• 한국환경독성학회:학술대회논문집
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• 한국환경독성학회 2003년도 추계국제학술대회
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• pp.13-13
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• 2003

Methylmercury (MeHg) is a ubiquitous environmental toxicant that can be exposed to humans by ingestion of contaminated food including fish and bread. MeHg has been suggested to exert its toxicity through its high reactivity to thiols, generation of arachidonic acid and reactive oxygen species (ROS), and elevation of intracellular $Ca^{2+}$ levels (［$Ca^{2+}$］$_{i}$). However, the precise mechanism has not been fully defined. Here we show that phosphatidylcholine-specific phospholipase C (PC-PLC) is a critical pathway for MeHg-induced toxicity. MeHg activated the acidic form of sphingomyelinase (A-SMase) and group IV cytosolic phospholipase $A_2$ ($cPLA_2$) downstream of PC-PLC, but these enzymes as well as protein kinase C were not linked to MeHg's toxicity. Furthermore, MeHg produced ROS, which did not cause the toxicity. However, D6O9, an inhibitor of PC-PLC, significantly reversed the toxicity in a time- and dose-dependent manner in MDCK and SH-5YSY cells. Addition of EGTA to culture media resulted in partial decrease of [$Ca^{2+}$］$_{i}$ and partially blocked cell death. In contrast, D609 completely prevented cell death with parallel decreases in diacylglycerol and ［$Ca^{2+}$］$_{i}$. Together, our findings indicated that MeHg-induced toxicity was caused by elevation of ［$Ca^{2+}$]$_{i}$ through activation of PC-PLC. The toxicity was not attributable to the signaling pathways such as $cPLA_2$, A-SMase, and PKC, or to the generation of ROS.

• 대한임상독성학회지
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• 제17권2호
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• pp.102-107
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• 2019

Purpose: Acute carbon monoxide (CO) poisoning is one of the most common types of poisoning and a major health problem worldwide. Treatment options are limited to normobaric oxygen therapy, administered using a non-rebreather face mask or hyperbaric oxygen. Compared to conventional oxygen therapy, high-flow nasal cannula oxygen (HFNC) creates a positive pressure effect through high-flow rates. The purpose of this human pilot study is to determine the effects of HFNC on the rate of CO clearance from the blood, in patients with mild to moderate CO poisoning. Methods: CO-poisoned patients were administered 100% oxygen from HFNC (flow of 60 L/min). The fraction of COHb (fCOHb) was measured at 30-min intervals until it decreased to under 10%, and the half-life time of fCOHb (fCOHb t_1/2) was subsequently determined. Results: At the time of ED arrival, a total of 10 patients had fCOHb levels ≥10%, with 4 patients ranging between 10% and 50%. The mean rate of fCOHb elimination patterns exhibits logarithmic growth curves that initially increase quickly with time (HFNC equation, Y=0.3388*X+11.67). The mean fCOHbt_1/2 in the HFNC group was determined to be 48.5±12.4 minutes. Conclusion: In patients with mild to moderate CO poisoning, oxygen delivered via high flow nasal cannula is a safe and comfortable method to treat acute CO toxicity, and is effective in reducing the COHb half-life. Our results indicate HFNC to be a promising alternative method of delivering oxygen for CO toxicity. Validating the effectiveness of this method will require larger studies with clinical outcomes.

• Toxicological Research
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• 제26권3호
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• pp.163-170
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• 2010

Cyclosporine A (CsA) is a potent immunosuppressor that is widely used in transplant surgery and the treatment of several autoimmune diseases. However, major side effects of CsA such as nephrotoxicity, hepatotoxicity, neurotoxicity and cardiovascular diseases have substantially limited its usage. Although molecular mechanisms underlying these adverse effects are not clearly understood, there is some evidence that suggests involvement of reactive oxygen species (ROS). In parallel, protective effects of various antioxidants have been demonstrated by many research groups. Extensive studies of CsA-induced nephrotoxcity have confirmed that the antioxidants can restore the damaged function and structure of kidney. Subsequently, there have appeared numerous reports to demonstrate the positive antioxidant effects on liver and other organ damages by CsA. It may be timely to review the ideas to envisage the relationship between ROS and the CsA-induced toxicity. This review is comprised of a brief description of the immunosuppressive action and the secondary effects of CsA, and a synopsis of reports regarding the antioxidant treatments against the ROS-linked CsA toxicity. A plethora of recent reports suggest that antioxidants can help reduce many CsA's adverse effects and therefore might help develop more effective CsA treatment regimens.

