• Title/Summary/Keyword: rat platelets

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Effects of Various Quinones (Menadione, Benzoquinone and 2,3-Dimethoxy-1,4-naphthoquinone) on Rat Platelets (Quinones (menadione, benzoquinone, 및 2,3-dimethoxy-1,4-naphthoquinone)의 혈소판 세포독성)

  • 승상애;이무열;이주영;김미정;정진호
    • Toxicological Research
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    • v.12 no.2
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    • pp.289-293
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    • 1996
  • Our previous studies demonstrated that quinone (menadione) is cytotoxic to rat platelets. In an attempt to assess the relative contributions of redox cycling and/or arylation in quinone-induced cytotoxicity, we have studied three quinones with different mechanisms: 2, 3-dimethoxy-1, 4-naphthoquinone (DMNQ; pure redox cycler), menadione (both redox cycler and arylator), and 1, 4-benzoquinone (pure arylator). The order of redox cycling capacity in platelet rich plasma (PRP) isolated from rats was menadione>DMNQ>1, 4-benzoquonone, which was consistent with the previous studies using isolated hepatocytes. 1, 4-Benzoquinone was more toxic to rat platelets than menadione, while DMNQ did not cause cell death at all. Lactate dehydrogenase inhibition studies revealed that 1, 4-benzoquinone inhibited significantly in a time-dependent manner, while menadione and DMNQ did not at all. These results suggested that arylation by quinone compounds might play a critical role in quinone-induced cytotoxicity in rat platelets.

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Evaluation of Cytotoxicity to Rat Platelets by Menadione-Glutathione Conjugate and its Stability in Biological Assay System (Menadione의 대사체인 Menadione-Glutathione Conjugate(MEN-SG)가 흰쥐 혈소판에 미치는 세포독성의 평가 및 MEN-SG의 안정성에 관한 연구)

  • Seo, Dong-Chul;Chung, Sun-Hwa;Lee, Joo-Young;Kim, Mee-Jeong;Chung, Jin-Ho
    • Toxicological Research
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    • v.11 no.2
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    • pp.295-302
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    • 1995
  • Menadione-ghitathione conjugate (MEN-SG), a metabolite of menadione, is known to be a redoxcycler in rat hepatocyte subcellular fraction. Therefore, it was assumed that MEN-SG could exert cytotoxlclty to ral platelets, another target tissue of menadione. We first synthesized MEN-SG, the identity of which was verified by mass, $^1{H}$-NMR and UV-visible spectra. In addition, the stability of MEN-SG was investigated in biological assay system. MEN-SG was degraded in a time-dependent manner in DMSO which had been used as a vehicle and thus, tris-HCl buffer was used as a vehicle of MEN-SG despite the low solubility in it. Perchloric acid as well as platelets itself did not affect the stability of MEN-SG. Our next attempt was the evaluation of cytotoxicity of MEN-SG in rat platelets. MEN-SG did not induce cytotoxicity to rat platelets measured by two different methods, LDH release and turbidity changes. The extents of oxygen consumption by MEN-SG in intact platelets were significantly lower than those by menadione, though it had been observed that oxygen consumptions by menadione and MENSG were similar in subcellular fractioas of platelets. These results suggest that MEN-SG is not toxic to rat platelets despite its redox cycling capacity and glutathione conjugation reaction of menadione could be regarded as a detoxification process.

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The Role of Nitric Oxide in Menadione-Induced Cytotoxicity in Rat Platelets (Menadione에 의한 흰쥐 혈소판 세포독성에서 nitric oxide의 역할)

  • 승상애;김대병;윤여표;정진호
    • Toxicological Research
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    • v.11 no.2
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    • pp.303-308
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    • 1995
  • Nitric oxide, a physiological transmitter, is reported to mediate cellular injury in various tissues. Its reactivity to free radical is believed to be one of the reasons for its involvement in cytotoxicity. Menadione, a representative quinone, is cytotoxic to several cell systems including isolated hepatocyte, endothelial cell and red blood cells. Its toxic mechanism is related to oxidative stress, mediated by toxic free radicals. Our previous studies demonstrated that menadione induced cell lysis and increase of oxygen consumption in platelets. It has been reported that platelets have nitric oxide producing enzyme, nitric oxide synthase. Thus, we have investigated to manifest the role of nitric oxide.in menadione-induced cytotoxicity in rat platelets. Menadione induced cytotoxicity in platelets was unaffected by $N^G$-nitro-arginine methyl ester (L-NAME), selective and competitive inhibitor of nitric oxide synthase. We also invesitgated the role of extracellular nitric oxide in menadione-induced cytotoxicity of platelets by addition with sodium nitroprusside (SNP). SNP did not affect platelet cytotoxicity by menadione. These results suggested that nitric oxide which was generated endogeneously or exogeneously might have a negligible role in menadione-induced cytotoxicity in rat platelets.

