• Biomolecules & Therapeutics
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• v.31 no.1
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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.

• Journal of Acupuncture Research
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• v.31 no.2
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• pp.65-74
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• 2014

Objectives : The purpose of this study is evaluating the effect of Hoelen Herbal-acupuncture (HO-HA) at $KI_{10}$(Umgok) on Lipopolysaccharide(LPS) induced nephritis in rats. Methods : The experimental rats were assigned to four groups; normal, LPS, saline, HO-HA groups. LPS(2 mg/kg) was administered to the rats in LPS, saline and HO-HA groups to induce acute inflammatory kidney damage. Saline injection and HO-HA were administered at $KI_{10}$ three times a week. Blood samples were taken from the rats for analysis of white blood cell(WBC), neutrophil, blood urea nitrogen(BUN), creatinine TNF-${\alpha}$, CINC-1. Urine samples were taken from the rats for analysis of urinal volume, creatinine and total protein. The kidney samples were taken from the rats for analysis of renal myeloperoxIdase(MPO). Results : HO-HA suppressed the increases of WBC and neutrophils in blood, BUN, creatinine, TNF-${\alpha}$ and CINC-1 in serum, and MPO in kidney of LPS-stimulated rats. In addition, HO-HA inhibited the decrease of urinary volume in LPS-stimulated rats. Conclusions : HO-HA has therapeutic effects on LPS-induced inflammatory kidney damage in rats. Further studies may be needed for clinical use of HO-HA.

• Toxicological Research
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• v.34 no.2
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• pp.133-141
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• 2018

Anti-cancer drugs such as cisplatin and doxorubicin are effectively used more than radiotherapy. Cisplatin is a chemotherapeutic drug, used for treatment of various forms of cancer. However, it has side effects such as ototoxicity and nephrotoxicity. Cisplatin-induced nephrotoxicity increases tubular damage and renal dysfunction. Consequently, we investigated the beneficial effect of cynaroside on cisplatin-induced kidney injury using HK-2 cell (human proximal tubule cell line) and an animal model. Results indicated that $10{\mu}M$ cynaroside diminished cisplatin-induced apoptosis, mitochondrial dysfunction and caspase-3 activation, cisplatin-induced upregulation of caspase-3/MST-1 pathway decreased by treatment of cynaroside in HK-2 cells. To confirm the effect of cynaroside on cisplatin-induced kidney injury in vivo, we used cisplatin exposure animal model (20 mg/kg, balb/c mice, i.p., once a day for 3 days). Renal dysfunction, tubular damage and neutrophilia induced by cisplatin injection were decreased by cynaroside (10 mg/kg, i.p., once a day for 3 days). Results indicated that cynaroside decreased cisplatin-induced kidney injury in vitro and in vivo, and it could be used for improving cisplatin-induced side effects. However, further experiments are required regarding toxicity by high dose cynaroside and caspase-3/MST-1-linked signal transduction in the animal model.

• Herbal Formula Science
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• v.25 no.2
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• pp.303-324
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• 2017

Objectives : Consumptive is an unhealthy condition that are caused by lack of blood and essence, and that means also some stages of chronic diseases. The purpose of this study is to analysis 108 Prescriptions of Consumptive part in Dongui Bogam. Methods : The 108 Prescriptions of Consumptive part in Dongui Bogam analysed frequency of basic prescriptions, symptoms of prescriptions and the pathology. Results : Ssangbohwan, Yiuihwan, Gamrihwan were used for tonifying were mostly used as basic prescriptions in whole Consumptive part respectively. There are common symptoms in consumptive part in Dongui Bogam. That symptoms are "tidal fever, night sweating, nocturnal emission, cough, sputum, skinny body, weak pulse, spontaneous sweating, deafness, dim vision and tuberculosis". Qi blood(yin yang) pathologies in prescriptions on consumptive part are "yin deficiency, yin deficiency with effulgent fire, yang qi deficiency, dual damage of qi and blood, non-interaction between fire and water, collapse of yang and exhaustion of yin, less blood". viscera and bowels pathologies in prescriptions on consumptive part are "heart and kidney deficiency, spleen-stomach weakness, spleen and kidney great deficiency, weakness of kidney qi, meridian waste in heart, spleen and kidney, damage in heart and lung". Conclusions : As a result of Study on Analysis all Prescriptions of Consumptive part in Dongui Bogam, We can understand more about basic prescriptions, symptoms of prescriptions and the pathology that are using for curing consumptive. We expected that this study will can help to give rationale for future study of consumptive caring.