• Fisheries and Aquatic Sciences
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• 제18권1호
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• pp.35-44
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• 2015

We previously identified Streptomyces griseus as an anti-cancer agent (Kim et al., 2014). In this study, we isolated compounds from S. griseus and evaluated their anticancer effect and toxicity in vitro and in vivo. Preparative centrifugal partition chromatography (CPC) was used to obtain three compounds, cyclo($_{\small{L}}$-[4-hydroxyprolinyl]-$_{\small{L}}$-leucine], cyclo($_{\small{L}}$-Phe-trans-4-hydroxy-$_{\small{L}}$-Pro) and phenethyl acetate (PA). We chose PA, which had the highest anticancer activity, as a target compound for further experiments. PA induced the formation of apoptotic bodies, DNA fragmentation, DNA accumulation in $G_0/G_1$ phase, and reactive oxygen species (ROS) formation. Furthermore, PA treatment increased Bax/Bcl-xL expression, activated caspase-3, and cleaved poly-ADP-ribose polymerase (PARP) in HL-60 cells. Simultaneous evaluation in vitro and in vivo, revealed that PA exhibited no toxicity in Vero cells and zebrafish embryos. We revealed, for the first time, that PA generates ROS, and that this ROS accumulation induced the Bcl signaling pathway.

• 한국식품저장유통학회지
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• 제30권5호
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• pp.797-810
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• 2023

Elaeagnus umbellata leaves have been reported to suppress inflammation, allergic responses, lung cancer proliferation and oral bacterial growth. Cadmium (Cd) is a heavy metal that has been found to cause many toxicities, including liver toxicity. The aim of this study was to evaluate the capacity of 70% ethanol extract of E. umbellata leaves (EUL) to protect human hepatocytes from Cd toxicity. After exposure of HepG2 cells to Cd at 10 𝜇M for 24 h, cell viability, expression levels of apoptosis- and antioxidant-related proteins, reactive oxygen species (ROS) accumulation and Cd uptake were assessed. EUL protected HepG2 cells from Cd-induced apoptosis as determined by MTT assay. A decrease in caspase-3 and p-p53 protein levels was observed in cells pretreated with EUL prior to Cd exposure. Furthermore, the Cd-induced increase in intracellular DCF fluorescence was attenuated by EUL, indicating that the Cd-induced apoptosis preventing effect was associated with the suppression of ROS accumulation. Moreover, EUL's effects on the inhibition of p38, JNK, and AKT phosphorylation also appear to be associated with protection against Cd toxicity. Moreover, EUL upregulated Cd-depressed expression of Nrf2, HO-1, catalase, and MT-1,2 proteins, suggesting that Cd uptake-induced apoptosis in HepG2 cells may be inhibited by EUL's antioxidative potential.

• 한국수산과학회지
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• 제31권1호
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• pp.95-103
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• 1998

연안 및 천해에 서식하는 반부유성 갑각류인 곤쟁이, Neomysis awatschensis를 대상으로 수온별 PCB의 시험농도에 따른 생물검정, 성장, 호흡 및 질소배설 등을 측정하여 PCB의 영향으로 인한 생리적 변화를 알아보았다. 곤쟁이에 미치는 PCB의 96시간 후의 반수치사 농도 (96 hr.-$LC_50$)는 $10^{\circ}C$에서 28.7492ppb, $20^{\circ}C$에서는 10.6742 ppb였다. PCB의 만성농도에서 약 60일간 노출시킨 후 생존율은 $10^{\circ}C$의 경우, 0.5ppb에서 $85\%$, 1.0ppb에서 $80\%$ 였으며, 1.5ppb와 2.0ppb에서는 $75\%$를 나타내었으며, $20^{\circ}C$의 경우는 0.5ppb에서 $85\%$, 1.0ppb와 1.5ppb에서 $75\%$, 그리고 2.0ppb에서는 $65.0\%$를 나타내었다. PCB의 각 만성농도에 노출시킨 곤쟁이의 평균체장성장율은 $10^{\circ}C$의 경우 대조구의 경우 0.039mm10ay, PCB농도 2.0ppb에서는 0.036mm/day를 였으며, $20^{\circ}C$에서는 대조구에서 0.072mm/day, 2.0ppb에서 0.039mm/day를 나타내었다. PCB는 탈피간체장증가율에는 뚜렷한 영향을 미치지 않았으나 탈피기간에는 개체의 크기와 수온에 따라 영향을 나타내었다. 수온별 PCB의 각 실험농도에 노출시킨 곤쟁이의 호흡 및 질소배설량의 변화는 PCB 실험농도의 고수온구에서 높게 나타났다. 또한 섭이 및 동화효율은 $10^{\circ}C$와 $20^{\circ}C$에서 PCB농도의 증가에 따라 감소하는 경향을 나타내었다.

