• Journal of Chest Surgery
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• 제33권3호
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• pp.221-229
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• 2000

Background: Thromboxane A2 and endothelin-1 are the potent vasoconstrictors affecting pulmonary pathophysiology in response to whole body inflammatin following CPB. Aprotinin, as an antiiflammatory agent, may decrease the release of such vasoactive substance from pulmonary tissues, preventing pulmonary hypertension after cardiopulmonary bypass. Material and Method: Ten mongrel dogs(Bwt. ac. 20kg) were subjected to cardioupulmonary bypass for 2 hours and postbypass pulmonary vascular resistance(0, 1, 2, 3 hours) were compared with prebypass level. The dogs were divided into 2 groups; control group(n-5) and aprotinin group(n=5). In the aprotinin group, aprotinin was administered as follows; 50,000 KIU/kg mixed in pump priming solution, 50,000 KIU/kg prebypass intravenous infusion over 30 minutes, 10,000 KIU/kg/hour postbypass continuous infusion. Prebypass and postbypass 0, 1, 2, 3 hour pulmonary vascular resistance were measured. At prebypass and postbypass 0, 90, 180 minutes, blood samples were obtained from pulmonary arterial and left atrial catherers for the assay of plasma thromboxane B2 a stable metabolite of thromboxane A2, and endothelin-1 concentrations. Result: The ratios of pustbypass over prebypass pulmonary vascular at postbypass 0, 1, 2, 3 hours were 1.28$\pm$0.20, 1.82$\pm$0.23, 1.90$\pm$0.19, 2.14$\pm$0.18 in control group, 1.58$\pm$0.18, 1.73$\pm$0.01, 1.66$\pm$0.10, 1.50$\pm$0.08 in aprotinin group ; the ratios gradually increased in control group while decreased or fluctuated after postbypass 1 hour in aprotinin group. There was statistically significant difference between control group and aprotinin group at postbypass 3 hours(P=0.014). Pulmonary arterial plasma concentration of thromboxane B2(pg/ml) at prebypass, postbypass 0, 90, 180 minutes were 346.4$\pm$61.9, 529.3$\pm$197.6, 578.3$\pm$255.8, 493.3$\pm$171.3 in control group, 323.8$\pm$118.0, 422.6$\pm$75.6, 412.3$\pm$59.9, 394.5$\pm$154.0 in aprotinin group. Left atrial concentrations were 339.3$\pm$89.2, 667.0$\pm$65.7, 731.2$\pm$192.7, 607.5$\pm$165.9 in control group, 330.0$\pm$111.2, 468.4$\pm$190.3, 425.4$\pm$193.6, 4.7.3$\pm$142.8 in aprotinin group. These results showed decrement of pulmonary thromboxane A2 generation in aprotinin group. Pulmonary arterial concentrations of endothelin-1(fmol/ml) at the same time sequence were 7.84$\pm$0.31, 13.2$\pm$0.51, 15.0$\pm$1.22, 16.3$\pm$1.73 in control group, 7.76$\pm$0.12, 15.3$\pm$0.71, 22.6$\pm$6.62, 14.9$\pm$1.11 in aprotinin group. Left atrial concentrations were 7.61$\pm$17.2, 57.1$\pm$28.4, 18.9$\pm$18.2, 31.5$\pm$20.5 in control group, 5.61$\pm$7.61, 37.0$\pm$26.2, 28.6$\pm$21.7, 37.8$\pm$30.6 in aprotinin group. These results showed that aprotinin had no effect on plasma endothelin-1 concentration after cardiopulmonary bypass. Conclusion: Administration of aprotinin during cardiopulmonary bypass could attenuate the increase in pulmonary vascular resistance after bypass. Inhibition of pulmonary thromboxane A2 generation was thought to be one of the mechanism of this effect. Aprotinin had no effect on postbypass endothelin-1 concentration.

• 생약학회지
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• 제51권4호
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• pp.231-237
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• 2020

Euchrestaflavanone B (EFB) is a flavonoid that can be found in root bark, particularly in Cudrania tricuspidata (C. tricuspidata). The extract of C. tricuspidata is widespread throughout Asia and used in traditional medicine. In a previous study, we found anti-platelet effects of substances isolated from C. tricuspidata on collagen-induced human platelets. However, the C. tricuspidata still contains numerous substances, thus, we have searched new candidate, EFB isolated from C. tricuspidata for anti-platelet effect. Our results showed that EFA inhibited collagen-induced platelet aggregation and glycoprotein IIb/IIIa (αIIb/β3)-mediated signaling events, including platelet adhesion, granule secretion, thromboxane A2 production and clot retraction. These results suggest that EFA has inhibitory effects on human platelet activities and thrombus formation and has potential value as a natural substance for preventing platelet-induced thrombosis.

