• Archives of Reconstructive Microsurgery
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• 제21권1호
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• pp.61-67
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• 2012

Purpose: The purpose of this study was to investigate the role of mast cells and their product, histamine and leukotriene in ischemia-reperfusion injury. Methods: Forty Sprague-Dawley rats were divided into four groups. (Group I: Control group without ischemia, Group II: Normal saline with ischemia, Group III: Cimetidine with ischemia, Group IV: Zafirlukast with ischemia) Skin flap was elevated and ischemic insult was given by clamping the artery for 12 hours. Before reperfusion, the rats were treated with saline, cimetidine and zafirlukast. Flap survival was evaluated at 7 days. Neutrophil counts, mast cell counts were evaluated 24 hours after reperfusion. Results: Flap survival rate in the control group was 92.33%, whereas normal saline group had 37.34% survivals. Cimetidine and zafirlukast treated group showed significantly higher survival rates than normal saline group. The neutrophil and mast cell counts in cimetidine and zafirlukast treated group were significantly decreased than normal saline group. Cimetidine treated group showed higher survival rate and lower cell counts than zafirlukast treated group. Conclusion: The administration of cimetidine and zafirlukast can decrease neutrophils and mast cells caused by ischemia-reperfusion and increase flap survivals. It is suggests that antihistamine and leukotriene receptor antagonist have protective effect against ischemia-reperfusion injury to skin flap in rat.

• The Korean Journal of Physiology and Pharmacology
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• 제1권5호
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• pp.573-580
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• 1997

In this report, the inhibitory action of eupatilin was investgated by using leukotriene $D_4$ in the human neutrophils and Kato III cells (Gastric adenoma cells as a substitute for gastric mucosal cells) stimulated by Helicobacter pylori. Leukotriene $D_4$ ($LTD_4$) was released from both neutrophils and Kato III cells when these cells were incubated with H. pylori. The release of $LTD_4$ increased time-dependently and the maximum release of $LTD_4$ was $2.3{\sim}2.5$ pmol. But in the presence of eupatilin, the release of $LTD_4$ from these cells was inhibited in a dose-dependent manner. In the neutrophils, the release of $LTD_4$ was suppressed to 70% and 50% of the control levels when neutrophils was incubated with 0.01 and 0.1 mM of eupatilin. In the Kato III cells, the release of $LTD_4$ was suppressed to 59% and 27% of the control levels by adding 0.01 and 0.1 mM of eupatilin. We estimated the intracellular $Ca^{2+}$ levels when Kato III cells and neutrophils were stimulated by H. pylori using $^{45}Ca$. But the suppressive effect of eupatilin on $Ca^{2+}$ influx into these cells was not significant. We also obtained the results that H. pylori induced $Ca^{2+}$ influx into these cells by confocal microscopy, however there was no differences in the dose level of eupatilin. These results were confirmed by 1H Nuclear Magnetic Resonance(NMR) spectroscopy. The NMR patterns of eupatilin in the absence of $Ca^{2+}$ was changed compare with when $Ca^{2+}$ was present, but its effect was not strong.

• Toxicological Research
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• 제18권2호
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• pp.205-213
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• 2002

This study was undertaken to develop a subacute murine model for predicting occurrence of systemic anaphylaxis and to evaluate efficacy of various immunological parameters as the monitoring indices for the occurrence of anaphyalxis. The murine anaphyalxis model was developed through intraperitoneally sensitizing 100 $\mu\textrm{g}$ ovalbumin (OVA) in the presence of 1 mg alum and 300 ng cholera toxin twice a week interval followed by challenging 500 $\mu\textrm{g}$. OVA intravenously. Typical anaphylaxis symptoms were demonstrated at the both BALB/c mice, a strain prone to type-2 response, and C57BL/6 mice. a strain prone to type-1 response. Level of plasma histamine was approximately 50-fold or 30-fold higher in the mice sensitized with OVA than the mice sensitized with alum plus cholera toxin or the saline-treated mice after OVA challenge, respectively. Sensitization and challenge with OVA significantly enhanced plasma leukotriene $B_4$ level but not IgE levels in comparison with the control mice, which indicated the role of leukotriene $B_4$ for progression of anaphyalxis. Furthermore, among mice suffered from anaphylaxis, levels of OVA-specific IgGl were significantly higher in the BALB/c mice than in the C57BL/6 mice, which implied the genetic susceptibility for the induction of systemic anaphylaxis. Conclusively, simultaneous evaluation of histamine, leukotriene $B_4$, and allergen-specific IgG isotype may serve as more efficient monitoring tool for vaccine-related anaphyalxis.

• Clinical and Experimental Pediatrics
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• 제59권6호
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• pp.276-279
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• 2016

Sjogren-Larsson syndrome (SLS) is a rare autosomal recessive neurocutaneous disorder with worldwide incidence of 0.4 per 100,000 people. It is characterized by the triad of congenital ichthyosis, spastic diplegia or quadriplegia, and mental retardation. Herein we report a 2-year-old male child with SLS, asthma, and recurrent pneumonia. SLS was confirmed by a molecular genetics study that revealed a deletion mutation in the ALDH3A2 gene. An ALDH3A2 gene mutation results in dysfunction of the microsomal enzyme fatty aldehyde dehydrogenase and impaired metabolism and accumulation of leukotriene B4, which is a key molecule and a pro-inflammatory mediator in developing allergic diseases, especially asthma. An increased level of leukotriene B4 has been reported in SLS patients. As far as we are aware, this is the first report of SLS associated with asthma and recurrent pneumonia. In conclusion, pediatricians should be aware of and evaluate patients with SLS for possible associated asthma and allergic disorders.

