• The Journal of Internal Korean Medicine
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• v.26 no.2
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• pp.420-430
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• 2005

The water extract of Omijatang(OMJT) has been traditionally used for treatment of abscess and heart palpitation in oriental medicine, However, little is known about the mechanism by which the water extract of OMJT rescues cells from these damages. This study was designed to investigate the protective mechanisms of OMJT in H9c2 cardiomyoblasts on oxidative stress-induced cytotoxicity including $H_2O_2,\;ZnCl_2$, hypoxia, and reoxygenation. Oxidative stress markedly decreased the viability of H9c2 cells. This was characterized with apparent apoptotic features such as chromatin condensation as well as fragmentation of genomic DNA and nuclei. However, OMJT significantly reduced $H_2O_2$-induced cell death and apoptotic characteristics as well as $ZnCl_2$, hypoxialreoxygenation. Taken together, this study suggests that the water extract of OMJT has the protective effects against oxidative injuries.

• Biomolecules & Therapeutics
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• v.28 no.5
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• pp.381-388
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• 2020

Methamphetamine (METH) is a highly addictive psychostimulant and one of the most widely abused drugs worldwide. The continuous use of METH eventually leads to drug addiction and causes serious health complications, including attention deficit, memory loss and cognitive decline. These neurological complications are strongly associated with METH-induced neurotoxicity and neuroinflammation, which leads to neuronal cell death. The current review investigates the molecular mechanisms underlying METH-mediated neuronal damages. Our analysis demonstrates that the process of neuronal impairment by METH is closely related to oxidative stress, transcription factor activation, DNA damage, excitatory toxicity and various apoptosis pathways. Thus, we reach the conclusion here that METH-induced neuronal damages are attributed to the neurotoxic and neuroinflammatory effect of the drug. This review provides an insight into the mechanisms of METH addiction and contributes to the discovery of therapeutic targets on neurological impairment by METH abuse.

• Journal of Ginseng Research
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• v.35 no.3
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• pp.339-343
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• 2011

Polycyclic aromatic hydrocarbons (PAHs) are well known environmental carcinogens. PAH metabolites, especially BaP-7,8- dihydrodiol, 9,10 epoxide, initiate carcinogenesis via high specificity binding to DNA to form DNA adducts. The Korean red ginseng (KRG) from Panax ginseng has been suggested to protect against damages due to PAH exposure but the mechanism is unknown. Therefore, we investigated effects of KRG on PAH exposure using toxicokinetic methods and changes of PAH-induced oxidative damage during a 2 week-clinical trial (n=21 healthy young female, $23.71{\pm}2.43$ years). To analyze antioxidative effects of KRG, we measured changes in the levels of urinary malondialdehyde (MDA) before and after KRG treatment. We observed a significant positive association between levels of urinary MDA and 1-hydroxypyrene, a biomarker of PAH exposures (slope=1.47, p=0.03) and confirmed oxidative stress induced by PAH exposures. A reverse significant correlation between KRG treatment and level of urinary MDA was observed (p=0.03). In summary, results of our clinical trial study suggest that KRG plays a significant role in antioxidative as well as toxicokinetic pathways against PAHs exposure.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.44 no.4
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• pp.375-379
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• 2018

In the present study, we have investigated whether methylated marliolide could induce NRF2 thereby exerting anti-oxidant effects. MTT assay showed that methylated marliolide did not exhibit cytotoxicity on HaCaT cells. Methylated marliolide induced a higher ARE-dependent luciferase activation in HaCaT ARE-GFP-luciferase cells, compared with resveratrol. In addition, exposure of methylated marliolide to HaCaT cells significantly induced NRF2 and transcriptionally activated HO-1 and NQO1, both of which are target genes of NRF2. Finally, methylated marliolide protected HaCaT cells against TPA-induced oxidative damages on nucleotides and lipids. Together, results shows that methylated marliolide could suppress oxidative damages through induction of NRF2 which implies that methylated marliolide might serve as a good candidate for novel cosmetic ingredient with anti-oxidant effects.

• Biomedical Science Letters
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• v.15 no.1
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• pp.1-8
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• 2009