• Biomolecules & Therapeutics
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• 제3권2호
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• pp.132-135
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• 1995

Several clofibrate congeners (bezafibrate, gemfibrozil and fenofibrate) were investigated the relationship between effects on the aggregation induced by aggregating agents (thrombin, arachidonic acid, ADP and collagen) and arachidonic acid metabolism in rabbit homogenized platelet. In platelet aggregation study, all drugs produced no significant inhibition (data not shown) in arachidonic acid and thrombin. Also platelet aggregation by ADP was not changed in bezafibrate and Inhibited dose dependently in fenofibrate and gemfibrozil. Platelet aggregation by collagen was inhibited dose dependently and significantly (from p<0.5 to p<0.001) by gemfibrozil and fenofibrate at concentrations between 20 and 400 $\mu$M. In arachidonic acid metabolism study, synthesis of thromboxane $B_2$ was not changed in rabbit platelet membranes and that of prostaglandin $E_2$ and $F_{2{\alpha}}$ was slightly increased by all drugs. It was concluded that clofibrate congeners inhibited ADP and collagen induced rabbit platelet aggregation and inhibition of collagen induced aggregation was probably mediated through some mechanism (pathway) other than arachidonic acid metabolism, judging from arachidonic acid metabolites (thromboxane $B_2$, prostaglandin $E_2$and $F_{ 2{\alpha}}$) synthesis in rabbit homogenized Platelet.

• Journal of Chest Surgery
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• 제23권2호
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• pp.222-230
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• 1990

Protamine, a polycationic peptide extracted from fish, has been widely used for the reversal of anticoagulant action of heparin. However it may cause untoward circulatory side effects including hypotension and bradyarrhythmia. Nowadays, histamine and prostacyclin are regarded as one of the causative agents in the underlying mechanism of hemodynamic changes. To certify the possible role of histamine and prostacyclin, we observed simultaneous changes of the hemodynamic status, plasma concentration of thromboxane B, and circulating platelet count before and after intravenous injection of protamine. Experimental dogs, weighing 12-14kg, were divided into 2 groups; group A animals [n=10], were pretreated with indomethacin[2.5mg/kg] and group B animals[n=10] were pretreated with chlorpheniramine[0.5mg/kg] Heparin[3mg/kg] and protamine [3mg/kg] were administered sequentially in both groups. The results were as follows ; 1. The mean systemic arterial pressure was maintained well in groups A, whereas in group B it decreased from 165\ulcorner18mmHg to 138\ulcorner30mmHg[p<0.01] and 151\ulcorner21 mmHg[p<0.05] at 1 minute and 2 minutes after protamine injection. The mean pulmonary arterial pressure was not changed significantly in group A, whereas in group B it increased from 852 mmHg to 11\ulcorner3 mmHg[p<0.05], 11\ulcorner3 mmHg[p<0.05] and 10\ulcorner3 mmHg[p<0.05] at 1 minute, 3 minutes and 5 minutes after protamine injection. 2 The thromboxane B2 was not changed significantly in group A, whereas in group B it increased from 399\ulcorner401 \ulcornerg/ml to 744\ulcorner615 \ulcornerg/ml[p<0.05] and 814\ulcorner1070 \ulcornerg/ml [p<0.0 5] at 1 minute and 3 minutes after protamine injection without concomitant changes of pulmonary vascular resistance and pulmonary capillary wedge pressure. 3. The number of circulating platelet was not changed in group A, whereas in group B it decreased from 207100\ulcorner103600/\ulcornerl to 159700\ulcorner90900/\ulcornerl [p<0.05] at 1 minute after protamine injection, Although thromboxane B2 and platelet count were changed significantly after protamine injection, they did not cause the remarkable hemodynamic changes. Considering the above results, hemodynamic changes may be caused mainly by prostacyclin rather than thromboxane or platelet. Therefore, the pretreatment with cyclooxygenase inhibitor would be beneficial to prevent circulatory adverse effects of protamine for the patients undergoing cardiac surgery.

