• Toxicological Research
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• 제23권3호
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• pp.279-287
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• 2007

Copper (Cu) is an essential trace element indispensable for brain development and function; either excess or deficiency in Cu can cause brain malfunction. While it is known that Cu and Fe homeostasis are strictly regulated in the brain, the question as to how systemic Fe status may influence brain Cu distribution was poorly understood. This study was designed to test the hypothesis that dietary Fe condition affects Cu transport into the brain, leading to an altered brain distribution of Cu. Rats were divided into 3 groups; an Fe-deficient (Fe-D) group which received an Fe-D diet ($3{\sim}5 mg$ Fe/kg), a control group that was fed with normal diet (35mg Fe/kg), and an Fe-overload group whose diet contained an Fe-O diet (20g carbonyl Fe/kg). Following a 4-week treatment, the concentration of Cu/Fe in serum, CSF (cerebrospinal fluid) and brain were determined by AAS, and the uptake rates of Cu into choroids plexus (CP), CSF, brain capillary and parenchyma were determined by an in situ brain perfusion, followed by capillary depletion. In Fe-D and Fe-O, serum Fe level decreased by 91% (p<0.01) and increased by 131% (p<0.01), respectively, in comparison to controls. Fe concentrations in all brain regions tested (frontal cortex, striatum, hippocampus, mid brain, and cerebellum) were lower than those of controls in Fe-D rats (p<0.05), but not changed in Fe-O rats. In Fe-D animals, serum and CSF Cu were not affected, while brain Cu levels in all tested regions (frontal cortex, striatum, hippocampus, mid brain, and cerebellum) were significantly increased (p<0.05). Likewise, the unidirectional transport rate constants $(K_{in})$ of Cu in CP, CSF, brain capillary and parenchyma were significantly increased (p<0.05) in the Fe-D rats. In contrast, with Fe-O, serum, CSF and brain Cu concentrations were significantly decreased as compared to controls (p<0.05). Cu transport was no significant change of Cu transport of serum in Fe-O rats. The mRNA levels of five Cu-related transporters were not affected by Fe status except DMT1 in the CP, which was increased in Fe-D and decreased in Fe-O. Our data suggest that Cu transport into brain and ensuing brain Cu levels are regulated by systemic Fe status. Fe deficiency appears to augment Cu transport by brain barriers, leading to an accumulation of Cu in brain parenchyma.

• 대한수의학회지
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• 제39권1호
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• pp.77-84
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• 1999

Anesthetic agents are useful in inducing the anesthesia for surgical operations and various biological experiments, but they can disturb the body homeostasis and cause the stress in animals. Much efforts have been directed on reducing such side effects of anesthesia. In this work, we measured the serum ACTH, corticosterone and glucose concentration in rabbits to compare the degree of stress induced by two commonly-used anesthetics, ketamine, xylazine, and the combination of xylazine and ketamine. 1. The anesthesia was induced in about 10 min in the rabbits treated with xyalzine, ketamine and xylazine-ketamine. The duration of complete loss of righting reflex were 12, 13 and 115 min in the groups treated with xylazine, ketamine and xylazine-ketamine, respectively. 2. Serum ACTH concentrations in all treatment groups were higher than those in control group. At 30 min after the administration of the drugs, serum ACTH levels in ketamine-treated group were significantly higher than those in control, xylazine- and xylazine-ketamine-treated groups. However, at 1, 2, 5 and 9 hours after the drug administration, serum ACTH levels in xylazine-treated-group were higher than those in control. 3. Serum corticosterone levels in xylazine- and xylazine-ketamine-treated groups were lower than those in control or ketamine-treated groups at 0.5 and 1 hour after the administration. However, at 5 and 9 hours after the administration, serum corticosterone levels in xylazine- and xylazine-ketamine-treated groups were significantly higher than those in ketamine-treated group or control. 4. Serum glucose levels transiently increased to 3 times of the pre-injection levels at 0.5 and 1 hours after the administration in xylazine or xylazine-ketamine-treated groin, but were not changed in control and ketamine-treated group. These results indicate that xylazine-induced stress lasts longer than ketamine-induced, suggesting that the difference in stress-related hormone levels during anesthesia could be due to the differences in modes of actions of individual drugs used and the depth of anesthesia.

