• The Korean Journal of Physiology and Pharmacology
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• 제25권4호
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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.

• Childhood Kidney Diseases
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• 제3권2호
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• pp.109-116
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• 1999

목적 : Insuln-like growth factor(IGF)-I및 -II는 성장인자로 일군의 IGF-binding protein(IGFBP)에 의하여 그 작용이 조절된다. IGF-I은 백서 신장에서 발견되고 대사효과와 성장효과를 갖고 있다. 이번 연구는 백서에서 신장발육과 허혈성 신손상 후 재생과정 동안에 IGFBP의 발현이 변화하는지를 보고자 한다. 방법 : 태생 15주부터 성숙 할때까지 백서 신장에서 IGFBP 발현의 변화를 알아보기 위해 Northern blotting을 시행하였고, 급성신부전 백서의 신장에서 IGF-IGBP axis의 변화를 보기 위해 Northern blotting과 Immunohisto-chemistry를 이용하였다. 결과 : IGFBP-1과 -3는 태생기에는 거의 발현되지 않다가 출생 후 7일째부터 성숙이 끝날 때까지 점진적으로 증가하였다. 반면에 IGFBP-2와 -5는 태생기에 많이 발현되고, IGFBP-2는 출생 후 7일째까지 IGFBP-5는 30일째까지 높은 농도를 유지하다가 급격히 감소하였다. 한편 IGFBP-4는 태생기에 중등도로 발현되는데 출생 후 증가하기 시작하여 7일째 가장 많이 발현되다가 급격히 감소하였다. 신손상 후 IGFBP의 변화를 보면 IGFBP-1과 -4는 재생기간 동안 3-5배 증가되다가 정상으로 회복된 반면 IGFBP-3와 IGFBP Related Protein-1(IGFBPrP-1) 은 신손상 1일째에는 약간 감소하다가 그후 증가하여 정상보다 약간 높은 수준을 유지하였다. 결론 : 백서 신장에서 신장구조나 기능의 발달, 분화 및 재생에 대한 IGF의 작용을 조절할 수 있는 IGFBP 발현에 현저한 변화가 있었다.

• Molecules and Cells
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• 제38권4호
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• pp.285-296
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• 2015

Oxidative stress has been linked to the pathogenesis of diabetic nephropathy, the complication of diabetes in the kidney. NADPH oxidases of the Nox family, and in particular the homologue Nox4, are a major source of reactive oxygen species in the diabetic kidney and are critical mediators of redox signaling in glomerular and tubulointerstitial cells exposed to the diabetic milieu. Here, we present an overview of the current knowledge related to the understanding of the role of Nox enzymes in the processes that control mesangial cell, podocyte and tubulointerstitial cell injury induced by hyperglycemia and other predominant factors enhanced in the diabetic milieu, including the renin-angiotensin system and transforming growth factor-${\beta}$. The nature of the upstream modulators of Nox enzymes as well as the downstream targets of the Nox NADPH oxidases implicated in the propagation of the redox processes that alter renal biology in diabetes will be highlighted.

• 생명과학회지
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• 제9권3호
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• pp.300-307
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• 1999

The enzyme activities and antioxidative of tocopherol and ascorbate were investigated at the levels of liver, kidney homogenates and sera of SD-rats intoxicated with tetrachlorocarbon$CCl_4$. GOT and GPT activities of sera in the $CCl_4$ group were 3, 6 times increased compared to normal group. But they tended to decrease significantly in tocopherol and ascorbate administered group. As for BUN and total cholesterol they were the same. HDL-cholesterol in the $CCl_4$group was 42% decreased compared to normal group. HDL-cholesterol was about 26% increased in the tocopherol group and tocopherol ascorbate group compared to $CCl_4$ group. MDA and SOD activities in the liver and the kidney tissue homogenates were significantly increased in $CCl_4$ group compared to normal group. But they were decreased significantly in the tocopherol group and tocopherol-ascorbate group compared to $CCl_4$ group. In view of this study tocopherol and ascorbated were ascorbate were effective on the detoxication of liver and kidney injury.

• Childhood Kidney Diseases
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• 제27권2호
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• pp.64-69
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• 2023

Membranoproliferative glomerulonephritis (MPGN) is a complex group of renal diseases characterized by a specific pattern of glomerular injury that includes thickening of the capillary wall and mesangial expansion, leading to a heterogeneous group of conditions. This review article offers a comprehensive overview of MPGN, its new classification, pathophysiology, diagnostic evaluation, and management options.

• 대한임상독성학회지
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• 제19권1호
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• pp.59-63
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• 2021

Copper sulfate is widely used as a fungicide and pesticide. Acute copper sulfate poisoning is rare but potentially lethal in severe cases. Copper sulfate can lead to cellular damage of red blood cells, hepatocytes, and myocytes. Toxic effects include intravascular hemolysis, acute tubular necrosis and, rhabdomyolysis. A 76-year-old man presented with vomiting and epigastric pain. He had ingested a copper-containing fungicide (about 13.5 g of copper sulfate) while attempting suicide 2 hours prior to presentation. From day 3 at the hospital, laboratory findings suggesting intravascular hemolysis were noted with increased serum creatinine level. He was treated with a chelating agent, dimercaptosuccinic acid (succimer). His anemia and acute kidney injury gradually resolved with a 19-day regimen of succimer. Our case suggests that succimer can be used for copper sulfate poisoning when other chelating agents are not available.

