• 대한의생명과학회지
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• 제9권4호
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• pp.189-193
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• 2003

This study was undertaken to investigate the effect of baicalein, a major flavone component of Scutellaria balicalensis Georgi, on oxidant-induced cell injury in renal epithelial cells. Opossum kidney cells, an established proximal tubular epithelial cells, were used as a cell model of renal epithelial cells and t-butylhydroperoxide (tBHP) as an oxidant drug model. Cell viability was measured by MTT assay and lipid peroxidation was estimated by measuring the content of malondialdehyde, a product of lipid peroxidation. Exposure of cells to tBHP caused cell death and its effect was dose-dependent over concentration range of 0.1~1.0 mM. When cells were exposed to tBHP in the presence of various concentrations (0.1~10 $\mu$M) of baicalein, tBHP-induced cell death was prevented with a manner dependent of baicalein concentration. tBHP induced A TP depletion, which was significantly prevented by baicalein. Similarly, tBHP-induced DNA damage was prevented by baicalein. tBHP produced a marked increase in lipid peroxidation and its effect was completely inhibited by baicalein. These results indue ate that tBHP induces cell injury through a lipid peroxidation-dependent mechanism in renal epithelial cells, and baicalein prevented oxidant-induced cell injury via antioxidant action inhibiting lipid peroxidation. In addition, these results suggest that baicalein may be a candidate for development of drugs which are effective in preventing and treating renal diseases.

• 대한임상검사과학회지
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• 제42권1호
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• pp.46-54
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• 2010

Ceramide induces cell death in a variety of cell types however, the underlying molecular mechanisms related to renal epithelial cells remain unclear. The present study was undertaken to determine the role of extracellular signal-regulated protein kinase (ERK) in ceramide-induced cell death in renal epithelial cells. An established renal proximal tubular cell line of opossum kidney (OK) cells was used for this research. Ceramide induced apoptotic cell death in these cells. Western blot analysis showed that ceramide induced activation of ERK. The ERK activation and cell death induced by ceramide were prevented by the ERK inhibitor PD98059. Ceramide caused cytochrome C release from mitochondria into the cytosol as well as activation of caspase-3. Both effects were prevented by PD98059. The ceramide-induced cell death was also prevented by a caspase inhibitor. These results suggest that ceramide induces cell death through an ERK-dependent mitochondrial apoptotic pathway in OK cells.

• Childhood Kidney Diseases
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• 제10권1호
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• pp.1-7
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• 2006

Osteopontin (OPN) is a glycosylated phosphoprotein which mediates cell adhesion and migration, and is produced by bone, macrophages, endothelial cells, and epithelial cells. The many regulatory functions of OPN include bone remodeling, tumor invasion, wound repair, and promotion of cell survival. It is produced by renal tubular epithelial cells, and expression is upregulated in glomerulonephritis, hypertension, ischemic acute renal failure, renal ablation, and UUO. In this review, we discuss about osteopontin in general aspect, expression, role on the development and pathologic condition of neonatal kidney.

• The Korean Journal of Physiology and Pharmacology
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• 제27권6호
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• pp.533-540
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• 2023

Sweroside is a natural monoterpene derived from Swertia pseudochinensis Hara. Recently, studies have shown that sweroside exhibits a variety of biological activities, such as anti-inflammatory, antioxidant, and hypoglycemic effects. However, its role and mechanisms in high glucose (HG)-induced renal injury remain unclear. Herein, we established a renal injury model in vitro by inducing human renal tubular epithelial cell (HK-2 cells) injury by HG. Then, the effects of sweroside on HK-2 cell activity, inflammation, reactive oxygen species (ROS) production, and epithelial mesenchymal transition (EMT) were observed. As a result, sweroside treatment ameliorated the viability, inhibited the secretion of inflammatory cytokines (TNF-α, IL-1β, and VCAM-1), reduced the generation of ROS, and inhibited EMT in HK-2 cells. Moreover, the protein expression of SIRT1 was increased and the acetylation of p65 NF-kB was decreased in HK-2 cells with sweroside treatment. More importantly, EX527, an inhibitor of SIRT1, that inactivated SIRT1, abolished the improvement effects of sweroside on HK-2 cells. Our findings suggested that sweroside may mitigate HG-caused injury in HK-2 cells by promoting SIRT1-mediated deacetylation of p65 NF-kB.