• 환경생물
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• 제32권4호
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• pp.271-285
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• 2014

알루미늄은 폐광산 침출수, 산업폐수, 생활하수 등을 통해 수계로 유입되어 수생생물에 농축되고 독성을 유발할 수 있다. 최근 다양한 수생생물에서 알루미늄의 독성에 관한 보고가 증가하고 있지만 오염현황 및 생태독성에 대한 연구가 많이 이뤄지지 않았다. 본 소고에서는 수서무척추동물, 어류, 양서류에서 알루미늄의 독성자료를 고찰함으로써 잔류량 가이드라인 설정의 필요성과 알루미늄의 수생태독성 분석전략을 제언하고자 하였다. 다양한 형태의 알루미늄화합물이 수생동물에서 1차적으로 아가미기능을 방해하여 생존을 위협하고 세포독성, 유전독성, 산화적스트레스, 내분비계교란, 생식교란, 대사교란, 항상성교란 등의 독성효과가 있는 것으로 확인되었다. 특히, 산성조건에서 환경잔류농도 수준의 알루미늄 화합물은 어류에서 호르몬농도 변화를 유발하였다. 알루미늄은 산성 및 염기성 조건에서 용해도가 증가하기 때문에 국내의 폐광산 인근의 산성 수계 뿐 아니라 조류 대발생에 의해 pH가 상승하는 호수나 강에서도 알루미늄의 독성효과가 나타날 것으로 사료된다.

• 생명과학회지
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• 제27권7호
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• pp.826-833
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• 2017

대기의 이산화탄소의 농도 증가는 해양산성화와 지구온난화를 유발하는 것으로 알려져 있다. 해마는 해양생태계 및 수산자원생물로서 중요한 종으로 알려져 있지만, 최근 해양산성화로 인하여 개체수가 감소되고 있는 실정이다. 따라서 본 연구에서는 멸종 위기 종인 복해마(Hippocampus kuda)에 미치는 생리적 영향을 조사하기 위해서 사육수의 산성조건인 pH 6.0, 6.5, 7.0 및 자연해수(pH 8.0)의 환경에서 복해마(H. kuda)를 15일 동안 사육 후 체내 조성 변화 및 항산화 효소 활성 변화에 대하여 조사를 실시하였다. 복해마(H. kuda)의 크기 및 성장은 대조군인 pH 8.0을 제외한 실험군에서는 pH가 저하함에 따라 감소하는 경향을 나타내었다. 체내 조성성분인 회분, 조지방 및 조단백 또한 pH 저하에 따라 농도의존적으로 감소하는 것이 관찰되었다. SOD, CAT 및 GSH와 같은 항산화 효소의 분석 결과, SOD활성의 경우, pH 저하에 따라 농도의존적으로 감소하지만, 이와 상반되게 CAT 및 GSH에서는 pH저하에 따라 활성이 농도의존적으로 증가하는 결과가 나타내었다. 이것은 복해마(H. kuda)가 사육수의 pH 저하에 따른 체내 항상성을 유지하는 과정 중 스트레스가 야기되어 에너지 대사가 손상된 것으로 추정된다. 항산화효소는 일반적으로 산성화 스트레스에 민감하게 작용하는데 본 연구에서도 사육수의 pH 변화에 따라 항산화 효소작용이 유의하게 변화하였다. 이러한 결과로 복해마(H. kuda)에 있어서 산성화 노출을 통한 생리학적 스트레스가 항산화 반응 및 체내 성분과 성장을 저해하는 것으로 여겨진다.

