• Journal of Ginseng Research
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• v.40 no.2
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• pp.196-202
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• 2016

Background: Ginsenoside Rd (GSRd), a main component of the root of Panax ginseng, exhibits anti-inflammation functions and decreases infarct size in many injuries and ischemia diseases such as focal cerebral ischemia. M1 Macrophages are regarded as one of the key inflammatory cells having functions for disease progression. Methods: To investigate the effect of GSRd on renal ischemia/reperfusion injury (IRI) and macrophage functional status, and their regulatory role on mouse polarized macrophages in vitro, GSRd (10-100 mg/kg) and vehicle were applied to mice 30 min before renal IRI modeling. Renal functions were reflected by blood serum creatinine and blood urea nitrogen level and histopathological examination. M1 polarized macrophages infiltration was identified by flow cytometry analysis and immunofluorescence staining with $CD11b^+$, $iNOS^+$/interleukin-12/tumor necrosis factor-${\alpha}$ labeling. For the in vitro study, GSRd ($10-100{\mu}g/mL$) and vehicle were added in the culture medium of M1 macrophages to assess their regulatory function on polarization phenotype. Results: In vivo data showed a protective role of GSRd at 50 mg/kg on Day 3. Serum level of serum creatinine and blood urea nitrogen significantly dropped compared with other groups. Reduced renal tissue damage and M1 macrophage infiltration showed on hematoxylin-eosin staining and flow cytometry and immunofluorescence staining confirmed this improvement. With GSRd administration, in vitro cultured M1 macrophages secreted less inflammatory cytokines such as interleukin-12 and tumor necrosis factor-${\alpha}$. Furthermore, macrophage polarization-related pancake-like morphology gradually changed along with increasing concentration of GSRd in the medium. Conclusion: These findings demonstrate that GSRd possess a protective function against renal ischemia/reperfusion injury via downregulating M1 macrophage polarization.

• Molecular & Cellular Toxicology
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• v.2 no.3
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• pp.185-192
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• 2006

To elucidate the molecular mechanisms associated with early renal injury induced by gentamicin, the most commonly used antibiotics worldwide in the treatment of Gram-negative bacterial infections. We have identified genes differentially expressed at different duration of gentamicin administration. C57BL/6 female mice were treated daily with gentamicin (20 mg/kg, 100 mg/kg, and 200mg/kg) for 7 days and then sacrificed at day 1, 3, and 7 after administration. Standard blood biochemistry and histopathological observation indicative of nephrotoxicity were made. Total RNA was extracted from the kidney for microarray analysis using Affymetrix $GeneChip^{\circledR}$. Five hundred and seventy eight genes were identified as being either up-or down-regulated over 2-fold changes during early renal injury (p<0.05) and were analyzed by hierarchical clustering. The results showed that the genes involved in early immune responses were differentially regulated during early renal injury. Principal component analysis (PCA) confirmed sample separation according to the degree of renal toxicity. In addition, we identified two potential biomarkers that may predict early renal toxicity. This data may contribute to elucidate of the genetic events during early renal injury and to discover the potential biomarkers for nephrotoxicity induced by gentamicin.

• The Korean Journal of Physiology and Pharmacology
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• v.25 no.4
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• pp.321-331
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• 2021

Vancomycin, an antibiotic used occasionally as a last line of treatment for methicillin-resistant Staphylococcus aureus, is reportedly associated with nephrotoxicity. This study aimed at evaluating the protective effects of lutein against vancomycin-induced acute renal injury. Peroxisome proliferator-activated receptor gamma (PPARγ) and its associated role in renoprotection by lutein was also examined. Male BALB/c mice were divided into six treatment groups: control with normal saline, lutein (200 mg/kg), vancomycin (250 mg/kg), vancomycin (500 mg/kg), vancomycin (250 mg/kg) with lutein, and vancomycin (500 mg/kg) with lutein groups; they were euthanized after 7 days of treatment. Thereafter, samples of blood, urine, and kidney tissue of the mice were analyzed, followed by the determination of levels of N-acetyl-β-D-glucosaminidase (NAG) in the urine, renal creatine kinase; protein carbonyl, malondialdehyde, and caspase-3 in the kidney; and the expression of PPARγ, nuclear factor erythroid 2-related factor 2 (Nrf2), and nuclear factor-kappaB (NF-κB) in renal tissue. Results showed that the levels of protein carbonyl and malondialdehyde, and the activity of NAG, creatine kinase and caspase-3, were significantly increased in the vancomycin-treatment groups. Moreover, the levels of Nrf2 significantly decreased, while NF-κB expression increased. Lutein ameliorated these effects, and significantly increased PPARγ expression. Furthermore, it attenuated vancomycin-induced histological alterations such as, tissue necrosis and hypertrophy. Therefore, we conclude that lutein protects against vancomycin-induced renal injury by potentially upregulating PPARγ/Nrf2 expression in the renal tissues, and consequently downregulating the pathways: inflammation by NF-κB and apoptosis by caspase-3.

