• Tuberculosis and Respiratory Diseases
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• v.39 no.1
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• pp.42-54
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• 1992

Background:It has been suggested that the cyclooxygenase metabolites play an important role in changes of early hemodynamic parameters in the endotoxin-induced acute lung injury. But there have been many debates about their role in the late increase of alveolar-capillary permeability, and it is not known whether they act directly or indirectly through oxygen free radicals which have been known to be produced during the metabolic process of cyclooxygenase pathway. So we performed this study to identify the pathogenetic role of cyclooxygenase metabolites in the endotoxin-induced acute lung injury in domestic pigs. Method: We infused endotoxin into 8 domestic pigs; endotoxin only (n=3), and pretreatment with indomethacin (n=5). We observed the sequential changes in hemodynamic parameters, the concentration of plasma oxidized glutathione (GSSG) in pulmonary arterial and venous blood, and albumin content in bronchoalveolar lavage fluid (BALF). Results: 1) While cardiac output decreased, mean pulmonary arterial pressure, pulmonary vascular resistance, and alveolar-arterial oxygen difference increased over phase 1 (0-2hr) and phase 2 (2-4.5hr) by endotoxin, indomethacin attenuated the decrease in cardiac output during phase 1 and increase in mean pulmonary arterial pressure, pulmonary vascular resistance, and alveolar-arterial oxygen difference during both phases. 2) The increase in plasma GSSG content during phase 2 was not attenuated by indomethacin. 3) The content of BALF albumin was significantly lower in indomethacin groups than that of endotoxin group. Conclusion: These results suggest that it is likely that cyclooxygenase metabolites have an effect on endotoxin-induced acute lung injury during both phases probably through direct action.

• Journal of Yeungnam Medical Science
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• v.23 no.1
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• pp.36-44
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• 2006

Background: There is controversy regarding whether COX-2 specific inhibitors are associated with elevation of blood pressure. We compared the effects of aspirin, indomethacin, and celecoxib for vascular reactivity induced by phenylephrine. We also tested the effects of indomethacin and NO donor on COX-1 and COX-2 protein expression, as well as nitrite production in culture medium of vascular smooth muscle cells. Materials and Methods: In this experiment, we used the isometric tension study for vascular reactivity. After 45 minutes of pretreatment with aspirin, indomethacin, celecoxib, and phenylephrine induced contractions were tested. COX-1 and COX-2 protein expressions were analyzed by Western blot and nitrite production by the Griess reaction. Results: Although celecoxib pretreatment caused enhanced arterial contraction, aspirin pretreatment induced more potent arterial contraction than celecoxib in the isometric tension study of rabbit femoral artery. COX-1 protein expression was unchanged by indomethacin, SNP and NOR-3; COX-2 protein expression was increased by the addition of indomethacin, SNP, and NOR-3. Especially, NOR-3, a NO donor, significantly increased COX-2 protein expression with unstimulated conditions as well as LPS stimulation. Induction of nitrite production was higher with NOR-3 treatment than SNP treatment with LPS stimulation. Conclusion: These results suggest that aspirin caused more potent vascular contraction than celecoxib and indomethacin. COX-2 expression in VSMC depended on the types of NO donor and LPS stimulation.

• The Korean Journal of Pharmacology
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• v.29 no.2
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• pp.237-244
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• 1993

The effect of nicotine on the secretion of $[Met^{5}]-enkephalin$ (ME) in addition to proenkephalin A (proENK) mRNA levels and effects of indomethacin, nordihydroguaiaretic acid (NDGA), and captopril on nicotine-induced responses were studied in bovine adrenal medullary chromaffrin (BAMC) cells. Long-term exposure of BAMC cells to nicotine at a concentration of $10{\mu}M$ significantly increased proENK mRNA level and the secretion of ME into the medium. Treatment of BAMC cells with NDGA (a lipoxygenase inhibitor, $10{\mu}M$), indomethacin (a cycloooxygenase inhibitor) or captopril (an angiotensin converting enzyme inhibitor) alone did not affect ME secretion and proENK mRNA levels. The pretreatment of BAMC cells with NDGA inhibited the increased ME secretion and proENK mRNA level induced by nicotine. However, indomethacin and captopril did not affect nicotine-induced responses. Our results indicate that neuronal regulations of ME secretion and proENK mRNA level induced by nicotine in BAMC cells are in part mediated by a lipoxygenase-but not cyclooxygenase-and endogenous renin-angiotensin pathway.