• Maxillofacial Plastic and Reconstructive Surgery
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• 제40권
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• pp.44.1-44.17
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• 2018

Background: Coffee extract has been investigated by many authors, and many minor components of coffee are known, such as polyphenols, diterpenes (kahweol and cafestol), melanoidins, and trigonelline, to have anti-inflammatory, anti-oxidant, anti-angiogenic, anticancer, chemoprotective, and hepatoprotective effects. Therefore, it is necessary to know its pharmacological effect on hepatocytes which show the most active cellular regeneration in body. Methods: In order to determine whether coffee extract has a beneficial effect on the liver, 20 C57BL/6J mice were intraperitoneally injected once with dialyzed coffee extract (DCE)-2.5 (equivalent to 2.5 cups of coffee a day in man), DCE-5, or DCE-10, or normal saline (control), and then followed by histological observation and IP-HPLC (immunoprecipitation high performance liquid chromatography) over 24 h. Results: Mice treated with DCE-2.5 or DCE-5 showed markedly hypertrophic hepatocytes with eosinophilic cytoplasms, while those treated with DCE-10 showed slightly hypertrophic hepatocytes, which were well aligned in hepatic cords with increased sinusoidal spaces. DCE induced the upregulations of cellular proliferation, growth factor/RAS signaling, cellular protection, p53-mediated apoptosis, angiogenesis, and antioxidant and protection-related proteins, and the downregulations of NFkB signaling proteins, inflammatory proteins, and oncogenic proteins in mouse livers. These protein expression changes induced by DCE were usually limited to the range ± 10%, suggesting murine hepatocytes were safely reactive to DCE within the threshold of physiological homeostasis. DCE-2.5 and DCE-5 induced relatively mild dose-dependent changes in protein expressions for cellular regeneration and de novo angiogenesis as compared with non-treated controls, whereas DCE-10 induced fluctuations in protein expressions. Conclusion: These observations suggested that DCE-2.5 and DCE-5 were safer and more beneficial to murine hepatocytes than DCE-10. It was also found that murine hepatocytes treated with DCE showed mild p53-mediated apoptosis, followed by cellular proliferation and growth devoid of fibrosis signaling (as determined by IP-HPLC), and subsequently progressed to rapid cellular regeneration and wound healing in the absence of any inflammatory reaction based on histologic observations.

• 대한지역사회영양학회지
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• 제17권2호
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• pp.243-257
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• 2012

The purpose of this study was to evaluate pancreatic ${\beta}$-cell function of Korean adult and to examine the associations between ${\beta}$-cell function and nutrient intakes. Data were analyzed for 1,917 male and 2,885 female subjects older than 30 years using 'The Forth Korean National Health and Nutrition Survey in 2009'. We calculated HOMA ${\beta}$-cell (The homeostasis model assessment of ${\beta}$-cell function) using fasting glucose and fasting insulin for assessing ${\beta}$-cell function. Subjects were divided into HHG (High HOMA ${\beta}$-cell Group) or LHG (Low HOMA ${\beta}$-cell Group) according to median of HOMA ${\beta}$-cell, and then nutrient intakes were compared between two groups. In the entire study population, HHG showed lower percent of carbohydrate intakes (p < 0.05), and higher fat (p < 0.01), percent of fat (p < 0.05), vitamin A (p < 0.05), carotene (p < 0.05) and riboflavin (p < 0.05) intakes than LHG. In addition, levels of HOMA ${\beta}$-cell were negatively correlated with percent of carbohydrate (${\beta}$ = -0.040, p < 0.05), and positively correlated with percent of fat (${\beta}$ = 0.046, p < 0.01). The subjects were then divided into two subgroups according to body mass index values, either $23kg/m^2$ (under- and normal-weight) or ${\geq}23kg/m^2$ (over-weight and obese). Significant differences of some nutrients intakes and correlations with HOMA ${\beta}$-cell were observed only in under- and normal weight subjects, but not in over-weight and obese subjects. In conclusion, high carbohydrate, lower fat and lower vitamin intakes may be related with pancreatic ${\beta}$-cell dysfunction in under- and normal-weight Korean.

