• Title/Summary/Keyword: oxygen toxicity

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Methylmercury Toxicity Is Induced by Elevation of Intracellular $Ca^{2+}$ through Activation of Phosphatidylcholine-Specific Phospholipase C

  • Chin, Mi-Reyoung;Kang, Mi-Sun;Jeong, Ju-Yeon;Jung, Sung-Yun;Seo, Ji-Heui;Kim, Dae-Kyong
    • Proceedings of the Korea Society of Environmental Toocicology Conference
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    • 2003.10a
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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.

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A Preliminary Study for Effect of High Flow Oxygen through Nasal Cannula Therapy in Carbon Monoxide Poisoning (일산화탄소 중독 환자에서 고유속 비강 캐뉼라 산소치료 효과에 대한 예비 연구)

  • Kim, Young-Min;Kim, Sang-Chul;Park, Kwan-Jin;Lee, Seok-Woo;Lee, Ji-Han;Kim, Hoon
    • Journal of The Korean Society of Clinical Toxicology
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    • v.17 no.2
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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 t1/2) 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 fCOHbt1/2 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.

Use of Antioxidants to Prevent Cyclosporine A Toxicity

  • Lee, Jin-Hwa
    • Toxicological Research
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    • v.26 no.3
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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.

Evaluation on Anticancer Effect Against HL-60 Cells and Toxicity in vitro and in vivo of the Phenethyl Acetate Isolated from a Marine Bacterium Streptomyces griseus

  • Lee, Ji-Hyeok;Zhang, Chao;Ko, Ju-Young;Lee, Jung-Suck;Jeon, You-Jin
    • Fisheries and Aquatic Sciences
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    • v.18 no.1
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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.

Efficacy of Elaeagnus umbellata leaves on prevention of cadmium-induced toxicity in HepG2 cells

  • Jae-Yeul Lee;Seun-Ah Yang;Won-Bin Bae
    • Food Science and Preservation
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    • v.30 no.5
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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.

Effects of PCBs (Polychlorinated Biphenyls) on Energy Budget in Mysid, Neomysis awatschensis I. Acute and Chronic Effects of PCBs on Mysid, Neomysis awatschensis (곤쟁이, Neomysis awatschensis의 에너지수지에 미치는 PCBs의 영향 I. 곤쟁이에 미치는 PCBs의 급성 및 만성영향)

  • CHIN Pyung;SHIN Yun-Kyung;JEON Eun-Mi
    • Korean Journal of Fisheries and Aquatic Sciences
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    • v.31 no.1
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    • pp.95-103
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    • 1998
  • Acute and chronic responses to PCB toxicity of Neomysis awatschensis were studied by measurement of bioassay, growth, oxygen consumption and nitrogen excretion with concentrations of PCB at 10 and $20^{\circ}C$. 96 hr.-$LC_50$ at 10 and $20^{\circ}C$ were 28.7492 pub and 10.6742 pub, respectively. Survival rates during 60 days exposured to chronic PCB concentrations of 0.5 pub, 1.0 pub, 1.5 pub and 2,0 pub at $10^{\circ}C$ were $85\%,\;80\%,\;75\%$ and $75\%$, respectively and suwival rates at $20^{\circ}C$ $85\%,\;75\%,\;75\%$ and $65\%$, respectively. Average daily growth rate of N. awatschensis exposed to chronic PCB concentrations at $10^{\circ}C$ were 0.039 mm/day in control group and 0.036 mm/day at concentration of 2.0 ppb, while their rates at $20^{\circ}C$ showed 0.072 mm/day in central group and 0.039 mm/day at 2,0 ppb. The growth factors were some similarities between the chronic PCB concentrations, but intermolt periods were related to body size of mysids, temperature and PCB toxicity. Changes in oxygen consumption and nitrogen excretion rates during 60 days exposure to PCB toxicity showed higher in high groups of PCB concentrations. Assimilation and feeding rates of N. awatschensis fed Artemia sp. decreased with increase of PCB concentration at 10 and $20^{\circ}C$.

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The Effects of Jehasuogamibang on Antioxidation Activity and Dietary Hyperlipidemia-induced Mice (제하수오가미방(製何首烏加味方)이 고지혈증 및 산화적 손상에 미치는 영향)

  • Youn, Hyeon-Deok;Jo, Hyun-Kyung;Yoo, Ho-Ryong;Seol, In-Chan;Kim, Yoon-Sik
    • The Journal of Internal Korean Medicine
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    • v.35 no.3
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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.

Effect of Phosphorus on the Cadmium Transfer and ROS-scavenging Capacity of Rice Seedlings

  • Jung, Ha-Il;Chae, Mi-Jin;Kong, Myung-Suk;Kim, Yoo-Hak
    • Korean Journal of Soil Science and Fertilizer
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    • v.50 no.4
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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.

Mechanisms of radiation-induced normal tissue toxicity and implications for future clinical trials

  • Kim, Jae Ho;Jenrow, Kenneth A.;Brown, Stephen L.
    • Radiation Oncology Journal
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    • v.32 no.3
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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.

A Fire Risk Assessment of Substrate for Fire Resistant Painted (난연도료를 도장한 바탕재의 화재 위험성평가)

  • Park Young-Keun;Lee Doo-Hyung;Yoon Myung-O;Hyun Seong-Ho
    • Fire Science and Engineering
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    • v.19 no.1 s.57
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    • pp.51-58
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    • 2005
  • In this paper, The experimental materials of painted fire resistant paint on substrate, FRP, PVC, AL and stainless steel that fire resistant paint developed newly were evaluated as the hazard elements : the fire resistibility of the materials, fire spread test of flame, the oxygen index, flammability, the smoke density. the toxicity index from it when it burned. As a result of the experiments, the AL and the stainless steel were passed of fire resistant class 1, the FRP, the AL, and the stainless steel were ignited of fire spread test of flame, all the experimental materials showed about $50\%$ of oxygen index, V-0 of flammability, and 43-338 of maximum smoke density at flaming mode used smoke density chamber. Also, they showed that the toxicity index of combustion products were 0.57-1.12.