• 한국어병학회지
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• 제36권2호
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• pp.415-422
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• 2023

In veterinary medicine for mammals, studies are being conducted to confirm the effects of antioxidants using pathological toxicity model studies, and are also used to confirm the effect of mitigating liver or kidney toxicity of specific substances. It was considered necessary to study such a toxicity model for domestic farmed fish, so thioacetamide (TAA), a toxic substance that causes tissue damage by mitochondrial dysfunction, was injected into rainbow trout (Oncorhynchus mykiss), a major farmed freshwater fish species in Korea. The experiment was conducted with 40 rainbow trout (Oncorhynchus mykiss) weighting 53 ± 0.6 g divided into two groups. Thioacetamide(TAA) 300mg/kg of body weight was intraperitoneally injected into rainbow trout and samples were taken 1, 3, 5, 7 days after peritoneal injection. As a result, in serum biochemical analysis, AST levels related to liver function decreased 3 and 5 days after intraperitoneal injection and increased after 7 days, and ALT levels also increased after 7 days. In addition, creatinine related to renal malfunction increased 3 and 5 days after TAA injection. In histopathological analysis, pericholangitis and local lymphocyte infiltration were observed in the liver from 1 day after intraperitoneal injection of TAA, and hepatic parenchymal cell necrosis was also observed from 3 days after intraperitoneal injection. Hyaline droplet in renal tubular epithelial cell was observed from 1 day after TAA injection, and acute tubular damage such as tubular epithelial cell necrosis appeared from 3 days after TAA injection. Accordingly, it is thought that it will be able to contribute to studies that require a toxicity model.

• The Korean Journal of Physiology and Pharmacology
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• 제2권1호
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• pp.69-76
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• 1998

Cis-diamminedichloroplatinum II (cisplatin), an effective antitumor agent, induces acute renal failure by unknown mechanisms. To investigate direct toxic effects of cisplatin in the renal proximal tubular transport system, OK cell line was selected as a cell model and $Na^+/H^+$ antiport activity was evaluated during a course of cisplatin treatment. The cells grown to confluence were treated with cisplatin for 1 hour, washed, and incubated for up to 48 hours. At appropriate intervals, cells were examined for $Na^+/H^+$ antiport activity by measuring the recovery of intracellular pH (pHi) after acid loading. Cisplatin of less than 50 ${\mu}M$ induced no significant changes in cell viability in 24 hours, but it decreased the viability markedly after 48 hours. In cells exposed to 50 ${\mu}M$ cisplatin for 24 hours, the $Na^+-dependent$ pHi recovery (i.e., $Na^+/H^+$ antiport) was drastically inhibited with no changes in the $Na^+-independent$ recovery. Kinetic analysis of the $Na^+-dependent$ pHi recovery indicated that the Vmax was reduced, but the apparent Km was not altered. The cellular $Na^+$ and $K^+$ contents determined immediately before the transport measurement appeared to be similar in the control and cisplatin group, thus, the driving force for $Na^+-coupled$ transport was not different. These results indicate that cisplatin exposure impairs the $Na^+/H^+$ antiport capacity in OK cells. It is, therefore, possible that in patients treated with a high dose of cisplatin, proximal tubular mechanism for proton secretion (hence $HCO_3^-$ reabsorption) could be attenuated, leading to a metabolic acidosis (proximal renal tubular acidosis).

• Preventive Nutrition and Food Science
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• 제17권2호
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• pp.101-108
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• 2012

Interruption or prolonged reduction and subsequent restoration of blood flow into the kidney triggers the generation of a burst of reactive oxygen species (ROS), leading to injury in the tubular epithelial cells. In this study, we determined whether methanol extract of goat's-beard (Aruncus dioicus) (extract) could prevent this ischemia/reperfusion injury. When in vitro radical scavenging activity of the extract was measured using a DPPH radical quenching assay, the extract displayed slightly lower activity than ascorbic acid. One hour after administration of the extract (400 mg/kg) by intraperitoneal injection in rats, renal ischemia/reperfusion injury was generated by clamping the left renal artery for forty minutes, followed by 24 hr restoration of blood circulation. Prior to clamping the left renal artery, the right renal artery was removed. Compared with the vehicle-treated group, pretreatment with the extract significantly reduced the tubular epithelial cell injury by 37% in the outer medulla region, and consequently reduced serum creatinine concentration by 39%. Reduction in the cell injury was mediated by attenuation of Bax/Bcl-2 ratio, inhibition of caspase-3 activation from procaspase-3, and subsequent reduction in the number of apoptotic cells. Thus, goat's-beard (Aruncus dioicus) might be developed as a prophylactic agent to prevent acute kidney injury.

