A Novel Antioxidant Protects Against Contrast Medium-Induced Acute Kidney Injury in Rats

Abstract

Many studies proposed that oxidative stress and apoptosis are key mechanisms in the pathogenesis of contrast-induced acute kidney injury (CI-AKI). Xylose-pyrogallol conjugate (XP) is an original effective antioxidant that showed decent antioxidant and anti-apoptosis effect before. Thus the therapeutic effect and mechanism of XP in preventing CI-AKI in the short and long term were investigated in this research. Renal function and histological grade were evaluated to determine the severity of renal injury. Kidney samples were then collected for the measurement of oxidative stress markers and the detection of apoptosis. Transmission electron microscopy (TEM) and western blot of mitochondrial protein were utilized for the analysis of the mitochondrial conditions. The results demonstrated that the CI-AKI rats caused a significant decrease in renal function accompanied by a remarkable increase in Malondialdehyde (MDA), bax, caspase-3, cytochrome c (Cyt C) level, TdT-mediated dUTP nick end labeling (TUNEL) positive apoptotic cells, and damaged mitochondria, while a decline in antioxidase activities and mitochondrial superoxide dismutase 2 (SOD2) expression compared with the control rats. However, when XP (50 or 100 or 200 mg/kg/day) was given orally for consecutive 7 days before CI-AKI modeling, XP (200 mg/kg) showed a better capability to restore renal dysfunction, histopathological appearance, the level of apoptosis, mitochondrial damage, oxidative stress, and fibrosis generation without interference in computed tomographic imaging. Our study indicated that antioxidant XP played a nephroprotective role probably via antiapoptotic and antioxidant mechanisms. Besides, XP may regulate the mitochondria pathway via decreasing the ratio of bax/bcl-2, inhibiting caspase-3 expression, cytochrome c release, and superoxide dismutase 2 activity. Overall, XP as a high-efficient antioxidant may have the potentials to prevent CI-AKI.

Metabolomic Study on Iohexol-Induced Nephrotoxicity in Rats Based on NMR and LC–MS Analyses

“…The rats were randomly divided into a control group (control, n = 7) and a CI-AKI group (CI-AKI, n = 7). In this experiment, AKI is established as described in our previous study: 14 rats in the CI-AKI group were injected with iohexol (at a dose of 3 g I/kg) 15 min after the subcutaneous injection of indomethacin and L-NAME (at a dose of 10 mg/kg), while the rats in the control group were injected with the same amount of normal saline.…”

“…14 Scores were assigned according to the percentage of tissue in the corticomedullary region exhibiting renal tubulointerstitial injury per 10 high-power fields as follows: 0 = 0%, 1 < 10%, 2 < 25%, 3 < 50%, and 4 > 50%, as previously described. 14 Metabolomic Analysis Based on UHPLC/Q-Orbitrap-MS. Plasma, urine, and kidney samples were thawed at room temperature.…”

“…The tissue sections of each group were scanned by a microscopic scanner (NanoZoomer S360, Japan), and fields were randomly selected and analyzed semiquantitatively. The detailed process was the same as that of our previous study . Scores were assigned according to the percentage of tissue in the corticomedullary region exhibiting renal tubulointerstitial injury per 10 high-power fields as follows: 0 = 0%, 1 < 10%, 2 < 25%, 3 < 50%, and 4 > 50%, as previously described …”

A Rheostat of Ceramide and Sphingosine-1-Phosphate as a Determinant of Oxidative Stress-Mediated Kidney Injury

“…In contrast, antioxidants restored MRCC [ 153 ], prevented the loss of mitochondrial membrane potential (MMP) [ 148 , 154 , 155 ] and increased the expression of VDAC [ 148 , 154 ] and Bcl-2/Bax ratio [ 63 , 88 , 148 , 156 ], as well as preventing an increase in intracellular Ca 2+ which induces loss of MMP [ 155 ], thereby ameliorating apoptosis in oxidant-induced kidney injury. In fact, antioxidants prevented a cadmium-induced increase in intracellular Ca 2+ [ 155 ] and increased Bcl-2 expression, which prevents a rise in intracellular Ca 2+ [ 156 ], thereby ameliorating apoptosis. These data suggest that mitochondria regulate a rheostat of ROS and antioxidants and vice versa in oxidant-induced kidney injury.…”

Kidney Microcirculation as a Target for Innovative Therapies in AKI

“…Xylose–pyrogallol conjugate is an antioxidant that has recently shown potential for preventing contrast-induced AKI in rats [ 150 ]. In a meta-analysis of 10 randomized controlled trials, a prophylactic treatment with NAC in intravenous NaHCO 3 - reduced contrast-induced AKI by 35% [ 151 ].…”