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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.
Highlights
Contrast-induced acute kidney injury (CI-AKI) is caused by iodinated contrast media for diagnostic imaging (Azzalini et al, 2016) and it is the third most common reason of hospital-obtained AKI, occurring in more than 30% of patients receiving iodinated contrast media injection, and it is related to a high risk of mortality caused by renal dysfunction (Fahling et al, 2017)
Compared with the Ctrl, contrast medium (CM) injection markedly decreased the activities of superoxide dismutase (SOD) (p < 0.05, Figure 7B), GSH-Px (p < 0.01, Figure 7C) and CAT (p < 0.05, Figure 7D) in renal, and Xylose-pyrogallol conjugate (XP) pretreatment could significantly up-regulate the level of SOD (p < 0.01, Figure 7B), GSH-Px (p < 0.01, Figure 7C), and CAT (p < 0.05, Figure 7D) in renal tissues compared with the CI-AKI group
CI-AKI is one of the main causes of hospital-acquired AKI (Takahashi et al, 2017), and it is generally acknowledged as animal model to explore the efficiency of protective agents
Summary
Contrast-induced acute kidney injury (CI-AKI) is caused by iodinated contrast media for diagnostic imaging (Azzalini et al, 2016) and it is the third most common reason of hospital-obtained AKI, occurring in more than 30% of patients receiving iodinated contrast media injection, and it is related to a high risk of mortality caused by renal dysfunction (Fahling et al, 2017). CI-AKI occurs within 24–72 h following the radiocontrast agents administration and it is correlated to adverse outcomes including acute renal failure requiring dialysis and worsening of CKD (Khwaja, 2012). The major mechanism of CI-AKI may be associate with direct cytotoxic induced apoptosis effects on renal tubular, mitochondrial dysfunction, and oxidative stress (Khwaja, 2012). Numerous preclinical researches showed that protective agents with antioxidant activity could prevent the occurrence of CI-AKI by reducing tubular epithelial cells apoptosis, mitochondrial reactive oxygen species (ROS) production, DNA oxidative damage in kidney tissues (Dennis and Witting, 2017). A probable treatment strategy may include the use of drugs targeting the regulators of apoptosis, mitochondria and renal oxidative stress
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