• 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.

• KSBB Journal
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• v.23 no.5
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• pp.381-386
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• 2008

Lipophilic ammonia is toxic gas and can easily diffuse across cell membranes. Excess ammonia is implicated in the pathogenesis of several metabolic disorders including hepatic encephalopathy and may result in the death. The purpose of this study was to clarify the inhibition effect of metronidazole on liver cell damage due to ammonia in human Hep G2 cell and rat hepatocytes. The effects of metronidazole were studied in ammonium chloride treated human Hep G2 cell (75 mM) and rat hepatocyte (100 mM) following $0.1{\mu}M$ metronidazole treatment. In MTZ+AC group, cell viabilities increased prominently and LDH activities decreased over 25% than AC group. Furthermore, ammonia level according to ammonium chloride treatment reduced over 30% and lipid peroxidation as an index of cell membrane damage decreased more than twice. By comparison with control, catalase activity showed more than 30% reduction in AC group while less than 10% reduction in MTZ+AC group, respectively. In addition, MTZ+AC group showed the similar cell structure as control in cell morphology study by using light microscope, and represented fluorescent intensity decrement compared with AC group in fluorescent microscopic study with avidin-TRITC fluorescent dye. And cleaved PARP expression due to ammonia reduced twofold or more in MTZ+AC group. As the results suggest, metronidazole may protect the liver cell by inhibiting cell damages due to ammonia and be used for an effective antagonist of ammonia in hyperammonemia.

• BMB Reports
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• v.42 no.10
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• pp.648-654
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• 2009

Overexpression of phospholipid hydroperoxide glutathione peroxidase (PHGPx) genes has been reported to play an important role in protecting host cells from oxidative injury in several model systems. A radish phospholipid hydroperoxide glutathione peroxidase (RsPHGPx) known to have high catalytic activity was applied to mouse 3T3 fibroblasts to determine the protective effects of PHGPx against oxidative injury triggered by hydroperoxides such as hydrogen peroxide ($H_2O_2$), tert-butyl hydroperoxide (t-BHP) and phosphatidylcholine hydroperoxide (PCOOH). We observed that preincubation of cells with RsPHGPx significantly increased cell viability, reduced levels of malondialdehyde (MDA), inhibited generation of reactive oxygen species (ROS), and maintained natural cell shapes after treatment with $H_2O_2$, t-BHP or PCOOH, indicating that the exogenous RsPHGPx can act as an effective hydroperoxide-scavenger and may also protect target cells from oxidative damage. These results suggest the possibility for use of RsPHGPx as a therapeutic protectant.

• The Plant Pathology Journal
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• v.32 no.2
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• pp.157-161
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• 2016

Gamma irradiation was evaluated for its in vitro and in vivo antibacterial activity against a postharvest bacterial pathogen, Erwinia carotovora subsp. carotovora (Ecc). Gamma irradiation in a bacteria cell suspension resulted in a dramatic reduction of the viable counts as well as an increase in the amounts of DNA and protein released from the cells. Gamma irradiation showed complete inactivation of Ecc, especially at a dose of 0.6 kGy. In addition, scanning electron microscopy of irradiated cells revealed severe damage on the surface of most bacterial cells. Along with the morphological changes of cells by gamma irradiation, it also affected the membrane integrity in a dose-dependent manner. The mechanisms by which the gamma irradiation decreased the bacterial soft rot can be directly associated with the disruption of the cell membrane of the bacterial pathogen, along with DNA fragmentation, results in dose-dependent cell inactivation. These findings suggest that gamma irradiation has potential as an antibacterial approach to reduce the severity of the soft rot of paprika.

