• Toxicological Research
• /
• 제31권4호
• /
• pp.347-354
• /
• 2015

Excess manganese (Mn) is neurotoxic. Increased manganese stores in the brain are associated with a number of behavioral problems, including motor dysfunction, memory loss and psychiatric disorders. We previously showed that the transport and neurotoxicity of manganese after intranasal instillation of the metal are altered in Hfe-deficient mice, a mouse model of the iron overload disorder hereditary hemochromatosis (HH). However, it is not fully understood whether loss of Hfe function modifies Mn neurotoxicity after ingestion. To investigate the role of Hfe in oral Mn toxicity, we exposed Hfe-knockout ($Hfe^{-/-}$) and their control wild-type ($Hfe^{+/+}$) mice to $MnCl_2$ in drinking water (5 mg/mL) for 5 weeks. Motor coordination and spatial memory capacity were determined by the rotarod test and the Barnes maze test, respectively. Brain and liver metal levels were analyzed by inductively coupled plasma mass spectrometry. Compared with the water-drinking group, mice drinking Mn significantly increased Mn concentrations in the liver and brain of both genotypes. Mn exposure decreased iron levels in the liver, but not in the brain. Neither Mn nor Hfe deficiency altered tissue concentrations of copper or zinc. The rotarod test showed that Mn exposure decreased motor skills in $Hfe^{+/+}$ mice, but not in $Hfe^{-/-}$ mice (p = 0.023). In the Barns maze test, latency to find the target hole was not altered in Mn-exposed $Hfe^{+/+}$ compared with water-drinking $Hfe^{+/+}$ mice. However, Mn-exposed $Hfe^{-/-}$ mice spent more time to find the target hole than Mn-drinking $Hfe^{+/+}$ mice (p = 0.028). These data indicate that loss of Hfe function impairs spatial memory upon Mn exposure in drinking water. Our results suggest that individuals with hemochromatosis could be more vulnerable to memory deficits induced by Mn ingestion from our environment. The pathophysiological role of HFE in manganese neurotoxicity should be carefully examined in patients with HFE-associated hemochromatosis and other iron overload disorders.

• Toxicological Research
• /
• 제31권1호
• /
• pp.17-23
• /
• 2015

Excessive manganese (Mn) in the brain promotes a variety of abnormal behaviors, including memory deficits, decreased motor skills and psychotic behavior resembling Parkinson's disease. Hereditary hemochromatosis (HH) is a prevalent genetic iron overload disorder worldwide. Dysfunction in HFE gene is the major cause of HH. Our previous study has demonstrated that olfactory Mn uptake is altered by HFE deficiency, suggesting that loss of HFE function could alter manganese-associated neurotoxicity. To test this hypothesis, Hfe-knockout ($Hfe^{-/-}$) and wild-type ($Hfe^{+/+}$) mice were intranasally-instilled with manganese chloride ($MnCl_2$ 5 mg/kg) or water daily for 3 weeks and examined for memory function. Olfactory Mn diminished both short-term recognition and spatial memory in $Hfe^{+/+}$ mice, as examined by novel object recognition task and Barnes maze test, respectively. Interestingly, $Hfe^{-/-}$ mice did not show impaired recognition memory caused by Mn exposure, suggesting a potential protective effect of Hfe deficiency against Mn-induced memory deficits. Since many of the neurotoxic effects of manganese are thought to result from increased oxidative stress, we quantified activities of anti-oxidant enzymes in the prefrontal cortex (PFC). Mn instillation decreased superoxide dismutase 1 (SOD1) activity in $Hfe^{+/+}$ mice, but not in $Hfe^{-/-}$ mice. In addition, Hfe deficiency up-regulated SOD1 and glutathione peroxidase activities. These results suggest a beneficial role of Hfe deficiency in attenuating Mn-induced oxidative stress in the PFC. Furthermore, Mn exposure reduced nicotinic acetylcholine receptor levels in the PFC, indicating that blunted acetylcholine signaling could contribute to impaired memory associated with intranasal manganese. Together, our model suggests that disrupted cholinergic system in the brain is involved in airborne Mn-induced memory deficits and loss of HFE function could in part prevent memory loss via a potential up-regulation of anti-oxidant enzymes in the PFC.