• Toxicological Research
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• v.32 no.1
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• pp.47-56
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• 2016

The identification of biomarkers for the early detection of acute kidney injury (AKI) is clinically important. Acute kidney injury (AKI) in critically ill patients is closely associated with increased morbidity and mortality. Conventional biomarkers, such as serum creatinine (SCr) and blood urea nitrogen (BUN), are frequently used to diagnose AKI. However, these biomarkers increase only after significant structural damage has occurred. Recent efforts have focused on identification and validation of new noninvasive biomarkers for the early detection of AKI, prior to extensive structural damage. Furthermore, AKI biomarkers can provide valuable insight into the molecular mechanisms of this complex and heterogeneous disease. Our previous study suggested that pyruvate kinase M2 (PKM2), which is excreted in the urine, is a sensitive biomarker for nephrotoxicity. To appropriately and optimally utilize PKM2 as a biomarker for AKI requires its complete characterization. This review highlights the major studies that have addressed the diagnostic and prognostic predictive power of biomarkers for AKI and assesses the potential usage of PKM2 as an early biomarker for AKI. We summarize the current state of knowledge regarding the role of biomarkers and the molecular and cellular mechanisms of AKI. This review will elucidate the biological basis of specific biomarkers that will contribute to improving the early detection and diagnosis of AKI.

• Journal of Microbiology and Biotechnology
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• v.32 no.6
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• pp.740-748
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• 2022

As circ_UBE2D2 has been confirmed to have targeted binding sites with multiple miRNAs involved in septic acute kidney injury (SAKI), efforts in this study are directed to unveiling the specific role and relevant mechanism of circ_UBE2D2 in SAKI. HK-2 cells were treated with lipopolysaccharide (LPS) to construct SAKI model in vitro. After sh-circ_UBE2D2 was transfected into cells, the transfection efficiency was detected by qRT-PCR, cell viability and apoptosis were determined by MTT assay and flow cytometry, and expressions of Bcl-2, Bax and Cleaved-caspase 3 were quantified by western blot. Target genes associated with circ_UBE2D2 were predicted using bioinformatics analysis. After the establishment of SAKI rat model, HE staining and TUNEL staining were exploited to observe the effect of circ_UBE2D2 on tissue damage and cell apoptosis. The expression of circ_UBE2D2 was overtly elevated in LPS-induced HK-2 cells. Sh-circ_UBE2D2 can offset the inhibition of cell viability and the promotion of cell apoptosis induced by LPS. Circ_UBE2D2 and miR-370-3p as well as miR-370-3p and NR4A3 have targeted binding sites. MiR-370-3p inhibitor reversed the promoting effect of circ_UB2D2 silencing on viability of LPS-treated cells, but shNR4A3 neutralized the above inhibitory effect of miR-370-3p inhibitor. MiR-370-3p inhibitor weakened the down-regulation of NR4A3, Bax and Cleaved caspase-3 and the up-regulation of Bcl-2 induced by circ_UB2D2 silencing, but these trends were reversed by shNR4A3. In addition, sh-circ_UBE2D2 could alleviate the damage of rat kidney tissue. Circ_UBE2D2 mitigates the progression of SAKI in rats by targeting miR-370-3p/NR4A3 axis.

• Korean Journal of Veterinary Research
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• v.54 no.4
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• pp.225-231
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• 2014

Klotho deficiency is an early event in acute kidney injury (AKI) that exacerbates acute kidney damage. The present study explored the expression of Klotho and inflammation related factors in cisplatin-induced AKI. Rats (n = 18) were treated with cisplatin intraperitoneal injection (5 mg/kg) or left untreated as controls (n = 6), then sacrificed at 5 (n = 6) and 10 days (n = 6) treatment. Five days after cisplatin injection, the serum kidney enzymes and kidney cell apoptosis were significantly increased. Moreover, the expression of Klotho was decreased when compared to the control group, especially in the cortex and outer medulla regions. In contrast, inflammation related signals including nuclear factor kappa B, tumor necrosis factor-${\alpha}$, and tumor necrosis factor-like weak inducer of apoptosis were enhanced. However, 10 days after cisplatin injection, Klotho expression was enhanced upon both IHC and Western blot analysis, with slightly recovered renal function and decreased apoptosis. Furthermore, inflammation related signals expression was decreased relative to the 5 days group. Overall, this study confirmed the opposite expression patterns between Klotho and inflammation related signals and their localization in cisplatin-induced AKI kidney.

• Journal of Nutrition and Health
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• v.34 no.7
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• pp.734-740
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• 2001

