• 대한약리학회지
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• 제32권2호
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• pp.127-138
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• 1996

The effects of adenosine analogues on the electrically-evoked acetylcholine(ACh) release and the influence of ischemia on the effects were studied in the rat hippocampus. Slices from the rat hippocampus were equilibrated with $0.1{\mu}M$ $[^3H]-choline$ and the release of the labelled product, $[^3H]-ACh$, was evoked by electrical stimulation(3 Hz, 2 ms, 5 $VCm^{-1}$ and rectangular pulses for 2 min), and the influence of various agents on the evoked tritiumoutflow was investigated. Ischemia(10 min with 95% $N_2$ + 5% $CO_2$) increased both the basal and evoked ACh release. These increases were abolished by glucose addition into the superfused medium, and they significantly inhibited either by 0.1 & $0.3{\mu}M$ TTX pretreatment or by removing $Ca^{++}$ in the medium. MK-801($1{\sim}10{\mu}M$), a specific NMDA receptor antagonist, and glibenclamide $(1{\mu}M)$, a $K^+-channel$ inhibitor, did not alter the evoked ACh release and nor did they affect the ischemia-induced increases In ACh release. However, polymyxin B(0.03 mg), a specific protein kinase C inhibitor, significantly inhibited the effects of ischemia on the evoked ACh release. Adenosine and $N^6-cyclopentyladenosine$ decreased the ACh release in a dose dependent manner in ischemic condition, though the magnitude of inhibition was far less than those in normal(normoxic) condition. However, the treatment with $5{\mu}M$ DPCPX, a potent $A_1-adenosine$ receptor antagonist, potentiated the ischemia-effect. These results indicate that the evoked-ACh release is potentiated by ischemia, and this process being most probably mediated by protein kinase C, and that the decreased effect of ACh release mediated by $A_1-adenosine$ receptor is significantly inhibited in ischemic state.

• Journal of Preventive Medicine and Public Health
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• 제35권3호
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• pp.245-254
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• 2002

노인에서 $H_2$-RA의 복용과 위암간의 관련성을 밝히기 위한 코호트 내 환자-대조군 연구를 수행하였다. 연구 모집단은 공무원 및 사립학교 교직원을 대상으로 하는 의료보험 관리공단의 피보험자 및 피부양자로서 부산지역에 거주하는 65세 이상의 노인들을 대상으로 구축된 한국노인약물역학코호트의 구성원 중에서 교란변수에 대한 정보 획득을 위해 실시한 설문조사에서 응답한 사람들로 구성된 코호트이었다. $H_2$-RA폭로군은 1993년 1월 1일부터 1994년 12월 31일 사이에 코호트 대상자들이 병원에서 약물을 처방 받아 청구한 자료를 바탕으로 구축한 약물처방 데이터베이스에서 1회 이상 $H_2$-RA를 처방 받은 사람들도 정의하였다. 환자군 76명은 코호트의 위암 환자 확진을 위한 병원방문 조사 자료, 중앙 암등록 자료, 부산 지역 암등록 자료를 이용하여 확인되었다. 대조군은 환자군 확인방법과 동일한 방법을 이용하여 확인하였을 때 암으로 진단받은 병력이 없는 코호트 대상자들 중에서 환자군의 출생 년도와 성별에 따라 1:4의 비율로 개별 짝짓기를 실시하여 뽑은 304명이었다. 잠재적 인 교란변수에 대한 정보는 설문조사를 통해 수집하였다. 조건부 로지스틱 회귀모델을 이용하여 교란변수의 영향을 통제한 상태에서 구한 $H_2$-RA 복용과 위암 발생간의 관련성을 대응비와 95% 신뢰구간으로 제시하였다. 그 결과, 위궤양 증상 여부, 약물 복용력, 체질량 지수의 영향을 통제한 상태에서 $H_2$-RA의 복용은 위암 발생의 위험을 4.6배 증가시키는 것으로 관찰되었다. $H_2$-RA를 7일 이내로 사용한 군은 $H_2$-RA를 사용하지 않은 군에 비해 위암 발생의 위험이 4.6배 증가하는 것으로 관찰되었고 7일 이상 사용한 군은 2.3배 증가하는 것으로 관찰되었다. 투여 경로별로 나누어 보았을 때에는 경구로 투여한 경우에서 유의한 위험 수준의 상승을 관찰하지 못한 반면에 주사로 투여한 경우에서 위험이 4.4배 증가하는 것으로 관찰되었고, 주사와 경구의 두 가지 경로 모두로 $H_2$-RA를 투여 받은 경우 그 위험은 더욱 상승하는 것으로 관찰되었다.시메티딘, 라니티딘, 파모티딘 등의 개별 성분명 별로 위암 발생의 위험에 대한 차이는 관찰되지 않았다. 결론적으로 $H_2$-RA를 사용한 노인에서 사용하지 않은 노인에서 비해 위암 발생의 위험이 더 높아진다는 결론을 얻었으며, 이는 $H_2$-RA투여로 인해 위내에 발생한 무위산증(achlorhydria)이 위암 발생의 위험을 높일 것이라는 기존의 가설을 뒷받침하는 결론이라고 할 수 있었다.