• 대한한방내과학회지
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• 제35권3호
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• pp.244-261
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• 2014

Objectives: This experiments were performed to determine the effects of the Jehasuogamibang (製何首烏加味方: JHGB) on antioxidationactivity and hyperlipidemia induced by a hypercholesterolemic diet in mice. Methods: After treatment with JHGB expert safety in cytotoxicity and toxicity of Human fibroblast cells and liver and kidney, effect on Reactive Oxygen Species, serum total cholesterol, LDL-cholesterol, triglyceride, glucose, HDL-cholesterol, lipid peroxid of liver tissue, significantly increased SOD and catalase. Results: 1. JHGB showed safety in cytotoxicity and toxicity of human fibroblast cells and liver and kidney. 2. JHGB showed significant inhibitory effect on reactive oxygen species. 3. JHGB significantly decreased serum total cholesterol, LDL-cholesterol, triglyceride, and glucose, and significantly increased serum HDL-cholesterol. 4. JHGB significantly decreased lipid peroxide of liver tissue and significantly increased SOD and catalase. Conclusions: These results suggest that Jehasuogamibang is effective in antioxidationactivity and dietary hyperlipidemia-induced mice.

• 한국토양비료학회지
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• 제50권4호
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• pp.203-214
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• 2017

Environmental toxicity due to cadmium (Cd) pollution in croplands causes critical problems worldwide. Rice (Oryza sativa L.) is an important crop in Asia, including South Korea, and numerous studies have evaluated the relationship between Cd and antioxidants to alleviate Cd uptake from the soil into plants. However, information about the relationship between phosphorus (P) and antioxidants in rice seedlings is still limited with regard to Cd phytotoxicity. We therefore investigated the physiological responses of rice (Oryza sativa L. cv 'Dongjin') seedlings to Cd toxicity and the effect of P application on reactive oxygen species (ROS) and antioxidant changes. The exposure of rice seedlings to $30{\mu}M$ Cd inhibited plant growth; increased the contents of superoxide, hydrogen peroxide, and malondialdehyde; and induced Cd uptake by the roots and leaves. Application of P to Cd-exposed seedlings decreased Cd-induced oxidative stress by enhancing the capacity of ascorbate (AsA) production and ROS-scavenging, and decreased Cd transfer from the roots to the leaves. These results suggest that P application alleviated Cd-induced growth inhibition and oxidative damage by restricting Cd translocation from the roots to the leaves and maintaining sufficient levels of AsA.

• Radiation Oncology Journal
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• 제32권3호
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• pp.103-115
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• 2014

To summarize current knowledge regarding mechanisms of radiation-induced normal tissue injury and medical countermeasures available to reduce its severity. Advances in radiation delivery using megavoltage and intensity-modulated radiation therapy have permitted delivery of higher doses of radiation to well-defined tumor target tissues. Injury to critical normal tissues and organs, however, poses substantial risks in the curative treatment of cancers, especially when radiation is administered in combination with chemotherapy. The principal pathogenesis is initiated by depletion of tissue stem cells and progenitor cells and damage to vascular endothelial microvessels. Emerging concepts of radiation-induced normal tissue toxicity suggest that the recovery and repopulation of stromal stem cells remain chronically impaired by long-lived free radicals, reactive oxygen species, and pro-inflammatory cytokines/chemokines resulting in progressive damage after radiation exposure. Better understanding the mechanisms mediating interactions among excessive generation of reactive oxygen species, production of pro-inflammatory cytokines and activated macrophages, and role of bone marrow-derived progenitor and stem cells may provide novel insight on the pathogenesis of radiation-induced injury of tissues. Further understanding the molecular signaling pathways of cytokines and chemokines would reveal novel targets for protecting or mitigating radiation injury of tissues and organs.

• 한국화재소방학회논문지
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• 제19권1호
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• pp.51-58
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• 2005

본 연구는 새로 개발된 난연도료를 바탕재(FRP PVC, AL, 스테인레스 스틸)에 도장한 실험체에 대하여 난연성. 화염전파. 산소지수. 가연성, 연기밀도, 독성지수를 평가하였다 연구결과 실험체(AL, 스테인레스 스틸)의 난연1급실험은 적합하였으며, 실험체(FRP, AL, 스테인레스 스틸)의 화염전파실험에서 착화되지 않았고, 실험체 모두의 산소지수는 약 $50\%$, 가연성실험은 V-0급으로 나타났다. 또한 연기밀도 챔버를 이용한 Flaming mode에서 최대연기밀도는 43-338 및 덕성지수는 0.57-1.12인 것으로 나타났다.