• Journal of Microbiology and Biotechnology
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• v.31 no.6
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• pp.867-874
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• 2021

Epalrestat (EPS) is a brain penetrant aldose reductase inhibitor, an approved drug currently used for the treatment of diabetic neuropathy. At near-plasma concentration, EPS induces glutathione biosynthesis, which in turn reduces oxidative stress in the neuronal cells. In this study, we found that EPS reduces neurodegeneration by inhibiting reactive oxygen species (ROS)-induced oxidative injury, mitochondrial membrane damage, apoptosis and tauopathy. EPS treatment up to 50 µM did not show any toxic effect on SH-SY5Y cell line (neuroblastoma cells). However, we observed toxic effect at a concentration of 100 µM and above. At 50 µM concentration, EPS showed better antioxidant activity against H₂O₂ (100 µM)-induced cytotoxicity, ROS formation and mitochondrial membrane damage in retinoic acid-differentiated SH-SY5Y cell line. Furthermore, our study revealed that 50 µM of EPS concentration reduced the glycogen synthase kinase-3 β (GSK3-β) expression and total tau protein level in H₂O₂ (100 µM)-treated cells. Findings from this study confirms the therapeutic efficacy of EPS on regulating Alzheimer's disease (AD) by regulating GSK3-β and total tau proteins phosphorylation, which helped to restore the cellular viability. This process could also reduce toxic fibrillary tangle formation and disease progression of AD. Therefore, it is our view that an optimal concentration of EPS therapy could decrease AD pathology by reducing tau phosphorylation through regulating the expression level of GSK3-β.

• Biomolecules & Therapeutics
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• v.21 no.4
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• pp.270-276
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• 2013

Fucoxanthin is an important carotenoid derived from edible brown seaweeds and is used in indigenous herbal medicines. The aim of the present study was to examine the cytoprotective effects of fucoxanthin against hydrogen peroxide-induced cell damage. Fucoxanthin decreased the level of intracellular reactive oxygen species, as assessed by fluorescence spectrometry performed after staining cultured human HaCaT keratinocytes with 2',7'-dichlorodihydrofluorescein diacetate. In addition, electron spin resonance spectrometry showed that fucoxanthin scavenged hydroxyl radical generated by the Fenton reaction in a cell-free system. Fucoxanthin also inhibited comet tail formation and phospho-histone H2A.X expression, suggesting that it prevents hydrogen peroxide-induced cellular DNA damage. Furthermore, the compound reduced the number of apoptotic bodies stained with Hoechst 33342, indicating that it protected keratinocytes against hydrogen peroxide-induced apoptotic cell death. Finally, fucoxanthin prevented the loss of mitochondrial membrane potential. These protective actions were accompanied by the down-regulation of apoptosis-promoting mediators (i.e., B-cell lymphoma-2-associated ${\times}$ protein, caspase-9, and caspase-3) and the up-regulation of an apoptosis inhibitor (B-cell lymphoma-2). Taken together, the results of this study suggest that fucoxanthin defends keratinocytes against oxidative damage by scavenging ROS and inhibiting apoptosis.

• Journal of the Korean Institute of Intelligent Systems
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• v.14 no.4
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• pp.411-417
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• 2004

Recently, instruments and systems related on biological technology have been enormously developed. Particularly, many researches for biological cell injection have been carried out. Usually, excessive contact force occurring when the end-effector and a biological cell contact might make a damage on the cell. Unfortunately, the excessive force could easily destroy the membrane and tissue of the cell. In order to overcome the problem, we proposed a new injection system for biological cell manipulation. The proposed injection system can measure the contact force between a pipette and a cell by using a force sensor. Also, we used vision technology to correctly guide the tip of the pipette to the cell. Consequently, the proposed injection system could safely manipulate the biological cells without any damage. This paper presents the introduction of our new injection system and design concepts of the new micro end-effector. Through a series of experiments the proposed injection system shows the possibility of application for precision biological cell manipulation such as DNA operation.

