• Archives of Plastic Surgery
• /
• 제38권4호
• /
• pp.351-358
• /
• 2011

Purpose: The inflammatory phase is considered an integral part of adult wound healing, but fetal wound healing studies have shown scarless healing results in the absence of the inflammation process. The COX-2 pathway is an essential component of inflammation. The purpose of this study is to identify the effect of a topical selective COX-2 inhibitor on inflammation in rabbit skin wound healing and scarring. Methods: Full-thickness wounds were made on 6 New Zealand rabbits' ears. Topical 5% celecoxib + vehicle (experimental tissue) and vehicle only (controlled tissue) were applied daily for 14d on each side of the ears. Scar samples were harvested at 2 wks, 4 wks, and 8 wks after the wounding. Each sample was stained with hematoxylin and eosin and the Masson's trichrome stain to evaluate inflammation and scar formation. Results: Histological analysis demonstrated a significant reduction of inflammation, neovascularization, and scar elevation in the experimental tissue as compared to the control. Additionally, experimental tissue exhibited faster improvement of collagen organization similar to that of normal tissue. Conclusion: This study suggests that the topical application of a selective COX-2 inhibitor on a rabbit ear wound resulted in decreased inflammation and had a positive effect on the reduction of scar formation.

• Toxicological Research
• /
• 제35권1호
• /
• pp.83-91
• /
• 2019

Nanoparticles (NPs) have been recognized as both useful tools and potentially toxic materials in various industrial and medicinal fields. Previously, we found that zinc oxide (ZnO) NPs that are neurotoxic to human dopaminergic neuroblastoma SH-SY5Y cells are mediated by lipoxygenase (LOX), not cyclooxygenase-2 (COX-2). Here, we examined whether human bone marrow-derived mesenchymal stem cells (MSCs), which are different from neuroblastoma cells, might exhibit COX-2- and/or LOX-dependent cytotoxicity of ZnO NPs. Additionally, changes in annexin V expression, caspase-3/7 activity, and mitochondrial membrane potential (MMP) induced by ZnO NPs and ZnO were compared at 12 hr and 24 hr after exposure using flow cytometry. Cytotoxicity was measured based on lactate dehydrogenase activity and confirmed by trypan blue staining. Rescue studies were executed using zinc or iron chelators. ZnO NPs and ZnO showed similar dose-dependent and significant cytotoxic effects at concentrations ${\geq}15{\mu}g/mL$, in accordance with annexin V expression, caspase-3/7 activity, and MMP results. Human MSCs exhibited both COX-2 and LOX-mediated cytotoxicity after exposure to ZnO NPs, which was different from human neuroblastoma cells. Zinc and iron chelators significantly attenuated ZnO NPs-induced toxicity. Conclusively, these results suggest that ZnO NPs exhibit both COX-2- and LOX-mediated apoptosis by the participation of mitochondrial dysfunction in human MSC cultures.

• Journal of Hospice and Palliative Care
• /
• 제8권1호
• /
• pp.57-64
• /
• 2005

Cyclooxygenase-2 (COX-2) selective inhibitors were specifically developed to reduce the risks of gastrointestinal bleeding associated with other NSAID drugs. However, the APPROVe (Adenomatous Polyp Prevention on VIOXX) trials revealed that rofecoxib sometimes exerts prothrombotic effects. Meanwhile, cancer patients, who also carry a risk of thrombosis due to a variety of mechanisms, are often treated with COX-2 selective inhibitors, due to their relative gastrointestinal safety. This report concerns the case of a 46-year old woman with advanced cervical cancer, who had been treated with opioids and a COX-2 selective inhibitor (celecoxib) for 2 months, for the relief of pain associated with her cancer. The patient was admitted due to swelling of the left leg, which was also accompanied by pain. A computerized tomography scan revealed deep vein thrombosis occurring in multiple veins of both legs. After the administration of low-molecular weight heparin and oral warfarin, the patient's symptoms were relieved initially. However, her prothrombin time was found to be prolonged, necessitating the discontinuation of anticoagulation therapy. The patient's dyspnea worsened, ultimately resulting in her death. In conclusion, the administration of cox-2 selective inhibitors should be carefully considered in patients with a number of different risk factors, and assessed on a case-by-case basis.