The purpose of this study was to investigate the effect of green tea catechins on the antioxidative defense enzyme activity of kidney in diabetic rats. Sprague-Dawley male rats weighting 100$\pm$10g were randomly assigned to one normal and three STZ-induced diabetic groups; catechin free diet(DM-0C group), 0.25% catechin diet(DM-0.25C group) and 0.5% catechin diet(DM-0.5C group). Diabetes was induced by intravenous of 55mg/Kg body weight of STZ in sodium citrate buffer(pH 4.3) after 4 weeks feeding of experimental diets. Rats were sacrified at the 6th day of diabetic states. Superoxide dismutase(SOD) activity in kidney was decreased by 25% and 20% in DM-0C and DM-0.25C groups compared with normal group, DM-0.5C group was not significantly different when compared with normal group. Glutathione peroxidase(GSHpx) activity in kidney was were no significant differences the diabetic groups compared to normal group. Xanthin oxidase(XOD) activity was increased by 110% and 63% in DM-0C and DM-0.25C groups compared with normal group, DM-0.5C group was not significantly different when compared with normal group. The contents of superoxide radical(O$_2$)in kindney were 116% and 33%, respectively, higher in DM-0C and DM-0.25C groups than normal group. DM-0.5C group and normal groups were similar levels in their superoxide radical contents of kidneys. Levels of TBARS(thiobarbituric acid reactive substance) in kidney were increased by 62% in DM-0C group, when compared with normal group, but those of DM-0.5C group were similar to that of normal groups. These results indicate that free radical generation system was weakened and free radical scavenger system was enhance in kidney of STZ-induced diabetics rats by dietary catechin. Thereby it may reduce renal disorders such as oxidative damage and aging of tissue.

• Journal of Ginseng Research
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• v.41 no.2
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• pp.227-231
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• 2017

Background: Ginsenosides are active components of Panax ginseng that exert various health benefits including kidney protection effect. The medicinal activity of ginsenosides can be enhanced by modulating their stereospecificity by heat processing. Ginsenosides Rk2 and Rh3 represent positional isomers of the double bond at C-20(21) or C-20(22). Methods: The present study investigated the kidney-protective effects of ginsenosides Rk2 and Rh3 against cisplatin, a platinum based anticancer drug, induced apoptotic damage in renal proximal LLC-PK1 cells. Results: As a result, ginsenoside Rh3 shows a stronger protective effect than that shown by Rk2. Cisplatin-induced elevated protein levels of phosphorylated c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase (ERK), p38, and cleaved caspase-3 decreased after cotreatment with ginsenoside Rh3. The increase in the percentage of apoptotic LLC-PK1 cells induced by cisplatin treatment also significantly reduced after cotreatment with ginsenoside Rh3. Conclusion: These results demonstrate that inhibition of the JNK and ERK mitogen-activated protein kinase signaling cascade plays a critical role in mediating the renoprotective effect of ginsenoside Rh3.

• Journal of Physiology & Pathology in Korean Medicine
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• v.18 no.6
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• pp.1784-1794
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• 2004

To study the effects between Cd inhalation toxicity and methanol extract of Radix Achyranthis Bidentatae, 4 rat groups were exposed to Cd aerosol by whole-body inhalation exposure for 6 hours/day, 5 days/week, and 4 weeks. Cd concentration in air was 0.98㎎/㎥ and mass median diameter(MMD) was 1.78㎛. 3 different dose intraperitoneal injections of methanol extract of Radix Achyranthis Bidentatae to 3 inhalation exposure groups applied for 4 weeks and the results were as follows: The highest body weight gain for 4 weeks and food intake per day were from inhalation exposure group Ⅲ(p<0.05). The highest lung weight was from inhalation exposure group Ⅲ and the highest liver and kidney weight were from inhalation exposure group Ⅱ(p<0.05). The lowest Cd content in lung was 22.77㎍/g from inhalation exposure group Ⅲ(p<0.05). The highest Cd concentration in blood was 11.71㎍/㎗ from inhalation exposure group Ⅰ(p<0.05). Cd concentrations of 14.87㎍/g in liver and 17.91㎍/g in kidney were the highest from inhalation exposure group Ⅰ(p<0.05). The lowest Cd concentration in liver and kidney were 5.71㎍/g and 3.17㎍/g from the control(p<0.05). For weekly Cd concentration in urine, the highest value was 0.48㎍/㎖ from inhalation exposure group Ⅲ of the 3rd week and inhalation exposure group Ⅰ, Ⅱ of the 4th week. For weekly Cd concentration in feces, the highest value was 0.32㎍/g from inhalation exposure group Ⅰ, Ⅱ, Ⅲ. The highest metallothionein concentration in lung was 89.02㎍/g from inhalation exposure group Ⅲ(p<0.05). The highest metallothionein concentrations in liver and kidney were 265.47㎍/g and 214.21㎍/g from inhalation exposure group Ⅲ, respectively(p<0.05). The highest Hct, Hb, and WBC values were from inhalation exposure group Ⅱ and the highest RBC value was from inhalation exposure group Ⅲ(p<0.05). Mostly damaged part in liver tissue was hepatic lobule and the degrees of damage were lessened by the intraperitoneal injection of methanol extract of Radix Achyranthis Bidentatae. Proximal, distal convoluted tubules and glomerulus in kidney tissue were mostly damaged part. Degeneration and swelling were partially observed but the degrees of kidney tissue damage were lessened more or less by the intraperitoneal injection of methanol extract of Radix Achyranthis Bidentatae.