• Journal of Trauma and Injury
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• v.29 no.4
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• pp.191-194
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• 2016

Pseudo-renal failure presents with renal failure characteristics, such as hypercreatininemia and hyperkalemia without a change in glomerular filtration rate or structure of the kidney. Pseudo-renal failure due to trauma is difficult to diagnose, because symptoms are non-specific and other factors may cause hypercreatininemia and hyperkalemia. In a trauma patient, especially one with pelvic injury, the abrupt elevation of potassium, blood urea nitrogen, and creatinine levels without previous medical history is a key feature in the diagnosis of urinary ascites. We report a case of pseudo-renal failure caused by intraperitoneal bladder rupture in a multiple trauma patient.

• Journal of Trauma and Injury
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• v.37 no.3
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• pp.171-181
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• 2024

Renal injuries commonly occur in association with blunt trauma, especially in the setting of motor vehicle accidents. Contrast-enhanced computed tomography is considered the gold-standard imaging modality to assess patients for renal injuries in the setting of blunt and penetrating trauma, and to help classify injuries based on the American Association for the Surgery of Trauma injury scoring scale. The management of renal trauma has evolved in the past several decades, with a notable shift towards a more conservative, nonoperative approach. Advancements in imaging and interventional radiological techniques have enabled diagnostic angiography with angiographic catheter-directed embolization to become a viable option, making it possible to avoid surgical interventions that pose an increased risk of nephrectomy. This review describes the current management of renal trauma, with an emphasis on renal artery embolization techniques.

• Childhood Kidney Diseases
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• v.23 no.1
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• pp.53-57
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• 2019

Renal cortical necrosis (RCN) is patchy or diffuse ischemic destruction of the renal cortex caused by significantly reduced renal arterial perfusion. It is a rare cause of acute kidney injury (AKI) and is associated with high mortality. Here, we review the case of RCN in a 15-year-old boy who developed AKI. A 15-year-old boy was referred to our hospital from a local hospital due to a sharp decrease in his renal function. He presented with acute flank pain, nausea with vomiting, and oliguria for the past two days. He had taken a single dose of antihistamine for nasal congestion. At our hospital, his peak blood pressure was 148/83 mmHg and he had a high body mass index of $32.9kg/m^2$. The laboratory data showed a blood urea nitrogen (BUN) of 28.4 mg/dL, a creatinine of 4.26 mg/dL, and a glomerular filtration rate estimated from the serum cystatin C of $20.2mL/min/1.73m^2$. Proteinuria (spot urine protein to creatinine ratio 1.66) with pyuria was observed. Kidney sonography showed parenchymal swelling and increased renal echogenicity. Due to rapidly progressing nephritis, steroid pulse therapy (750 mg/IV) was done on the second day of his admission and the patient showed complete recovery with normal renal function. However, the kidney biopsy findings revealed renal cortical hemorrhagic necrosis. Multifocal, relatively well-circumscribed, hemorrhagic necrotic areas (about 25%) were detected in the tubulointerstitium. Although RCN is an unusual cause of AKI, especially in children, pediatricians should consider the possibility of RCN when evaluating patients with rapidly decreasing renal function.

• The Korean Journal of Physiology and Pharmacology
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• v.25 no.5
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• pp.413-423
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• 2021

Apoptosis is proved responsible for renal damage during ischemia/reperfusion. The regulation for renal apoptosis induced by ischemia/reperfusion injury (IRI) has still been unclearly characterized to date. In the present study, we investigated the regulation of histone acetylation on IRI-induced renal apoptosis and the molecular mechanisms in rats with the application of curcumin possessing a variety of biological activities involving inhibition of apoptosis. Sprague-Dawley rats were randomized into four experimental groups (SHAM, IRI, curcumin, SP600125). Results showed that curcumin significantly decreased renal apoptosis and caspase-3/-9 expression and enhanced renal function in IRI rats. Treatment with curcumin in IRI rats also led to the decrease in expression of p300/cyclic AMP response element-binding protein (CBP) and activity of histone acetyltransferases (HATs). Reduced histone H3 lysine 9 (H3K9) acetylation was found near the promoter region of caspase-3/-9 after curcumin treatment. In a similar way, SP600125, an inhibitor of c-Jun N-terminal kinase (JNK), also attenuated renal apoptosis and enhanced renal function in IRI rats. In addition, SP600125 suppressed the binding level of p300/CBP and H3K9 acetylation near the promoter region of caspase-3/-9, and curcumin could inhibit JNK phosphorylation like SP600125. These results indicate that curcumin could attenuate renal IRI via JNK/p300/CBP-mediated anti-apoptosis signaling.