• The Korean journal of internal medicine
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• 제34권1호
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• pp.146-155
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• 2019

Background/Aims: Indoxyl sulfate (IS) is a uremic toxin and an important causative factor in the progression of chronic kidney disease. Recently, paricalcitol (19-nor-1,25-dihydroxyvitamin D2) was shown to exhibit protective effects in kidney injury. Here, we investigated the effects of paricalcitol treatment on IS-induced renal tubular injury. Methods: The fluorescent dye 2',7'-dichlorofluorescein diacetate was used to measure intracellular reactive oxygen species (ROS) following IS administration in human renal proximal tubular epithelial (HK-2) cells. The effects of IS on cell viability were determined using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assays and levels of apoptosis-related proteins (Bcl-2-associated protein X [Bax] and B-cell lymphoma 2 [Bcl-2]), nuclear $factor-{\kappa}B$ ($NF-{\kappa}B$) p65, and phosphorylation of mitogen-activated protein kinase (MAPK) and protein kinase B (Akt) were determined by semiquantitative immunoblotting. The promoter activity of $NF-{\kappa}B$ was measured by luciferase assays and apoptosis was determined by f low cytometry of cells stained with f luorescein isothiocyanate-conjugated Annexin V protein. Results: IS treatment increased ROS production, decreased cell viability and induced apoptosis in HK-2 cells. IS treatment increased the expression of apoptosis-related protein Bax, decreased Bcl-2 expression, and activated phosphorylation of MAPK, $NF-{\kappa}B$ p65, and Akt. In contrast, paricalcitol treatment decreased Bax expression, increased Bcl-2 expression, and inhibited phosphorylation of MAPK, $NF-{\kappa}B$ p65, and Akt in HK-2 cells. $NF-{\kappa}B$ promoter activity was increased following IS, administration and was counteracted by pretreatment with paricalcitol. Additionally, flow cytometry analysis revealed that IS-induced apoptosis was attenuated by paricalcitol treatment, which resulted in decreased numbers of fluorescein isothiocyanate-conjugated Annexin V positive cells. Conclusions: Treatment with paricalcitol inhibited IS-induced apoptosis by regulating MAPK, $NF-{\kappa}B$, and Akt signaling pathway in HK-2 cells.

• 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.

• 한국임상수의학회지
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• 제6권2호
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• pp.319-327
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• 1989

In order to study the effects of neomycin sulfate on the kidney of Korean black goats after dosing at 36mg/kg(A group) or 18mg/kg of body weight (B group) twice a day, serum chemical values(BUN, SCr), urinary enzyme(GGT) excretion and urinary analysis were checked and renal lesions were observed by light microscope. The proteinuria and granular casts were observed on the 5-6th day and 7th day of treatment with neomycin respectively in the A group. While these changes were observed on the 4th day and the 6th day respectively in one goat of the B group. Urinary GGT excretion began to increase from the 9th day and reached to maximum concentration on the 15th day of treatment with neomycin in the A group. Thereafter, GGT excretion began to decrease and reach to normal level on the 21th day. But GGT excretion increased on the 9th day in only one goat of the B group. Concentrations of BUN and SCr increased on the 12th day in the A group and in one goat of B group. The kidneys were swollen gross pathologically and the renal tubular epithelial cell changes were noticed histologically in the A group and in one goat of the B group. These changes were included degeneration with hyaline droplet formation, flattened epithelial cells and necrotic epithelium. Granular casts were showed in many tubular lumens. Prfesent results indicated that nephrotoxicosis would not occured in Korean black goats dosing with neomycin sulfate less that 36mg/kg of body weight a day.