Human genomic DNA is continuously attacked by oxygen radicals originated from cellular metabolic processes and numerous environmental carcinogens. 2-deoxyribonolactone (dL) is a major type of oxidized abasic (AP) lesion implicated in DNA strand scission, mutagenesis, and formation of covalent DNA-protein crosslink (DPC) with DNA polymerase (Pol) ${\beta}$. We show here that human DNA polymerase (Pol)${\iota}$ and mitochondrial $Pol{\gamma}$ give rise to stable DNA-protein crosslink (DPC) formation that is specifically mediated by dL lesion. $Pol{\gamma}$ mediates DPC formation at the incised dL residue by its 5'-deoxyribose-5-phosphate (dRP) lyase activity, while $Pol{\gamma}$ cross links with dL thorough its intrinsic dRP lyase and AP lyase activities. Reactivity in forming dL-mediated DPC was significantly higher with $Pol{\gamma}$ than with $Pol{\iota}$. DPC formation by $Pol{\gamma}$, however, can be reduced by an accessory factor of $Pol{\gamma}$ holoenzyme that may attenuate deleterious effects of crosslink adducts on mitochondrial DNA. Comparative kinetic analysis of DPC formation showed that the rate of DPC formation with either $Pol{\iota}$ or $Pol{\gamma}$ was lower than that with $Pol{\beta}$. These results revealed that the activity of catalytic lyase in DNA polymerases determine the efficiency of DPC formation with dL damages. Irreversible crosslink formation of such DNA polymerases by dL lesions may result in a prolonged strand scission and a suicide of DNA repair proteins, both of which could pose a threat to the genetic and structural integrity of DNA.

• Journal of Animal Reproduction and Biotechnology
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• v.38 no.2
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• pp.47-53
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• 2023

Despite numerous advances in in-vitro embryo production (IVP), many documented factors have been shown to influence the development of mammalian preimplantation embryos and the success of IVP. In this sense, elevated levels of reactive oxygen species (ROS) correlate with poor outcomes in assisted reproductive technologies (ART) due to oxidative stress (OS), which results from an imbalance between ROS production and neutralization. Indeed, excessive production of ROS compromises the structural and functional integrity of gametes and embryos both in vivo and in vitro. In particular, OS damages proteins, lipids, and DNA and accelerates cell apoptosis. Several in-vivo and in-vitro studies report an improvement in qualityrelevant parameters after the use of various antioxidants. In this review, we focus on OS and the source of free radicals and their effects on oocytes, sperm, and the embryo during IVP. In addition, antioxidants and their important role in IVP, supplementation during oocyte in vitro maturation (IVM), in vitro culture (IVC), and semen extenders were discussed. Nevertheless, various methods for determining the level of ROS in germ cells have been briefly described. Still, it is crucial to develop standardized antioxidant supplement systems to improve overall IVP success. Further studies should explore the safety, efficacy, mechanism of action, and combination of different antioxidants to improve IVP outcomes.

• Toxicological Research
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• v.14 no.4
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• pp.515-523
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• 1998

Oxidative stress by reactive oxygen species (ROS) damages cellular DNA, RNA, proteins, lipids and others causing various diseases such as cancer, arthritis, and heart diseases. 8-Hydroxyguanine (8-OHG) is one of the products formed from DNA or RNA damaged by ROS. Since high amounts of 8-OHG can be excreted in urine, it may serve as a potential biomarker indicating the level of oxidative damage to nucleic acids. Residents in industrial area with severe air pollution are expected to be affected by higher level of oxidative stress from pollutants like polyaromatic hydrocarbons (PAHs), etc. Smokers are also expected to be damaged by higher level of oxidative stress from cigarette smoke components like PAHs than non-smokers. To examine if the determination of the urinary concentration of 8-OHG could be used as exposure biomarker for the oxidative stress caused by air-pollutants, this study was performed to determine and compare the urinary concentrations of 8-OHG in smokers and non-smokers, or non-polluted area residents and polluted area residents. Urine samples were collected and purified by a strong cation exchange and cellulose partition column, then analyzed by HPLC with electrochemical detector at 600 ㎷ potential. Concentrations of urinary 8-OHG in non-smokers and smokers of Seoul area college male students were determined as 15.12$\pm$9.68 (ng/mg creatinine) and 34.72$\pm$11.72 (ng/mg creatinine), respectively, showing significantly higher level of 8-OHG in smokers than in non-smokers. Urine samples of elementary school students were collected from Sokcho area, which is known to be non-polluted, and 3 representative polluted areas; Yocheon industrial area, Ulsan urban and Ulsan industrial area. The concentrations of 8-OHG in these samples were 12.42$\pm$8.27 (ng/ mg creatinine, Sokcho), 22.55$\pm$9.12 (ng/mg creatinine, Yocheon), 17.41$\pm$2.30 (ng/mg creatinine, Ulsan urban), 55.04$\pm$39.73 (ng/mg creatinine, Ulsan industrial). Thus, samples from polluted area tend to have higher level of 8-OHG and the levels of Yocheon and Ulsan industrial area were significantly higher than that of Sokcho area. The results indicate that the residents of polluted industrial area or smokers are more severely exposed to oxidative stress probably caused by air pollutants like PAHs. Thus, the determination of urinary 8-OHG concentration could be used as biomarker for the extent of body exposure to oxidative stress caused by various pollutants.