• BMB Reports
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• 제53권5호
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• pp.284-289
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• 2020

Tamoxifen, a nonsteroidal estrogen receptor (ER) antagonist, is used routinely as a chemotherapeutic agent for ER-positive breast cancer. However, it is also causes side effects, including retinotoxicity. The retinal pigment epithelium (RPE) has been recognized as the primary target of tamoxifen-induced retinotoxicity. The RPE plays an essential physiological role in the normal functioning of the retina. Nonetheless, potential therapeutic agents to prevent tamoxifen-induced retinotoxicity in breast cancer patients have not been investigated. Here, we evaluated the action mechanisms of sulfasalazine against tamoxifen-induced RPE cell death. Tamoxifen induced reactive oxygen species (ROS)-mediated autophagic cell death and caspase-1-mediated pyroptosis in RPE cells. However, sulfasalazine reduced tamoxifen-induced total ROS and ROS-mediated autophagic RPE cell death. Also, mRNA levels of tamoxifen-induced pyroptosis-related genes, IL-1β, NLRP3, and procaspase-1, also decreased in the presence of sulfasalazine in RPE cells. Additionally, the mRNA levels of tamoxifen-induced AMD-related genes, such as complement factor I (CFI), complement factor H (CFH), apolipoprotein E (APOE), apolipoprotein J (APOJ), toll-like receptor 2 (TLR2) and toll-like receptor 4 (TLR4), were downregulated in RPE cells. Together, these data provide novel insight into the therapeutic effects of sulfasalazine against tamoxifen-induced RPE cell death.

• Archives of Pharmacal Research
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• 제25권5호
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• pp.697-703
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• 2002

We investigated that the role of nitric oxide (NO) on ischemic rats in brain and heart. Ischemia was induced by both common carotid arteries (CCA) occlusion for 24h following reperfusion. Then tissue samples were removed and measured NOx. In brain, NOx was increased by about 40% vs. normal and it was significantly inhibited by aminoguanidine, selective iNOS inhibitor. This result showed that NOx concentration was increased by iNOS. We investigated the role of $Ca^{2+}$ during ischemia. Nimodipine, L-type calcium channel blocker, didn't inhibit the increases of NOx concentration during ischemia. It suggested that increased NOx was due to calcium-independent NOS. MK-801, which N-methyl-D-aspartate (NMDA) receptor antagonist, didn't significantly prevent the increases of NOx. In heart, ischemia caused NOx decrease and it is inconsistent with NOx increase in brain. Aminoguanidine and nimodipine didnt affect on NOx decrease. But MK-801 more lowered NOx concentration than those of ischemia control group. It seemed that $Ca^{2+}$ influx in heart partially occurred via NMDA receptor and inhibited by NMDA receptor antagonist. The mean arterial pressure (MAP) in ischemic rats after 24h of CCA occlusion was decreased when compared to normal value, whereas the heart rates (HR) was not different between two groups. Aminoguanidine or MK801 had no effect on MAP or HR, but nimodipine reduced MAP. There was no difference the effects of aminoguanidine, nimodipine, or MK-801, on MAP and HR between normal rats and ischemic rats. In summary, ischemic model caused an increase of NOx concentration, suggesting that this may be produced via iNOS, which is calcium independent in brain. However in heart, ischemia decreased NOx concentration and NMDA receptor was partially involved. The basal MAP was decreased in ischemic rats but HR was not different from normal control, suggesting that increased NOx in brain of ischemic rat may result in the hypotension.

• 대한임상약리학회:학술대회논문집
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• 대한임상약리학회 2001년도 제10차 추계학술대회
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• pp.32-33
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• 2001

• Bulletin of the Korean Chemical Society
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• 제34권12호
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• pp.3851-3854
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• 2013

• Biomolecules & Therapeutics
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• 제25권2호
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• pp.202-212
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• 2017

