3-AB), a poly (ADP-ribose) polymerase (PARP) inhibitor, has a protective effect on kidney injury induced by renal ischemia/reperfusion (I/R) by decreasing oxidative and nitrosative stress on renal dysfunction and injury. Materials and Methods. Thirty-two male SpragueDawley rats were divided into four groups: sham-operated, sham-operated + 3-AB, I/R, I/R + 3-AB. Rats were given 3-AB (100 mg/kg/day ip) 14 days prior to I/R. I/R and I/R + 3-AB groups underwent 60 min of bilateral renal ischemia followed by 6 h of reperfusion. After reperfusion, kidneys and blood were obtained for evaluation. Superoxide dismutase, glutathione peroxidase, malondialdehide, protein carbonyl content, and nitrite/nitrate level (NO x ) were determined in the renal tissue. Serum creatinine (S Cr ), blood urea nitrogen (BUN), and aspartate aminotransferase (AST) were determined in the blood. Additionally, renal sections were used for histological grade of renal injury. Results. 3-AB significantly reduced the I/R-induced increases in S Cr , BUN, and AST. In addition, 3-AB markedly reduced elevated oxidative stress product, restored decreased antioxidant enzymes, and attenuated histological alterations. Moreover, 3-AB attenuated the tissue NO x levels, indicating reduced NO production. Conclusions. 3-AB has beneficial effect on renal glomerular and tubular dysfunction in rats' kidneys subjected to I/R injury. Moreover, 3-AB has ameliorating effect on both oxidative stress and nitrosative stress of the kidneys, which correlated with histopathological evaluation.

Efficacy of poly(adenosine diphosphate-ribose) polymerase inhibition in extracorporeal shock wave-induced renal injury

“…[37][38][39] In our team's previous works, beneficial effects of PARP inhibition were shown in different experimental inflammatory models. [40][41][42] Therefore, it is possible that treatment with a PARP inhibitor may also attenuate renal injury in kidneys subjected to ESW.…”

Comparison of the Efficacy of Melatonin and 1400W on Renal Ischemia/Reperfusion Injury: A Role for Inhibiting iNOS

“…The production of ONOO − (nitrosative stress) occurs almost instantaneously and causes the nitration of cellular proteins with subsequent loss of protein structure and function. [15,39,40] Therefore, we conclude that ONOO − is critical in renal I/R injury, and that the reduction of ONOO − may be a potential mechanism to prevent kidneys.…”

“…Efficacy of treatment was assessed by tissue level of malondialdehyde (MDA) using the method of Ohkawa et al, protein carbonyl content (PCC) using the method of Levine et al, superoxide dismutase (SOD) using the method of Sun et al, and glutathione peroxidase (GPx) using the method of Paglia and Valentine. [13,30,40] Nitrate and nitrite (NO x ) levels, end products of nitric oxide degradation, were measured using the method described by Miranda et al, as we described in our previous works. [13,30] …”

Beneficial Effects ofN-Acetylcysteine and Ebselen on Renal Ischemia/Reperfusion Injury

“…[18][19][20] On the other hand, some studies have shown the ameliorative effects of therapeutic agents via preventing ROS production, inhibiting enzymes responsible for ROS generation, and administration of antioxidant enzymes and scavenging of ROS. [2][3][4][5][10][11][12]21 In this study, we evaluated the possible beneficial effects of NAC as a free radical scavenger antioxidant. We found that administration of NAC prior to injury showed considerable improvement in renal IRI by decreasing lipid peroxidation and increasing antioxidant enzyme activity.…”

“…16,31 NO and ONOO -are eventually converted to nitrite and/or nitrate. NO x has been used as an indirect but reliable indicator for NO 4,5,21 and ONOO -formation in vivo. 4,36 Therefore, the reduction of ONOO -level and increase in the scavenging of ROS activity may be a potential mechanism to protect kidneys against IRI.…”