• Journal of Nutrition and Health
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• 제32권4호
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• pp.384-393
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• 1999

The degree of platelet aggregation, thromboxane B2(TXB2)formation and fatty acid composition of platelet phospholipids(PL) were investigated in 24 healthy male subjects who for five weeks consumed either corn oil(CO) rich in linoleic acid(LA), perilla oil (PO) rich in $\alpha$-linoleic acid($\alpha$-LAN), or canola oil(CNO) rich in oleic acid(OA) as a major fat source. Total fat intake was 30% of total calories and prescribed oil intake of each dietary group was 50% of the total fat intake. In the CO group, significantly decreased contents of polyunsaturated fatty acids(PUFA), n-6 PUFA, n-3 PUFA and eicosapentanoic acid(EPA) were observed, and significantly increased contents of OA and saturated fatty acids(SFA) were observed in platelet PL after 3 weeks and 5 weeks of dietary treatment. In the PO group, contents of OA and docosahexanoic acid(DHA) were increased, and the ratio of n-6/n-3 was decreased significantly in platelet PL after dietary treatment. The CNO group showed significatnlty decreased contents of PUFA, P/S ratio, n-6 PUFA, LA,(EPA+DHA)/arachidonic acid(AA), and significantly increased SFA contents after 3 weeks of the oil-based diet. The dietary-induced effects on fatty acid composition of platelet PL were observed mostly after 3 weeks of the oil-based diet. The dietary-induced effects on fatty acid composition of platelet PL were observed mostly after 3 weeks. Plasma TXB2 levels were increased after 3 and 5 weeks of dietary treatment. However, only the CO and CNO groups showed significantly increased plasma TXB2 levles after 3 and 5 weeks of dietary treatment. However, only the CO and CNO groups showed significantly increased plasma TXB2 levels after 5 weeks of experimental diets, when compared with initial values. Degree of platelet aggregation increased only in the CO group after dietary treatment. As a result, at week 5 the degree of platelet aggregation of the CO group was significantly higher than those of the PO and CNO groups. Among the three oil-based diets, the PO-based diet seems to have beneficial effects on atherosclerosis by influencing plasma TXB2 levels and the degree of platelet aggregation, while the CO-based diet showed the most adverse effects. Our results imply that plasma TXB2 levels might be affected by dietary fatty acid composition.

• 대한약리학회지
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• 제20권1호
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• pp.41-46
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• 1984

카드뮴중독으로 혈소판응집이 항진되어 고혈압 또는 동맥경화증이 발생한다는 연구보고를 감안하여 가토와 흰쥐의 생체내 실험으로서 미세혈전의 형성, Malondialdehyde(MDA) 및 thromboxane $B_2(TXB_2)$치에 미치는 카드뮴의 효과를 검토하고, in vitro실험으로 카드뮴을 처치한 가토 대동맥절편이 혈소판응집에 미치는 영향을 관찰하였으며, prostacyclin의 합성능력을 측정하여 그 결과를 다음과 같이 요약하였다. 1)Cadmium chloride 2mg/kg을 매주 동물의 복강내에 주입하였을 때 미세혈전형성이 증가되었다. 2) 카드뮴 중독동물의 platelet-rich plasma (PRP)는 MDA와 $TXB_2$형성이 정상동물에서 보다 현저히 증가되었다. 3) 카드뮴을 중독시킨 가토의 platelet-poor plasma (PPP)에서의 lipid peroxide치는 대조군과 차이가 없었다. 4) In vitro 실험으로, 가토대동맥 절편에서의 6-keto-$PGF_{1{\alpha}}$의 생성은 카드뮴 농도에 비례하여 억제되었고 이때 혈소판 응집률의 증가와 평행하였다. 5) 이상의 결과로서 카드뮴은 동맥내피세포에서 prostacyclin 합성을 억제할 뿐만 아니라 혈소판에서 $TXA_2$합성을 촉진시켜 그 결과로 혈소판 응집률을 증가시켰음을 알 수 있었다.