• Herbal Formula Science
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• v.29 no.1
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• pp.33-44
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• 2021

Renal ischemia-reperfusion injury(IRI), an important cause of acute renal failure (ARF), cause increased renal tubular injury. Jesaeng-sinkihwan (JSH) was recorded in a traditional Chines medical book named "Bangyakhappyeon (方藥合編)". JSH has been used for treatment of diabetes and glomerulonephritis with patients. Here we investigate the effects of Jesaeng-sinkihwan (JSH) in a mouse model of ischemic acute kidney injury. The animals model were divided into four groups at the age of 8 weeks; sham group: C57BL6 male mice (n=9), I/R group: C57BL6 male mice with I/R surgery (n=9), JSH Low group: C57BL6 male mice with surgery + JSH 100 mg/kg/day (n=9) and JSH High group: C57BL6 male mice with surgery + JSH 300 mg/kg/day (n=9). Ischemia was induced by clamping the both renal arteries during 25 min, and reperfusion was followed. Mouse were orally given with JSH (100 and 300 mg/kg/day during 3 days after surgery. Treatment with JSH significantly ameliorates creatinine clearance(Ccr), Creatinine (Cr) and blood urea nitrogen(BUN) in obtained plasma. . Treatment with JSH reduced kidney inflammation markers such as Neutrophil Gelatinase Associated Lipocalin (NGAL) and kidney injury molecule-1 (KIM-1). JSH also reduced the periodic acid schiff (PAS) staining intensity and picro sirius red staining intensity in kidney of I/R group. These findings suggest that JSH ameliorates tubular injury including renal dysfunction in I/R induced ARF mouse.

• Korean Journal of Transplantation
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• v.28 no.3
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• pp.135-143
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• 2014

Background: Kidney injury molecule-1 (KIM-1) is known as a good ancillary marker of acute kidney injury (AKI) and its expression has also been observed in acute rejection and chronic graft dysfunction. We tested usefulness of KIM-1 as an indicator of acute and chronic renal graft injury by correlating KIM-1 expression with renal graft function and histology. Methods: A total of 133 zero-time biopsies and 42 follow-up biopsies obtained within 1 year posttransplantation were selected. Renal tubular KIM-1 staining was graded semiquantitatively from 0 to 3 and the extent of staining was expressed as the ratio of KIM-1 positive/CD10 positive proximal tubules using Image J program. Results: KIM-1 was positive in 39.8% of zero-time biopsies. KIM-1 positive cases were predominantly male and had received grafts from donors with older age, deceased donors, and poor renal function at the time of donation, compared with KIM-1 negative cases. KIM-1 expression showed correlation with delayed graft function and acute tubular necrosis. In comparison of KIM-1 expression between stable grafts (n=23) and grafts with dysfunction (n=19) at the time of repeated biopsy, the intensity/extent of KIM-1 staining and renal histology at zero-time did not differ significantly between the two groups. Histologically, KIM-1 expression was significantly increased with both acute and chronic changes of glomeruli, tubules and interstitium, peritubular capillaritis, and arteriolar hyalinosis. Conclusions: KIM-1 can be used as an ancillary marker of AKI and a nonspecific indicator of acute inflammation and tubulointerstitial fibrosis. However, KIM-1 expression at zero-time is not suitable for prediction of long-term graft dysfunction.

• Biomedical Science Letters
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• v.11 no.4
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• pp.441-446
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• 2005

The molecular mechanism of ischemia/reperfusion injury remains unclear. Reactive oxygen species (ROS) are implicated in cell death caused by ischemia/reperfusion in vivo or hypoxia in vitro. Poly (ADP-ribose) polymerase (PARP) activation has been reported to be involved in hydrogen peroxide-induced cell death in renal epithelial cells. This study was therefore undertaken to evaluate the role of P ARP activation in chemical hypoxia in opossum kidney (OK) cells. Chemical hypoxia was induced by incubating cells with antimycin A, an inhibitor of mitochondrial electron transport. Exposure of OK cells to chemical hypoxia resulted in a time-dependent cell death. In OK cells subjected to chemical hypoxia, the generation of ROS was increased, and this increase was prevented by the $H_2O_2$ scavenger catalase. Chemical hypoxia increased P ARP activity and chemical hypoxia-induced cell death was prevented by the inhibitor of PARP activation 3-aminobenzamide. Catalase prevented OK cell death induced by chemical hypoxia. $H_2O_2$ caused PARP activation and $H_2O_2-induced$ cell death was prevented by 3-aminobenzamide. Taken together, these results indicate that chemical hypoxia-induced cell injury is mediated by PARP activation through H202 generation in renal epithelial cells.