Ameliorative Effects of Proanthocyanidin on Renal Ischemia/Reperfusion Injury

Abstract

NTRODUCTION Several natural products have been reported to have beneficial effects on ischemia/reperfusion (I/R) injury, particularly from a preventative perspective. Therefore, this study was designed to investigate the efficiency of proanthocyanidin (PA), a natural product derived from grape seed, on renal dysfunction and injury induced by I/R of rat kidney. MATERIALS AND METHODS Twenty‐four male Sprague‐Dawley rats were divided into three groups: sham‐operated, I/R, I/R+PA. Rats were given PA (100 mg/kg/day peroral) 7 days prior to I/R. All rats except sham‐operated 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, malondialdehyde, 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 PA significantly reduced the I/R‐induced increases in S(Cr), BUN, and AST. In addition, PA markedly reduced elevated oxidative stress product, restored decreased antioxidant enzymes, and attenuated histological alterations. Moreover, PA attenuated the tissue NO(x), levels indicating reduced NO production. CONCLUSIONS The pretreatment of rats with PA reduced the renal dysfunction and morphological changes, ameliorated cellular injury, and restored renal antioxidant enzymes caused by renal I/R.

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

“…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] …”

“…[7,15] Various in vivo studies have shown that NO biosynthesis and its action are closely related to the pathogenesis of renal I/R injury. In addition, it has been shown that selective or non-selective iNOS inhibitors prevent I/R injury in skeletal muscle, myocardial infarction, brain, liver, and kidney tissues, [13,[16][17][18][19][20][21] and that iNOS-knockout mice show reduced I/R injury in the kidney. [20] Melatonin is mainly secreted from pineal gland and a variety of non-pineal tissues and organs, including the kidney.…”

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

“…Nitrate plus 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. [5,6] …”

“…[7] In our previous studies, we have shown that the inhibition of iNOS and scavenging of ONOO − reduced the damage in the kidneys subjected to renal I/R. [5,6] Studies have shown that ONOO ® induces cellular injury by activation of poly (ADP-ribose) polymerase (PARP) through damaging DNA. Deoxyribonucleic acid damage is repaired via the activity of several DNA repair enzymes, including PARP enzymes.…”

“…On the other hand, excessive NO production reacts with superoxide ions released from inflammatory cells, producing the potent oxidant peroxynitrite (ONOO − ) and protein tyrosine nitration. [5,6] It has been shown that NO and ONOO − contribute to the evolution of several renal diseases, including immune-mediated glomerulonephritis, obstructive nephropathy, renal I/R injury, and acute and chronic renal allograft rejection. [7] In our previous studies, we have shown that the inhibition of iNOS and scavenging of ONOO − reduced the damage in the kidneys subjected to renal I/R.…”