• Journal of Trauma and Injury
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• 제34권3호
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• pp.198-202
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• 2021

Super-selective renal artery embolization is an increasingly popular technique for the management of traumatic, low-grade renal trauma. When performed in distal arterial branches, this intervention enables tissue preservation and arrest of hemorrhage, but it may not be practical in cases of multifocal, high-grade renal injuries. In such cases, surgical nephrectomy remains the more common treatment modality to ensure hemodynamic control. We present the unique case of a patient who presented in hemorrhagic shock following a major trauma that resulted in a grade 5 renal injury treated with complete renal artery embolization using Gelfoam, resulting in hemodynamic stabilization. Interestingly, imaging 1 month after embolization revealed residual enhancement of the inferior pole of the kidney, suggesting reconstitution of flow and partial renal salvage. Ultimately, transcatheter "nephrectomy" with careful selection of a temporary embolic agent may serve as a safe and efficient alternative to surgical nephrectomy with the added possibility of preserving partial renal perfusion and function in the emergent setting.

• Molecules and Cells
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• 제42권12호
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• pp.893-905
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• 2019

Mitochondria are highly dynamic organelles that constantly undergo fission and fusion processes that closely related to their function. Disruption of mitochondrial dynamics has been demonstrated in acute kidney injury (AKI), which could eventually result in cell injury and death. Previously, we reported that augmenter of liver regeneration (ALR) alleviates renal tubular epithelial cell injury. Here, we gained further insights into whether the renoprotective roles of ALR are associated with mitochondrial dynamics. Changes in mitochondrial dynamics were examined in experimental models of renal ischemia-reperfusion (IR). In a model of hypoxia-reoxygenation (HR) injury in vitro, dynamin-related protein 1 (Drp1) and mitochondrial fission process protein 1 (MTFP1), two key proteins of mitochondrial fission, were downregulated in the Lv-ALR + HR group. ALR overexpression additionally had an impact on phosphorylation of Drp1 Ser637 during AKI. The inner membrane fusion protein, Optic Atrophy 1 (OPA1), was significantly increased whereas levels of outer membrane fusion proteins Mitofusin-1 and -2 (Mfn1, Mfn2) were not affected in the Lv-ALR + HR group, compared with the control group. Furthermore, the mTOR/4E-BP1 signaling pathway was highly activated in the Lv-ALR + HR group. ALR overexpression led to suppression of HR-induced apoptosis. Our collective findings indicate that ALR gene transfection alleviates mitochondrial injury, possibly through inhibiting fission and promoting fusion of the mitochondrial inner membrane, both of which contribute to reduction of HK-2 cell apoptosis. Additionally, fission processes are potentially mediated by promoting tubular cell survival through activating the mTOR/4E-BP1 signaling pathway.

• Journal of Yeungnam Medical Science
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• 제38권2호
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• pp.136-141
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• 2021

Background: Postoperative acute kidney injury (AKI), which increases the risk of postoperative morbidity and mortality, poses a major concern to surgeons. We conducted this study to analyze the risk factors associated with the occurrence of AKI after orthopedic surgery. Methods: This was a retrospective study that included 351 patients who underwent total hip or knee replacement surgery at Inje University Haeundae Paik Hospital between January 2012 and December 2016. Results: AKI occurred in 13 (3.7%) of the 351 patients. The patients' preoperative estimated glomerular filtration rate (eGFR) was 66.66 ±34.02 mL/min/1.73 m² in the AKI group and 78.07±21.23 mL/min/1.73 m² in the non-AKI group. The hemoglobin levels were 11.21±1.65 g/dL in the AKI group and 12.39±1.52 g/dL in the non-AKI group. Hemoglobin level was related to increased risk of AKI (odds ratio [OR], 0.13; 95% confidence interval [CI], 0.02-0.68; p=0.016). Administration of crystalloid or colloid fluid alone and the perioperative amount of fluid did not show any significant relationship with AKI. Further analysis of the changes in eGFR was performed using a cutoff value of 7.54. The changes in eGFR were significantly related to decreased risk of AKI (OR, 0.74; 95% CI, 0.61-0.89; p=0.002). Conclusion: Renal function should be monitored closely after orthopedic surgery if patients have chronic kidney disease and low hemoglobin level. Predicting the likelihood of AKI occurrence, early treatment of high-risk patients, and monitoring perioperative laboratory test results, including eGFR, will help improve patient prognosis.

• Biomolecules & Therapeutics
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• 제31권1호
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• pp.97-107
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• 2023

Aristolochic acid (AA), extracted from Aristolochiaceae plants, plays an essential role in traditional herbal medicines and is used for different diseases. However, AA has been found to be nephrotoxic and is known to cause aristolochic acid nephropathy (AAN). AA-induced acute kidney injury (AKI) is a syndrome in AAN with a high morbidity that manifests mitochondrial damage as a key part of its pathological progression. Melatonin primarily serves as a mitochondria-targeted antioxidant. However, its mitochondrial protective role in AA-induced AKI is barely reported. In this study, mice were administrated 2.5 mg/kg AA to induce AKI. Melatonin reduced the increase in Upro and Scr and attenuated the necrosis and atrophy of renal proximal tubules in mice exposed to AA. Melatonin suppressed ROS generation, MDA levels and iNOS expression and increased SOD activities in vivo and in vitro. Intriguingly, the in vivo study revealed that melatonin decreased mitochondrial fragmentation in renal proximal tubular cells and increased ATP levels in kidney tissues in response to AA. In vitro, melatonin restored the mitochondrial membrane potential (MMP) in NRK-52E and HK-2 cells and led to an elevation in ATP levels. Confocal immunofluorescence data showed that puncta containing Mito-tracker and GFP-LC3A/B were reduced, thereby impeding the mitophagy of tubular epithelial cells. Furthermore, melatonin decreased LC3A/B-II expression and increased p62 expression. The apoptosis of tubular epithelial cells induced by AA was decreased. Therefore, our findings revealed that melatonin could prevent AA-induced AKI by attenuating mitochondrial damage, which may provide a potential therapeutic method for renal AA toxicity.