• 생약학회지
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• 제26권2호
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• pp.139-147
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• 1995

Crinum asiaticum var. japonicum is a wild plant growing only in Jeju-island, Korea, and in Japan. The whole part of this plant has been known to have the pharmacological actions such as analgesic, anti-inflammatory, platelet-aggregation inhibitory, antitussive, and expectorant. With these assumed actions, the leaves (Crinum folium) of this plant has been used in the folk remedies for arthritis and arthralgia. There is, however, no scientific evidences for the pharmacological actions of Crinum asiaticum var. japonicum. In the present study, the analgesic, anti-inflammatory, and platelet-aggregation inhibitory actions of Crinium folium were evaluated using writhing test, tail-flick test, carrageenin antiedema test, in vitro thromboxane $B_2$ quantitation assay and in vitro platelet aggregation test. In order to obtain the partially purified fraction whose pharmacological action is excellent, the methanol extract of Crinium folium was fractionated consecutively into four biological fractions such as ether, ethyl acetate, butanol, and water fractions and their pharmacological actions of the fractions were investigated. Putting our results together, Crinium folium, especially ethyl acetate fraction was proven to have significant analgesic, anti-inflammatory and platelet-aggregation inhibitory actions by inhibition of prostanoids biosynthesis as one of its mechanism of action.

• Journal of Applied Biological Chemistry
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• 제66권
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• pp.114-121
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• 2023

선택적 cyclooxygenase (COX)-2 억제제는 기존의 비스테로이드성 소염제의 위장 부작용을 줄일 수 있는 새로운 대체제이다. 하지만, 최근 혈전을 일으켜 심혈관 질환의 위험을 증가시킨다는 보고가 있다. 따라서 본 연구에서는 유효성분인 ursolic acid를 각각 40, 50%로 극대화한 로즈마리 추출물(RE)의 항염증 효과와 이에 따른 심혈관 부작용의 안전성을 확인하였다. RE의 COX 효소 활성 저해 평가 결과 40, 50% RE는 100 ㎍/mL에서 양성 대조군인 celecoxib 및 rofecoxib와 비슷한 COX-2 저해 활성을 보였고, COX-1 저해 활성은 미미하였다. 이후 Lipopoly-saccharide (LPS)를 조건에 따라 처리한 RAW 264.7 세포에 40, 50% RE 1 ㎍/mL를 처리하여 COX-2, COX-1 유전자 발현, 세포 배양액의 prostaglandin E₂ (PGE₂), thromboxane B₂ (TXB₂) 농도를 확인하였다. 실험 결과 COX-2 유전자 발현은 40% RE가 LPS를 24시간 후처리한 조건에서 감소하였고, 40, 50% RE는 COX-1 유전자 발현 및 PGE₂, TXB₂ 농도에는 유의한 영향을 주지 않는 것으로 확인되었다. 따라서 RE는 혈전 생성에 관여하는 prostaglandins의 균형에 영향을 주지 않아 심혈관 혈전 생성의 위험성이 적을 것으로 사료된다.

• Journal of Nutrition and Health
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• 제28권11호
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• pp.1078-1090
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• 1995

This study was undertaken to elucidate the effect of DHA rich fish oil(DHA rich oil) added to different dietary fats on thrombosis and lipid peroxidation. Rats were fed perilla oil, sesame oil and beef tallow with or without DHA rich oil for 12 weeks. Bleeding time was the longest in Perilla oil groups with or without DHA rich oil. The productions of thromboxane B2(TX B2) and 6-keto Prostaglandin F1$\alpha$(6-keto PG F1$\alpha$) were the highest in Esame oil group without DHA rich oil. Bleeding time tended to be extened and group showed the most antithrombotic effect among three oil groups when DHA rich oil added. The antithrombotic effect by DHA rich oil addition seemed to be resulted from the increase of dietary n-3 fatty acid rather than DHA. And there was not the difference in antithrombotic effect between DHA and $\alpha$-linolinic acid. The level of TBARS(thiobarbituric acid reactive substances) in plasma and liver, and the activities of lipid peroxide metabolizing enzymes(catalase, superoxide dismutase and gluthathion peroxidase) in erythrocyte and liver were not affected by the dietry fat type and DHA rich oil addition, except that activity of hepatic catalase was increased by DHA rich oil addition. Therefore it revealed the DHA level added in this study seldom affected lipid peroxidation. However, it dose not conclude that DHA level of this study make low production of lipid peroxide because the peroid of our study was short.

• 대한약학회:학술대회논문집
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• 대한약학회 2002년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.1
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• pp.130.2-131
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• 2002