• 대한통합의학회지
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• 제11권4호
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• pp.73-82
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• 2023

Purpose : Cymbopogon citratus, also known as lemongrass, has widely spread around the world and its essential oil is usually applied in food, perfume, and other industrial purposes. In addition, C. citratus has also been used for the treatment of inflammation, digestive disorders, and diabetes in traditional medicine. In this study, the antioxidative activity of C. citratus ethanol extract (CCEE) was analyzed in RAW 264.7 cells through the induction of one of phase II enzymes, heme oxygenase (HO)-1 by nuclear factor-erythroid 2 p45-related factor (Nrf)2, mitogen-activated protein kinase (MAPK), and phosphoinositide 3-kinase (PI3K)/Akt. Methods : The antioxidative activity of CCEE against oxidative stress and its underlying molecular mechanisms were analyzed by the cell viability assay, intracellular reactive oxygen species (ROS) formation assay, and Western blot analysis in RAW 264.7 cells. Results : The results exhibited that CCEE potently attenuated tert-butyl hydroperoxide (t-BHP) induced intracellular ROS levels in a dose-dependent manner without any cytotoxicity. CCEE treatment significantly induced the expression of HO-1 which is known for its antioxidative capacity. In addition, CCEE treatment significantly upregulated the expression of Nrf2, a corresponding transcription factor for the regulation of antioxidative enzymes, which was in accordance with the HO-1 overexpression. MAPK and PI3K/Akt were also evaluated for their important roles in the regulation of cellular redox homeostasis against oxidative damage. As a result, the potent HO-1 expression was mediated by not extracellular regulated kinase (ERK), c-Jun NH2 terminal kinase (JNK), p38, but phosphoinositide 3-kinase (PI3K) phosphorylation. To confirm the antioxidative activity of CCEE-induced HO-1 expression, oxidative damage was initiated by t-BHP and attenuated by CCEE treatment, which was identified by HO-1 selective inhibitor and inducer. Conclusion : Consequently, CCEE potently induced the HO-1-mediated antioxidative potential through the modulation of Nrf2 and PI3K/Akt signaling pathways in RAW 264.7 cells. These results suggest that CCEE could be a promising strategy for the mitigation against cellular oxidative damage.

• Journal of Microbiology and Biotechnology
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• 제33권12호
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• pp.1635-1647
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• 2023

Muscle atrophy, which is defined as a decrease in muscle mass and strength, is caused by an imbalance between the anabolism and catabolism of muscle proteins. Thus, modulating the homeostasis between muscle protein synthesis and degradation represents an efficient treatment approach for this condition. In the present study, the protective effects against muscle atrophy of ethanol extracts of Morus alba L. (MA) and Angelica keiskei Koidz. (AK) leaves and their mixtures (MIX) were evaluated in vitro and in vivo. Our results showed that MIX increased 5-aminoimidazole-4-carboxamide ribonucleotide-induced C2C12 myotube thinning, and enhanced soleus and gastrocnemius muscle thickness compared to each extract alone in dexamethasone-induced muscle atrophy Sprague Dawley rats. In addition, although MA and AK substantially improved grip strength and histological changes for dexamethasone-induced muscle atrophy in vivo, the efficacy was superior in the MIX-treated group. Moreover, MIX further increased the expression levels of myogenic factors (MyoD and myogenin) and decreased the expression levels of E3 ubiquitin ligases (atrogin-1 and muscle-specific RING finger protein-1) in vitro and in vivo compared to the MA- and AK-alone treatment groups. Furthermore, MIX increased the levels of phosphorylated phosphoinositide 3-kinase (PI3K), protein kinase B (Akt), and mammalian target of rapamycin (mTOR) that were reduced by dexamethasone, and downregulated the expression of forkhead box O3 (FoxO3a) induced by dexamethasone. These results suggest that MIX has a protective effect against muscle atrophy by enhancing muscle protein anabolism through the activation of the PI3K/Akt/mTOR signaling pathway and attenuating catabolism through the inhibition of FoxO3a.