• Biomolecules & Therapeutics
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• v.24 no.6
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• pp.604-609
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• 2016

5-fluorouracil (5-FU) is a chemotherapeutic agent commonly used for treatment of solid tumors, including colorectal cancer. However, chemoresistance against 5-fluorouracil (5-FU) often limits its success for chemotherapy and, therefore, finding out appropriate adjuvant(s) that might overcome chemoresistance against 5-FU bears a significant importance. In the present study, we have found that ${\alpha}$-mangostin can sensitize 5-FU-resistant SNUC5/5-FUR colon cancer cells to apoptosis. Exposure of ${\alpha}$-mangostin induced significant DNA damages and increased the intracellular 8-hydroxyguanosine (8-OH-G) and 4-hydroxynonenal (4-HNE) levels in SNUC5 and SNUC5/5-FUR cells. Western blot analysis illustrated that ${\alpha}$-mangostin-induced apoptosis was mediated by the activation of the extrinsic and intrinsic pathways in SNUC5/5-FUR cells. In particular, we observed that Fas receptor (FasR) level was lower in SNUC5/5-FUR cells, compared with SNUC5 cells and that silencing FasR attenuated ${\alpha}$-mangostin-mediated apoptosis in SNUC5/5-FUR cells. Together, our study illustrates that ${\alpha}$-mangostin might be an efficient apoptosis sensitizer that can overcome chemoresistance against 5-FU by activating apoptosis pathway.

• Journal of the Korean Society of Food Science and Nutrition
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• v.31 no.4
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• pp.672-678
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• 2002

Oxidative stress contributes to cellular injury following clinical and experimental ischemia/reperfusion scenarios. Oxidative injury can induce cellular and nuclear damages that result in apoptotic cell death. We tested the hypothesis that the catechin flavonoid of (-)epigallocatechin gallate, a green tea polyphenol, inhibits hydrogen peroxide ($H_2O$$_2$)-induced apoptosis in human umbilical vein endothelial cells. The effect of apigenin, a flavone found in citrus fruits, on apoptosis parameters was also examined. A 30 min pulse treatment with 0.25 mM $H_2O$$_2$ decreased endothelial cell viability within 24 hrs by > 30% ; this was associated with nuclear condensation and biochemical DNA damage consistent with programmed cell death. In the 0.25 mM $H_2O$$_2$apoptosis model, 50${\mu}{\textrm}{m}$ (-)epigallocatechin gallate markedly increased cell viability with a reduction in the nuclear condensation and DNA fragmentation. In contrast, equimicromolar apigenin increased cell loss with intense DNA laddering, positive nick-end labeling and Hoechst 33258 staining. Thus, polyphenolic (-)epigallocatechin gallate, but not apigenin flavone, qualify as an antioxidant in apoptosis models caused by oxidative stress. Further work is necessary for elucidating the anti-apoptotic mechanisms of polyphenolic catechins.

• The Journal of Korean Medicine
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• v.24 no.2
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• pp.179-192
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• 2003

Objectives : Boyanghwanoh-tang (Buyanhaiwu-tang) has been used as a prescription for stroke, senile and vascular dementia, ischemic brain and heart damage in Oriental traditional medicine. However, there is little known about the mechanism by which the water extracts of Boyanghwanoh-tang (Buyanhaiwu-tang) rescue cells fromthese damages, and little is known about the protective mechanisms of Boyanghwanoh-tang (Buyanhaiwu-tang) on oxidative stress in neuronal cells. Therefore, we have investigated the role of Boyanghwanoh-tang (Buyanhaiwu-tang) on serum and glucose deprived apoptosis in PC12 cells. Methods : PC12 Cells have been used extensively as a model for studying the cellular and molecular effects of neuronal cells. The viability of cells was measured by MIT assay. We used DNA fragmentation and caspase 1, 2, 3, 6, 9-likeproteases activation assay. Transcriptional activation of NF-kB was assessed by using electrophoretic mobility shift assay. Results : Boyanghwanoh-tang (Buyanhaiwu-tang) rescued PC12 cells from apoptotic death by serum and glucose deprivation in a dose-dependent manner. The nuclear staining of PC12 cells clearly showed that Boyanghwanoh-tang (Buyanhaiwu-tang) attenuated nuclear condensation and fragmentation, which represent typical neuronal apoptotic characteristics. Boyanghwanoh-tang (Buyanhaiwu-tang) also prevents fragmentation of genomic DNA and activation of caspase 3-like protease in serum and glucose deprived PC12 cells. Furthermore, Boyanghwanoh-tang (Buyanhaiwu-tang) reduced the activation of NF-kB by serum and glucose-deprived apoptosis. Conclusions : These findings suggest that serum and glucose deprivation induces reduced glutathione (GSH) depletion, and consequently, apoptosis through endogenously produced reactive oxygen species in PC12 cells. Also, our data indicated that Boyanghwanoh-tang (Buyanhaiwu-tang) has protective effects against the serum and glucose deprived deaths of PC12 cells, which are mediated by the generation of GSH that, in turn, can reduce oxidative stress caused by reactive oxygen species (ROS) such as hydrogen peroxide.