• Proceedings of the Korean Vacuum Society Conference
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• 2016.02a
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• pp.208.2-208.2
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• 2016

Many researchers have paid attention to the studies on the interaction between non-thermal plasma and aqueous solutions for biomedical applications. The gas composition in the plasma is very important. Oxygen and nitrogen are the main gases of interest in biological applications. Especially, we focus on the oxygen concentration. In this experiment, we studied the role of oxygen concentration in plasma induced chemical reactions in solution. At first, the amount of ions are measured according to changing the oxygen concentration. And we checked the relationship between these ions and pH value. Secondly, when the oxygen concentration is changed, it identified the type and amount of radical generated by the plasma. In order to confirm the effect of these chemical property change to biological material, hemoglobin and RBCs are chosen. RBCs are one of the common basic biological cells. Thirdly, when plasma treated according to oxygen concentration in nitrogen feeding gas, oxidation of hemoglobin and RBC is checked. Finally, membrane oxidation of RBC is measured to examine the relation between hemoglobin oxidation and membrane damage through relative hemolysis and Young's modulus. Our results suggest that reactive species generated by the plasma differsdepending on the oxygen concentration changes. The pH values are decreased when oxygen concentration increased. OH decrease and NO increase are also observed. These reactive species makes change of chemical properties of solution. We also able to confirm that the difference in these reactive species to affect the oxidation of the Hb and RBCs. The Hb and RBCs are more oxidized with the high oxygen concentration conditions. But membrane is damaged more by plasma treatment with only nitrogen gas. It is shown that red blood cells membrane damage and oxidation of hemoglobin are not directly related.

• Clinical and Experimental Pediatrics
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• v.48 no.5
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• pp.545-550
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• 2005

Purpose : Newborn brain tissue has to be dissociated into a single cell suspension for flow cytometric analysis of cell death during hypoxia-ischemia. Thus the development of a method to dissociate cells from the brain tissue with least damage and maintenance of membrane and antigen integrity remains the challenge for the in vivo application of this technique. We evaluated the efficacy of mechanical or enzymatic (collagenase or tryspin) methods of brain tissue disaggregation. Methods : The extent of the damage to the plasma membrane and loss of the characteristics of the membrane induced with each dissociation method was determined by comparing the flow cytometric results labeled with both fluorescent annexin V and propidium iodide of the newborn rat pup brain tissue in the control group (n=10) and in the 48-hour after hypoxia-ischemia group (n=10). Results : In the control group, the cell percentage of damaged, apoptotic and necrotic cells of both hemispheres with the mechanical dissociation method was significantly increased compared to the trypsin or collagenase method. In the 48-hour after hypoxia-ischemia group, the cell percentage of apoptotic and necrotic cells of the right hemisphere with the collagenase method significantly increased, and live cells significantly decreased compared to the left hemisphere, control group. Although the same trend was observed, the extent of alterations made with the trypsin method was significantly less compared to the collagenase method. Conclusion : The dissociation of neonatal brain tissue for flow cytometric analysis with collagenase was most efficacious with the least cell damage and preservation of the plasma membrane characteristics.

• Korean Journal of Microbiology
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• v.50 no.4
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• pp.360-367
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• 2014

Candida albicans is an opportunistic and the most prevalent fungal pathogen that can cause superficial and systemic infections in immunocompromised patients. C. albicans can promote the transition from budding yeast to filamentous form, generating biofilms. Infections associated with C. albicans biofilms are frequently resistant to conventional antifungal therapy. Therefore, the development of more effective antifungal drugs related with biofilm formation is required urgently. The roots of Rheum undulatum have been used for medicinal purposes in Korea and China traditionally. The aim of present study was to evaluate the effect of R. undulatum extract upon preformed biofilms of 12 clinical C. albicans isolates and the antifungal activities. Its effect on preformed biofilms was evaluated using XTT reduction assay, and metabolic activity of all tested strains was reduced significantly ($49.4{\pm}6.0%$) at 0.098 mg/ml R. undulatum. The R. undulatum extract blocked the adhesion of C. albicans biofilms to polystyrene surfaces, and damaged the cell membrane integrity of C. albicans which was analyzed by CFDA, AM, and propidium iodide double staining. It caused cell lysis which was observed by Confocal laser scanning and phase contrast microscope after propidium iodide and neutral red staining, respectively. Membrane permeability was changed as evidenced by crystal violet uptake. The data suggest that R. undulatum inhibits biofilm formation by C. albicans, which can be associated with the damage of the cell membrane integrity, the changes in the membrane permeability and the cell lysis of C. albicans.