• 생명과학회지
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• 제28권3호
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• pp.284-292
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• 2018

멜라닌 농축 호르몬(melanin-concentrating hormone, MCH)은 17개의 아미노산으로 구성된 환형의 시상하부 펩티드로 색소 침착의 조절인자로서 연어에서 처음 분리되었다. 포유동물의 MCH는 19개의 아미노산으로 구성되어 있으며 섭식 및 에너지 항상성을 조절하는데 관여한다. 본 연구에서는 양식넙치의 다양한 조직에서 MCH 유전자의 발현 분포, 멜라닌 함유 세포의 집적, 포유동물 MCH 수용체와 양식넙치 MCH의 상호작용을 조사하였다. Real-time qPCR을 이용하여 뇌, 정소, 난소에서 MCH 유전자의 발현이 나타나는 것을 확인하였고, 수정 후 발달 단계에서도 MCH 유전자의 발현을 확인할 수 있었다. 합성된 연어 sMCH, 포유류 hMCH, 양식넙치 fMCH, dN-fMCH, dC-fMCH를 양식 넙치의 표피에 처리했을 때 다양한 농도에 따라 멜라닌 함유 세포의 집적이 다양하게 나타났다. 연어 sMCH, 포유류 hMCH에 비해 양식넙치 fMCH의 멜라닌 함유세포의 집적도가 36~99.85%로 비역가를 나타났으나 양식넙치 dN-fMCH, dC-fMCH를 처리한 경우 양식넙치 fMCH에 비해 높은 농도에서 집적이 나타나고 짧은 시간에 분산되었다. 또한, 인간 MCH 수용체와 쥐 MCH 수용체가 발현된 포유동물의 세포주에 양식넙치 fMCH를 처리하여 각 수용체와 결합하는 것을 확인하였다. 이러한 결과는 어류에서 발현되는 MCH가 포유동물의 MCH와 유사한 구조를 가지고 있어 MCH 수용체에 대한 새로운 리간드로서 제공될 수 있으며, 향후 어류의 MCH 수용체에 확대 적용할 수 있을 것이다.

• 생명과학회지
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• 제28권7호
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• pp.772-777
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• 2018

본 연구에서는 화본과 다년생 식물인 양초의 환경 스트레스에 대한 적응 기작을 이해하기 위해, 과산화수소를 제거하는 주요 항산화효소인 peroxidase (POD), ascorbate peroxidase (APX) 및 catalase (CAT) 활성의 변화를 고염과 건조 스트레스 조건에서 조사하였다. 300 mM 이상의 NaCl과 40% PEG 처리에서 양초 유식물체의 지상부와 지하부의 생장이 크게 감소하였다. 항산화효소 수준은 양초 유식물체의 지상부에서 CAT 활성이 높았지만, APX와 POD는 지하부에서 높은 활성 수준을 보였다. 실제로 NaCl과 PEG 처리동안 APX 활성은 지상부와 지하부가 모두 증가하였으며, CAT 활성은 지상부만 증가하였다. 또한 고염 조건에서 양초식물체의 지상부와 지하부 모두에서 전체페놀 함량이 증가하였다. 본 연구의 결과로서, 양초의 유식물체의 지상부 및 지하부의 생장이 과산화수소를 제거하는 항산화효소활성에 의해 조절됨을 알 수 있었으며, 이는 뿌리에서 APX 활성의 증가 및 지상부에서 CAT 활성증가와 같은 효소활성의 조직 특이적 증가에 영향을 받음을 알 수 있다. 본 연구의 결과는 전형적인 사막지역을 포함하는 고염 지역에서 양초 유식물체의 생장을 위해 항산화 방어기작이 중요함을 의미하는 바이다.