Doxorubicin (DOX) is a highly effective chemotherapeutic agent; however, the dose-dependent cardiotoxicity associated with DOX significantly limits its clinical application. In the present study, we investigated whether Rb1 could prevent DOX-induced apoptosis in H9C2 cells via aryl hydrocarbon receptor (AhR). H9C2 cells were treated with various concentrations ($-{\mu}M$) of Rb1. AhR, CYP1A protein and mRNA expression were quantified with Western blot and real-time PCR analyses. We also evaluated the expression levels of caspase-3 to assess the anti-apoptotic effects of Rb1. Our results showed that Rb1 attenuated DOX-induced cardiomyocytes injury and apoptosis and reduced caspase-3 and caspase-8, but not caspase-9 activity in DOX-treated H9C2 cells. Meanwhile, pre-treatment with Rb1 decreased the expression of caspase-3 and PARP in the protein levels, with no effects on cytochrome c, Bax, and Bcl-2 in DOX-stimulated cells. Rb1 markedly decreased the CYP1A1 and CYP1A2 expression induced by DOX. Furthermore, transfection with AhR siRNA or pre-treatment with AhR antagonist CH-223191 significantly inhibited the ability of Rb1 to decrease the induction of CYP1A, as well as caspase-3 protein levels following stimulation with DOX. In conclusion, these findings indicate that AhR plays an important role in the protection of Ginsenoside Rb1 against DOX-triggered apoptosis of H9C2 cells.

• Advances in Traditional Medicine
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• 제9권2호
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• pp.135-141
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• 2009

The purpose of this study was to characterize the putative anxiolytic-like effects of the 70% ethanol extract of Portulaca oleracea (EPO) using an elevated plus maze (EPM) in mice. The EPO was orally administered at 50, 100, 200 or 400 mg/kg to ICR mice, 1 h before the behavioral evaluation in the EPM, respectively. Control mice were treated with an equal volume of 10% tween 80, and positive control mice with diazepam (1 mg/kg). Single treatments of the EPO significantly increased the percentage of time spent and arm entries into the open arms of the EPM versus controls (P < 0.05). Moreover, there were no changes in the locomotor activity and myorelaxant effects in any group compared with the saline controls. In addition, the anxiolytic-like effects of the EPO were blocked by flumazenil (10 mg/kg, i.p), a $GABA_A$ antagonist not by WAY 100635 (0.3 mg/kg, i.p), a 5-$HT_{1A}$ receptor antagonist. These results indicate that P. oleracea is an effective anxiolytic agent, and suggest that the anxiolytic-like effects of P. oleracea is mediated via the GABAergic nervous system.

• BMB Reports
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• 제49권9호
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• pp.520-525
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• 2016

We investigated the effects of two antimicrobial peptides (AMPs) isolated from Scolopendra subspinipes mutilans on neutrophil activity. Stimulation of mouse neutrophils with the two AMPs elicited chemotactic migration of the cells in a pertussis toxin-sensitive manner. The two AMPs also stimulated activation of ERK and Akt, which contribute to chemotactic migration of neutrophils. We found that AMP-stimulated neutrophil chemotaxis was blocked by a formyl peptide receptor (FPR) 1 antagonist (cyclosporin H); moreover the two AMPs stimulated the chemotactic migration of FPR1-expressing RBL-2H3 cells but not of vector-expressing RBL-2H3 cells. We also found that the two AMPs stimulate neutrophil migration in vivo, and that this effect is blocked in FPR1-deficient mice. Taken together, our results suggest that the two AMPs stimulate neutrophils, leading to chemotactic migration through FPR1, and the two AMPs will be useful for the study of FPR1 signaling and neutrophil activation.

• The Korean Journal of Pain
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• 제34권1호
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• pp.35-46
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• 2021

Background: The present investigation explored the therapeutic actions of oleuropein along with the possible signaling pathway involved in attenuating neuropathic pain in chronic constriction injury (CCI) and vincristine-induced neuropathic pain in male rats. Methods: Four loose ligatures were placed around the sciatic nerve to induce CCI, and vincristine (50 ㎍/kg) was injected for 10 days to develop neuropathic pain. The development of cold allodynia, mechanical allodynia, and mechanical hyperalgesia was assessed using different pain-related behavioral tests. The levels of H2S, cystathionine-γ-lyase (CSE), cystathionine-β-synthase (CBS), orexin, and nuclear factor erythroid-2-related factor 2 (Nrf2) were measured in the sciatic nerve. Results: Treatment with oleuropein for 14 days led to significant amelioration of behavioral manifestations of neuropathic pain in two pain models. Moreover, oleuropein restored both CCI and vincristine-induced decreases in H2S, CSE, CBS, orexin, and Nrf2 levels. Co-administration of suvorexant, an orexin receptor antagonist, significantly counteracted the pain-attenuating actions of oleuropein and Nrf2 levels without modulating H2S, CSE and CBS. Conclusions: Oleuropein has therapeutic potential to attenuate the pain manifestations in CCI and vincristine-induced neuropathic pain, possibly by restoring the CSE, CBS, and H2S, which may subsequently increase the expression of orexin and Nrf2 to ameliorate behavioral manifestations of pain.