• Nuclear Engineering and Technology
• /
• 제54권1호
• /
• pp.110-116
• /
• 2022

Human failure event (HFE) dependency analysis is a part of human reliability analysis (HRA). For efficient HFE dependency analysis, a maximum number of minimal cut sets (MCSs) that have HFE combinations are generated from the fault trees for the probabilistic safety assessment (PSA) of nuclear power plants (NPPs). After collecting potential HFE combinations, dependency levels of subsequent HFEs on the preceding HFEs in each MCS are analyzed and assigned as conditional probabilities. Then, HFE recovery is performed to reflect these conditional probabilities in MCSs by modifying MCSs. Inappropriate HFE dependency analysis and HFE recovery might lead to an inaccurate core damage frequency (CDF). Using the above process, HFE recovery is performed on MCSs that are generated with a non-zero truncation limit, where many MCSs that have HFE combinations are truncated. As a result, the resultant CDF might be underestimated. In this paper, a new method is suggested to incorporate HFE recovery into the MCS generation stage. Compared to the current approach with a separate HFE recovery after MCS generation, this new method can (1) reduce the total time and burden for MCS generation and HFE recovery, (2) prevent the truncation of MCSs that have dependent HFEs, and (3) avoid CDF underestimation. This new method is a simple but very effective means of performing MCS generation and HFE recovery simultaneously and improving CDF accuracy. The effectiveness and strength of the new method are clearly demonstrated and discussed with fault trees and HFE combinations that have joint probabilities.

• Toxicological Research
• /
• 제30권4호
• /
• pp.267-276
• /
• 2014

Exposures to lead (Pb) are associated with neurological problems including psychiatric disorders and impaired learning and memory. Pb can be absorbed by iron transporters, which are up-regulated in hereditary hemochromatosis, an iron overload disorder in which increased iron deposition in various parenchymal organs promote metal-induced oxidative damage. While dysfunction in HFE (High Fe) gene is the major cause of hemochromatosis, the transport and toxicity of Pb in Hfe-related hemochromatosis are largely unknown. To elucidate the relationship between HFE gene dysfunction and Pb absorption, H67D knock-in Hfe-mutant and wild-type mice were given drinking water containing Pb 1.6 mg/ml ad libitum for 6 weeks and examined for behavioral phenotypes using the nestlet-shredding and marble-burying tests. Latency to nestlet-shredding in Pb-treated wild-type mice was prolonged compared with non-exposed wild-types (p < 0.001), whereas Pb exposure did not alter shredding latency in Hfe-mutant mice. In the marble-burying test, Hfe-mutant mice showed an increased number of marbles buried compared with wild-type mice (p = 0.002), indicating more repetitive behavior upon Hfe mutation. Importantly, Pb-exposed wild-type mice buried more marbles than non-exposed wild-types, whereas the number of marbles buried by Hfe-mutant mice did not change whether or not exposed to Pb. These results suggest that Hfe mutation could normalize Pb-induced behavioral alteration. To explore the mechanism of repetitive behavior caused by Pb, western blot analysis was conducted for proteins involved in brain dopamine metabolism. The levels of tyrosine hydroxylase and dopamine transporter increased upon Pb exposure in both genotypes, whereas Hfe-mutant mice displayed down-regulation of the dopamine transporter and dopamine D1 receptor with D2 receptor elevated. Taken together, our data support the idea that both Pb exposure and Hfe mutation increase repetitive behavior in mice and further suggest that these behavioral changes could be associated with altered dopaminergic neurotransmission, providing a therapeutic basis for psychiatric disorders caused by Pb toxicity.

• Nutrition Research and Practice
• /
• 제10권3호
• /
• pp.265-273
• /
• 2016

BACKGROUND/OBJECTIVES: The inhibitory effect of Hijikia fusiforme (HF) extracts on degenerative osteoarthritis was examined in primary cultured rat cartilage cells and a monosodium iodoacetate (MIA)-induced osteoarthritis rat model. MATERIALS/METHODS: In vitro, cell survival and the expression of matrix metalloproteinases (MMPs), collagen type I, collagen type II, aggrecan, and tissue inhibitor of metalloproteinases (TIMPs) was measured after $H_2O_2$ ($800{\mu}M$, 2 hr) treatment in primary chondrocytes. In vivo animal study, osteoarthritis was induced by intra-articular injection of MIA into knee joints of rats, and then RH500, HFE250 and HFE500 were administered orally once a day for 28 days. To determine the anti-inflammatory effects of HFE, nitric oxide (NO), prostaglandin $E_2$ ($PGE_2$) expression were measured. In addition, real-time PCR was performed to measure the genetic expression of MMPs, collagen type I, collagen type II, aggrecan, and TIMPs. RESULTS: In the in vitro assay, cell survival after $H_2O_2$ treatment was increased by HFE extract (20% EtOH). In addition, anabolic factors (genetic expression of collagen type I, II, and aggrecan) were increased by HFE extract (20% EtOH). However, the genetic expression of MMP-3 and 7, known as catabolic factors were significantly inhibited by treatment with HFE extract (20% EtOH). In the in vivo assay, anabolic factors (genetic expression of collagen type I, II, aggrecan, and TIMPs) were increased by oral administration of HFE extract. However, the genetic expression of MMP-3 and 7, known as catabolic factors, and production of NO and $PGE_2$ were significantly inhibited by treatment with oral administration of HFE extract. CONCLUSION: HFE extract inhibited articular cartilage degeneration through preventing extracellular matrix degradation and chondrocyte injury.