• Journal of Physiology & Pathology in Korean Medicine
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• v.21 no.6
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• pp.1394-1400
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• 2007

This study was designed to investigate the effects of Samul-tang Extract and Bambusae caulis in liquamen(SEB) on the changes in regional cerebral blood flow (rCBF) and mean arterial blood pressure (MABP) in normal rats. The results were as follows ; SBE significantly increased rCBF in a dose-dependent manner, and increased MABP in a dose-dependent manner. This result suggests that SBE significantly increased rCBF by dilating pial arterial diameter. Increase of SBE-induced rCBF was significantly inhibited by pretreatment with indomethacin (1 mg/kg, i.p.), an inhibitor of cyclooxygenase and increase of SBE-induced rCBF was inhibited by pretreatment with methylene blue ($10\;{\mu}g/kg$, i.p.), an inhibitor of guanylate cyclase. Increase of SBE-induced MABP was significantly increased by pretreatment with methylene blue but increase of SBE-induced MABP was decreased by pretreatment with indomethacin. These results suggested that the action of SBE was mediated by cyclooxygenase.

• The Korean Journal of Physiology and Pharmacology
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• v.4 no.6
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• pp.525-530
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• 2000

During reperfusion of skeletal muscle after ischemia, lipid mediators, mainly eicosanoids, are released and may have a role in the pathogenesis of reperfusion injury. To validate the role of eicosanoids in the ischemia-reperfusion induced functional deficits in skeletal muscle, we compared muscle edema and the changes of eicosanoid concentration in the rat hind limb after ischemia-reperfusion injury by application of tourniquet. After 4 hours of ischemia, reperfusion was established for 4 hours by releasing tourniquet. To assess tissue damage, edema, and wet/dry weight ratios were determined and the eicosanoid concnentrations were measured by the HPLC. The muscle edema and the release of cyclooxygenase metabolites were not induced by the ischemia itself rather they were significantly increased by reperfusion. Indomethacin treatment ameliorated limb edema and decreased the release of $6-keto-PGF_{1{\alpha}},$ thromboxane $B_2,$ and $PGE_2$ inducedby reperfusion. But the inhibitory effect of indomethacin on edema (35%) was relatively low than the inhibitory effect on release of cyclooxygenase metabolites (up to 69%) by reperfusion. These results support the view that cyclooxygenase products may play a significant role in the formation of muscle injury by ischemia-reperfusion and suggest that nonsteroidal antiinflammatory agents might be partially beneficial to the management of acute limb ischemia-reperfusion injury.

• The korean journal of orthodontics
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• v.35 no.5 s.112
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• pp.351-360
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• 2005

This study aimed to investigate the effects of indomethacin on distribution and expression of COX-2 and IGF-1 in the mandibular condyle ofi growing dogs and to examine the number of chondroclasts around the mineralization zone indomethacin inhibits prostatlandin $E_2$ production in the tissue by inhibiting synthesis of cyclooxygenase 2. Prostaglandin $E_2$ stimulates insulin-like growth factor synthesis. Insulin-like growth factor stimulates growth of mandibular condylar cartilage. Eight mongrel dogs. aged 13-14 weeks, were divided into 4 groups. Group 1 and group 2 were administered indomethacin 2 mg/Kg/day orally two times a day for 7 days and 14 days respectively. Group 3 were administered indomethacin 8mg/Kg/day orally 2 times a day for 14 days, and 4he control group were administered a placebo. The mandibular condyle heads were sectioned in $5{\mu}m$ thickness The specimens were stained with H-E staining. COX-2 immunohistochemical staining and IGF-1 immunohistochemical staining and examined under microscope. After TRAP staining, the number of chondroclasts were calculated The observed results were as follows: Indomethacin inhibited expression and distribution of COX-2 and IGF-1 on the proliferative zone of condylar cartillage. Indomethacin decreased the number of chondroclastes on the mineralization zone by a time-dependent manner (P<0.05). Indomethacin inhibited expression and distribution of IGF-I by a dose and time-dependent manner. These results show that indomethacin inhibited expression and distribution of COX-2 and IGF-1 on the proliferative zone of condylar cartilage and decreased the number of chondroclasts and suggests that when indomethacin is administered for a long time, condyle growth could be delayed.

• The Journal of Internal Korean Medicine
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• v.34 no.4
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• pp.412-427
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• 2013