• 약학회지
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• 제33권6호
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• pp.319-323
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• 1989

Polymorphonuclear leukocyte (PMNL) was obtained from peritoneal cavity in rat treated with casein. Effects of divalent cations and drugs on leukotriene $B_4(LTB_4)$ formation from arachidonic acid in the PMNL were determined by HPLC assay. 5-Lipoxygenase, a key enzyme for $LTB_4$ formation from arachidonic acid, exhibited $V_{max}$ at $1\;{\times}\;10^{-5}M$, and $K_m$ at $9.89\;{\times}\;10^{-5}M$ of arachidonic acid. Optimal $Ca^{++}$ concentration for the enzyme activity was $1\;{\times}\;10^{-5}M$ but $Zn^{++}$ did not show any significant effects on the $LTB_4$ formation. Indomethacin and caffeic acid exhibited inhibitory effects on the $LTB_4$ formation at $1\;{\times}\;10^{-5}M$ and $4\;{\times}\;10^{-5}M$, respectively. However, 6-aminohexanoic acid did not show any significant effects on the $LTB_4$ formation.

• Archives of Pharmacal Research
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• 제22권6호
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• pp.549-553
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• 1999

The antipruritic effect of DA-5018m a capsaicin derivative, was examined in mice. Male ICR mice were topically pretreated with Zostrix-HP (0.075% capsaicin cream), 0.1%, 0.3% DA-5018 cream or cream base (control) twice daily for 4 days. One hour after the last application, itch was induced either by compound 48/80 ($50{\mu}g$, s.c.) or leukotriene B4 (0.03 nmol, i.d.) injection into the rostral back of the animals, and the number of scratches made by the animals at the injection site was counted for 60 min post-injection. DA-5018 cream (both 0.1 and 0.3%) significantly inhibited compound 48/80-induced scratching when compared with the cream base control (p<0.01), which Zostrix-HP showed minimal inhibition of the scratching behavior. In leukotriene B4-induced itch model, Zostrix-HP and 0.3% DA-5018 cram significantly inhibited the scratching during the first 10-min period (p<0.01). The results suggest that DA-5018 cream can be used as an antipruritic agent and warrant clinical evaluation.

• BMB Reports
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• 제41권2호
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• pp.139-145
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• 2008

We cloned and pharmacologically characterized the guinea pig cysteinyl leukotriene (CysLT) 2 receptor (gpCysLT2). gpCysLT2 consists of 317 amino acids with 75.3%, 75.2%, 73.3% identity to those of humans, mice and rats, respectively. The gpCysLT2 gene is highly expressed in the lung, moderately in eosinophils, skin, spleen, stomach, colon, and modestly in the small intestine. CysLTs accelerated the proliferation of gpCysLT2-expressing HEK293. Leukotriene C4 (LTC4) and Leukotriene D4 (LTD4) enhanced the cell proliferation higher than Bay-u9773, a CysLT2 selective partial agonist and a nonselective antagonist for CysLT receptors. Bay-u9773 did not antagonize the cell proliferation by LTC4 and LTD4. Despite the equipotency of the mitogenic effect among these chemicals, calcium mobilization (CM) levels were variable (LTC4 > LTD4 >> Bay-u9773), and Bay-u9773 antagonized the CM by LTC4. Moreover, the Gi/o inhibitor pertussis toxin perfectly inhibited agonist-induced cell proliferation. These results reveal that cell proliferation via CysLT2 signaling was mediated by Gi/o signaling but independent of calcium mobilization.

• 한국약용작물학회지
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• 제24권5호
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• pp.401-407
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• 2016

Background: Salvia has been widely cultivated for use in flavoring and folk medicines in many countries, including Korea and China. In this study, we investigated the anti-inflammatory activity and the underlying active compounds of Salvia extract and its fractions. Methods and Results: The anti-inflammatory activity was measured by assessing the inhibition of cysteinyl leukotriene production in rat basophilic leukemia (RBL)-2H3 mast cells. Salvia plebeia R. Br. was found to have the most potent inhibitory activity on leukotriene production than S. japonica and S. chanroenica had. Fifty percent ethanol extracts of S. plebeia R. Br. were successively partitioned with n-hexane, methylene chloride, ethyl acetate, 1-butanol and water. The ethyl acetate (EtOAc) fraction showed stronger anti-inflammatory activity than other solvent fractions did. The EtOAc fraction was subjected to silica gel column chromatography elution with a chloroform and methanol gradient system (100 : 1 ${\rightarrow}$ 1 : 1) yielding 10 fractions. Three kinds of fractions (chloroform:methanol = 20 : 1, 10 : 1 and 5 : 1) showed high inhibitory activity on leukotriene production. We confirmed the major compounds with anti-inflammatory activity from S. plebeia R. Br. Conclusions: In this study, the major components of S. plebeia that showed leukotriene production inhibitory activity were isolated using solvent extraction and silica gel column chromatography. Rosmarinic acid, hispidulin and luteolin were identified as the major compounds with anti-inflammatory effect.

• 한국영양학회:학술대회논문집
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• 한국영양학회 2002년도 춘계학술대회
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• pp.93-93
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• 2002

• Journal of Applied Biological Chemistry
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• 제44권4호
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• pp.199-201
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• 2001

A phenolic substance was isolated from the bark of Pinus koraiensis. It was identified to be pinostilbenoside. Its anti-$LTD_4$ activity was evaluated using isolated guinea pig trachea, and its half maximal bronchodilating activity ($EC_{50}$) was $593{\pm}56{\mu}g{\cdot}ml^{-1}$. Because it is not known that stilbene derivatives possess anti-asthmatic activity through $LTD_4$ antagonism, here we report the result.