• 한국응용약물학회:학술대회논문집
• /
• 한국응용약물학회 2001년도 추계학술대회 및 정기총회
• /
• pp.94-94
• /
• 2001

Prostaglandin endoperoxide H synthase (PGHS) catalyzes the committed step in prostaglandins and thromboxane A$_2$-- oxygenation of arachidonic acid to the hydroperoxy endoperoxide PGG$_2$, followed by reduction PGG$_2$to the alcohol PGH$_2$. The two reactions by PGHS -- cyclooxygenase and peroxidase -- occur at distinct but structurally and functionally interconnected sites. The peroxidase reaction occurs at a heme-containing active site located near the protein surface. The cyclooxygenase reaction occurs in a hydrophobic channel in the core of the enzyme. Initially a peroxide reacts with the heme group, yielding Compound I and an alcohol derived from the oxidizing peroxide. Compound I next undergoes an intramolecular reduction by a single electron traveling from Tyr385 along the peptide chain to the proximal heme ligand, His388, and finally to the heme group. Following the binding of arachidonic acid, Tyr385 tyrosyl radical initiates the cyclooxygenase reaction by abstracting the 13-pro(5) hydrogen atom to give an arachidonyl radical, which sequentially reacts with two molecules of oxygen to yield PGG$_2$. In order to characterize PGHS peroxidase active site, we examined various lipid peroxides with purified recombinant ovine PGHS proteins and determined the rate constants. The results have shown that twenty-carbon unsaturated fatty acid hydroperoxides have similar efficiency in peroxidation by PGHS, irrespective of either the location of hydroperoxy group or the number of double bonds. It was also confirmed by the subsequent study with PGHS peroxidase active site mutants.

• 대한화장품학회지
• /
• 제36권4호
• /
• pp.295-301
• /
• 2010

본 연구에서는 천연 추출물을 이용하여 화장품 원료를 개발하고자 다양한 천연물을 대상으로 조사하였고 그중 광나무 추출물을 선별하여 주름 개선 원료로 사용하고자 하였다. 고성능액체크로마토그래피를 수행하여 주름 개선 효과로 잘 알려진 oleanolic acid 31.06 %와 ursolic acid 8.92 %를 확인하였다. 제조된 광나무 추출물은 피부 섬유아세포에서 procollagen type I과 hyaluronan synthase-3의 발현을 증가시키고 matrix metalloproteinase (MMP)-1, MMP-2, cyclooxygenase-2의 발현을 감소시킬 뿐 아니라 elastase의 활성을 억제하여 주름 개선 기능을 갖는 것을 확인하였다. 따라서 광나무 추출물은 주름개선 화장품 소재로 개발될 수 있는 잠재력이 있다.

• 한국해양바이오학회지
• /
• 제1권3호
• /
• pp.193-197
• /
• 2006

별불가사리 단백추출물을 조제하여 유방암 발생 및 전이억제효과를 측정한 결과 종양세포증식에 관여하는 aromatase 활성이 농도의존적으로 억제효과가 있었으며, 침윤성 유방암에서 과발현하는 COX-2 단백질 발현을 억제하였다. 그리고 유방암이 진행될수록 활성이 증가하는 MMP-9도 농도의존적 저해율을 보였다. 그러므로 별불가사리 단백추출물은 유방암억제기전에 관련된 더 많은 연구를 통하여 유방암 예방물질로서 개발 가능성이 있는 것으로 보인다.

• Clinical and Experimental Reproductive Medicine
• /
• 제44권3호
• /
• pp.146-151
• /
• 2017

Objective: To identify differences in the expression of the genes for peroxisome proliferator-activated receptor $(PPAR)-{\gamma}$, cyclooxygenase (COX)-2, and the proinflammatory cytokines interleukin (IL)-6 and tumor necrosis factor $(TNF)-{\alpha}$ in granulosa cells (GCs) from polycystic ovary syndrome (PCOS) patients and controls undergoing controlled ovarian stimulation. Methods: Nine patients with PCOS and six controls were enrolled in this study. On the day of oocyte retrieval, GCs were collected from pooled follicular fluid. Total mRNA was extracted from GCs. Reverse transcription was performed and gene expression levels were quantified by realtime quantitative polymerase chain reaction. Results: There were no significant differences in age, body mass index, and total gonadotropin dose, except for the ratio of luteinizing hormone to follicle-stimulating hormone between the PCOS and control groups. $PPAR-{\gamma}$ and COX-2 mRNA was significantly downregulated in the GCs of PCOS women compared with controls (p= 0.034 and p= 0.018, respectively), but the expression of IL-6 and $TNF-{\alpha}$ mRNA did not show significant differences. No significant correlation was detected between the expression of these mRNA sequences and clinical characteristics, including the number of retrieved oocytes, oocyte maturity, cleavage, or the good embryo rate. Positive correlations were found among the $PPAR-{\gamma}$, COX-2, IL-6, and $TNF-{\alpha}$ mRNA levels. Conclusion: Our data may provide novel clues regarding ovarian GC dysfunction in PCOS, and indirectly provide evidence that the effect of $PPAR-{\gamma}$ agonists in PCOS might result from alterations in the ovarian follicular environment. Further studies with a larger sample size are required to confirm these proposals.