• 청정기술
• /
• 제14권3호
• /
• pp.184-192
• /
• 2008

불소계 화합물인 삼불화에탄올(2,2,2-trifluoroethanol, TFEA)와 수소화불화에테르(hydrofluoroether, HFE)는 성층권의 오존층을 파괴하지 않으며, 수소화불화탄소(hydrofluorocarbon, HFC) 및 수소화염화불화 탄소(hydrochlorofluorocarbon, HCFC)계 세정제에 비하여 지구온난화 영향력도 낮다. 특히, 인화점이 없는 HFE계 세정제는 낮은 인화점을 갖는 탄화수소계 세정제보다 취급에 안전하고 침투력이 우수하여 차세대 염화불화탄소(chlorofluorocarbon, CFC) 대체세정제로 주목받고 있다. 본 연구에서는 불소계 세정제인 TFEL HFE-7100, HFE-7200, HFE-476mec, HFE-449mec-f, AE-3000, AE-3100E와 실리콘계 세정제인 트리플 루로에톡시트리메틸실란(trifluoroetoxytrimethylsilane, TFES)와 헥사메틸디실라잔 (hexamethyldisilazane, HMDS)의 물성과 세정력을 오존파괴 물질인 CFC-113, 삼염화에탄(1,1,1-trichloroethane)와 유해물질인 이염화탄소(methylene chloride, MC) 등의 염소계 세정제, 그리고 현재 대체세정제로 많이 사용하고 있는 이소프로필알코올(isopropyl alcohol, IPA) 등과 비교 평가하였다. 그 결과 TFEA와 HFEs는 일반적으로 발생하는 다양한 오염물질들에 대하여 염소계 세정제에 비하여 낮은 세정능력을 보여주었지만, 불소를 함유한 불소계 오염물의 제거에는 우수한 세정력을 보였다. 그리고 실리콘계 세정제인 TFES와 HMDS도 실리콘계 오염물에 대한 세정력이 우수함을 보여주었다.

• 청정기술
• /
• 제16권3호
• /
• pp.172-181
• /
• 2010

CFC 세정제의 제3 세대 대체세정제로 평가되는 수소불화에테르(hydrofluoroether; HFE)는 불소분자를 함유하고 있어 표면장력이 낮고 습윤지수가 커서 미세입자제거와 불소계 오염물 제거에 우수하고 인화점이 없고 건조성이 뛰어난 물성을 가지고 있지만, 유기물의 용해력은 떨어져 유기 오염물 제거에는 효율적이지 못하다. 본 연구에서는 $C_5$계 HFE인 HFE-7100 [$CF_3CF_2CF_2CF_2OCH_3$]와 HFE-mec-f[$CF_3CHF=CF_2OCH_2CF_3$]에 유기물질의 용해력이 비교적으로 뛰어난 isopropyl alcohol (IPA), ethyleneglycol monoether (EG), propyleneglycol monoethylether (PM)를 인화점이 나타나지 않는 최대량을 각각 첨가하여 $C_5$계 HFE 기반의 배합세정제를 제조하여 물성과 여러 종류의 플럭스, 비수용성 절삭유, 불소계 오일에 대한 세정성 평가를 수행하였다. 실험 결과 $C_5$계 기반의 배합세정제는 단일 불소계 세정제의 여러 가지 물리적 성질의 장점을 가지는 것으로 나타났다. 그리고 $C_5$계 기반의 배합세정제는 첨가된 용제에 따라 약간의 차이는 있지만 대체적으로 플럭스, 비수용성 절삭유, 불소계 오일에 우수한 세정력을 나타내어 여러 산업세정 분야에 적용가능성을 보여주었다.

• 한국원자력학회:학술대회논문집
• /
• 한국원자력학회 2004년도 추계학술발표회 발표논문집
• /
• pp.599-600
• /
• 2004

• 한국원자력학회:학술대회논문집
• /
• 한국원자력학회 2005년도 춘계학술발표회
• /
• pp.1265-1266
• /
• 2005

• 대한화학회지
• /
• 제34권6호
• /
• pp.641-645
• /
• 1990

에탄올성 사카르보닐 철산염, HFe(CO)$_4^-$와 수용성 숙신알데히드를 조합하면 아미노기를 피롤리딘 고리로 선택적 전환을 하는데 매우 효과적이다. 페닐렌디아민은 일산화탄소 압력, 실온, 철산염존재하에서 숙신알데히드와 반응해서 대응하는 피롤리딘을 보통의 수득률로 주었다. 이 반응에 철산염-숙신알데히드-페닐렌디아민계에서 몰비가 1.0:1.0:1.0일 때는 1개의 피롤리딘고리를, 1.0:2.0:1.0의 경우는 두개의 피롤리딘 고리를 선택적으로 주었다.