Objectives : This study was carried out to compare the effects of Eejin-tang, Hyangsaeejin-tang and Naeso-san extracts on indomethacin-induced gastric mucosal lesions in mice. Methods : Experimental mice were divided into six groups. The normal group had no gastro-inflammation. In the control group, gastro-inflammation was elicited by indomethacin. Misoprostol, Eejin-tang, Hyangsaeejin-tang and Naeso-san group were those in which misoprostol, Eejin-tang extract, Hyangsaeejin-tang extract and Naeso-san extract were administered after gastro-inflammation is elicited. This study examined the anti-inflammation effects and distribution of mucus secreting cells, zonula occludin-1 (ZO-1), heat shock protein (HSP) 70, periodic acid-schiff reaction stain (PAS), peanut agglutinin (PNA), cyclooxygenase-1 (COX-1), 5-bromo-2'-deoxyuridine (BrdU), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-${\kappa}B$) p65, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Results : 1. The hemorrhagic erosion and damaged mucus secreting cell, the positive reaction HSP70 increased in the control group, but decreased in the Eejin-tang, Hyangsaeejin-tang and Naeso-san groups. 2. The positive reaction of ZO-1, PAS, PNA, COX-1 and BrdU decreased in the control group, but increased in the Eejin-tang, Hyangsaeejin-tang and Naeso-san groups. 3. The positive reaction of NF-${\kappa}B$ p65, iNOS and COX-2 increased in the control group, but decreased in the Eejin-tang, Hyangsaeejin-tang and Naeso-san groups. Conclusions : Among the three extracts, the effects were in the order of Naeso-san, Hyangsaeejin-tang and Eejin-tang group, Naeso-san being the most effective.

• Biomolecules & Therapeutics
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• v.24 no.4
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• pp.418-425
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• 2016

We measured anti-nociceptive activity of prim-o-glucosylcimifugin (POG), a molecule from Saposhnikovia divaricate (Turcz) Schischk. Anti-nociceptive or anti-inflammatory effects of POG on a formalin-induced tonic nociceptive response and a complete Freund's adjuvant (CFA) inoculation-induced rat arthritis pain model were studied. Single subcutaneous injections of POG produced potent anti-nociception in both models that was comparable to indomethacin analgesia. Anti-nociceptive activity of POG was dose-dependent, maximally reducing pain 56.6% with an $ED_{50}$ of 1.6 mg. Rats given POG over time did not develop tolerance. POG also time-dependently reduced serum TNF${\alpha}$, IL-$1{\beta}$ and IL-6 in arthritic rats and both POG and indomethacin reduced spinal prostaglandin E2 ($PGE_2$). Like indomethacin which inhibits cyclooxygenase-2 (COX-2) activity, POG dose-dependently decreased spinal COX-2 content in arthritic rats. Additionally, POG, and its metabolite cimifugin, downregulated COX-2 expression in vitro. Thus, POG produced potent anti-nociception by downregulating spinal COX-2 expression.

• Journal of Physiology & Pathology in Korean Medicine
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• v.19 no.6
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• pp.1599-1603
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• 2005

The study was designed to investigate the effects of Leonuri herba extract (LHE) on the change of regional cerebral blood flow (rCBF) and mean arterial blood pressure (MABP) in normal rats, and further to determine the mechanism of action of LHE. The results in normal rats were as follows, LHE significantly increased rCBF in a dose-dependent manner, and MABP did not change in a dose-dependent manner. This results were suggested that LHE significantly increased rCBF by dilating pial arterial diameter. The LHE-induced increase in rCBF was significantly inhibited by Pretreatment with indomethacin(1 mg/kg, i.p.), an inhibitor of cyclooxygenase, and was significantly inhibited by methylene blue($10{\mu}g/kg$, i.p.), an inhibitor of guanylate cyclase. The LHE-induced MABP did not change by pretreatment with indomethacin but was significantly inhibited by methylene blue. This results were suggested that the mechanism of LHE was mediated by cyclooxygenase.

• Journal of Physiology & Pathology in Korean Medicine
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• v.18 no.3
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• pp.783-788
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• 2004

Cheonmabanhwa- Tang (CBT) has been used in the Oriental Medicine for many centuries as a therapeutic agent for dizziness due to Poong-Dam, We reported that CBT had effects on the cerebral hemodynamics [regional cerebral blood flow (rCBF), pial arterial diameter (PAD), and mean arterial blood pressure (MABP)] in normal and cerebral ischemic rats. Therefor we designed to determine the mechanism of action of CBT. The changes of rCBF and MABP were determinated by laser-Doppler flowmetry(LDF), and the change of PAD was determinated by video-microscopy. The results were as follows: The CBT-induced increase in rCBF was significnatly inhibited by pretreatment with indomethacin (IDN, 1 ㎎/㎏, i.p.), an inhibitor of cyclooxygenase, or methylene blue (MTB, 10 ㎍/㎏, i.p.), an inhibitor of guanylate cyclase. The CBT-induced increase in PAD was also significantly inhibited by pretreatment with IDN or MTB. The CBT-induced increase in MABP was also significantly inhibited by pretreatment with IDN or MTB. In conclusion, it is suggested that CBT causes a diverse effect on cerebral hemodynamics via mediation of cyclooxygenase and guanylate cyclase.