• 대한정형외과학회지
• /
• 제55권1호
• /
• pp.9-28
• /
• 2020

비스테로이드 소염제(non-steroidal anti-inflammatory drugs, NSAIDs)는 세계적으로 관절염과 같은 만성 통증에 가장 흔히 사용되는 약물이며 성분 및 기전에 따라 다양한 종류가 있다. 장기간 사용 시에는 소화기계 및 심혈관계 합병증 등의 다양한 부작용이 발생할 수 있는 것으로 알려져 있다. 기존의 비선택적 NSAID와 유사한 진통 효과를 지니면서 위장관계 내약성을 보완해줄 수 있는 cyclooxygenase-2 (COX-2) 선택적 NSAID가 많은 기대를 모았으나 2004년 및 2005년도에 심혈관계 안전성에 대한 우려로 rofecoxib과 valdecoxib의 허가가 취하되면서 NSAID 약물의 부작용에 관한 관심은 더욱 증가하고 있다. 따라서 각 약물의 부작용 및 상호작용을 고려하여 필요한 약물을 최소한으로 사용하는 것이 매우 중요하다. 본 논문에서는 NSAID 약물을 복용할 때 발생할 수 있는 부작용 및 각 약물의 특성을 숙지하며 비선택적 NSAID 및 COX-2 선택적 NSAID의 사용과 관련된 최근 연구 및 지침에 대해 알아보고자 한다.

• 생명과학회지
• /
• 제21권10호
• /
• pp.1494-1499
• /
• 2011

${\beta}$-lapachone은 남미에 자생하는 lapacho 나무(Tabeuia avellanedae)의 수액에 함유된 quinone계열의 일종으로 많은 인체암세포에서 apoptosis를 유발하는 것으로 알려져 있다. 본 연구는 A549 인체폐암세포를 대상으로 ${\beta}$-lapachone에 의한 apoptosis 유발 과정에서 나타나는 또 다른 현상들을 조사하기 위하여 실시되었다. ${\beta}$-lapachone이 처리된 A549 세포는 처리 농도의 증가에 따라 생존율이 감소되었으며, 이는 apoptosis 유발과 연관이 있음을 MTT assay와 flow cytometry 분석을 통하여 확인하였다. ${\beta}$-lapachone에 의한 A549 세포의 증식억제는 종양억제유전자 p53과 cyclin-dependent kinase 저해제인 p21의 발현을 전사 및 번역 수준에서 증가시켰으며, p53 단백질의 인산화 증가와 연관성이 있었다. 또한 ${\beta}$-lapachone은 caspase-3과 -9를 활성화시켰으며, 활성화된 caspase-3의 기질 단백질들[poly(ADP-ribose) polymerase, ${\beta}$-catenin 및 phospholipase C-$\gamma$1]의 단편화를 유도하였다. 아울러 ${\beta}$-lapachone은 cyclooxygenase (COX)-2의 mRNA 및 단백질의 발현을 억제하였으나 COX-1의 발현에는 영향을 미치지 않았으며, ${\beta}$-lapachone에 의한 COX-2의 발현억제는 prostaglandin E2의 생성 저하에 관련이 있었다. 본 연구의 결과는 ${\beta}$-lapachone의 항암활성 기전의 이해와 더불어 ${\beta}$-lapachone이 폐암세포에서 강력한 항암활성이 있음을 보여 주는 것이다.

• 생명과학회지
• /
• 제18권4호
• /
• pp.509-514
• /
• 2008

동 ${\cdot}$ 식물의 추출물은 예로부터 생약으로 많이 이용이 되었는데, 이는 추출물 내에 다양한 생리 활성 물질 및 화합물을 포함 하고 있기 때문이다. 본 연구는 한방에서 누고(樓姑)라고 알려진 땅강아지 추출물에 대한 항산화 활성을 1,1-diphenyl-2-picrylhydrazyl (DPPH)와 ferric reducing ability of plasma (FRAP)활성 실험을 통하여 알아보았다. 땅강아지는 DW, DMSO, 에탄올, 메탄올에 추출하였다. 실험 결과 땅강아지 추출물의 항산화활성은 DPPH radical 소거 활성의 경우 에탄올 추출물에서 가장 높은 활성을 나타났다. FRAP 활성의 경우 DW 추출물에서 가장 높게 나타났으며, 시간에 따른 활성의 증가는 에탄올 추출물에서 가장 높게 나타났다. Cyclooxygenase-2 promoter의 활성 저해는 DMSO와 에탄올 추출물에서 저해활성이 상대적으로 높은 것으로 미루어 보아서 이들 추출물간의 특성을 잘 응용할 경우 항산화 및 항염증에 좋은 생물학적 재료가 될 것으로 판단된다.