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Effect of Lipophilic Fraction and Protein Fraction of Korean Red Ginseng on the Production of cGMP In Rat Platelets (Rat 혈소판의 cGMP생성에 있어서 홍삼 지용성 분획과 단백질 분획의 영향)

  • Lee, Man-Hee;Lee, Jung-Hee;Park, Hwa-Jin
    • Journal of Ginseng Research
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    • v.18 no.2
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    • pp.108-112
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    • 1994
  • Rats (Sprague Dawley, male, 200 g) were fed with 15% corn oil containing a large quantity of 18 2 (linoleic acid) for 3 weeks, and were followed by feeding the petroleum ether extracts from Korean red ginseng for 3 weeks. cGMP was produced more in platelets prepared from both 15% corn oil and petroleum ether extracts-fed group than in platelets only 15% corn oil-fed group, indicating that the production of cGMP is increased by feeding the petroleum ether extracts. When this platelet was stimulated by phorbol-12-myristate-13-acetate (PMA), the level of cGMP was decreased. However, the platelets in medium containing protein fraction (200 $\mu\textrm{g}$/ml) was stimulated by PMA, the production of cGMP inhibited by PMA was increased by 3 times or more. These results suggest that both the protein fraction and the petroleum ether extracts from Korean red ginseng are synergistic in the productiorl of cGMP, and they may have the antiplatelet effects.

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Effects of diterpene acids on malondialdehyde generation during thrombin induced aggregation of rat platelets

  • Kosela, Soleh;Rasad, Asri;Achmad, Sjamsul-Arifin;Wachyudi-Wicaksonon;Baik, Soung-Kyung;Han, Yong-Nam;Han, Byung-Hoon
    • Archives of Pharmacal Research
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    • v.9 no.3
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    • pp.189-191
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    • 1986
  • The effects of diterpene acids (i. e. pimaradienoic acid, kaurenoic acid, hydroxy cembratrienoic acid and dihydroxycembratetraenoic acid) on malondialdehyde generation by rat platelets in response to thrombin were studied. All the compounds inhibited the generation of MDA.

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Important Role of Glutathione in Protecting Against Menadione-Induced Cytotoxicity in Rat Platelets

  • Cho, Youn-Sook;Seung, Sang-Ae;Kim, Mee-Jeong;Lee, Joo-Young;Chung, Jin-Ho-Chung
    • Archives of Pharmacal Research
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    • v.19 no.1
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    • pp.12-17
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    • 1996
  • Our previous studies demonstrate that menadione (MEN) is cytotoxic to platelets of rats by depleting glutathione (GSH). In order to clarify whether GSH has a role in protecting against menadione-induced cytotoxicity, the effect of GSH depletors as well as GSH precusors on menadione-induced cytotoxicity was investigated. Cysteine and dithiothreitol (DTT) prevent MEN-induced cytotoxicity in a dose-dependent manner, as determined by LDH leakage and change in turbidity. When platelets were treated with 1-chloro-2,4-dinitrobenzene (CDNB) and diethylmaleate (DEM), both of which deplete intracellular GSH, MEN-induced cytotoxicity was potentiated in the CDNB-treated paltelets, but not in the DEM-treated platelets. These data suggest that the GSH in platelets plays an important role in protecting against cytotoxicity induced by menadione.

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LIPOPHILIC FRACTION FROM KOREAN RED GINSENG REGULATES THE PHOSPHORYLATION OF PLATELET PROTEIN(50KD) BY ELEVATING CYCLIC-GMP IN VIVO AND IN VITRO

  • Park H.J.;Rhee M.H.;Park K.M.;Nam K.Y.;Lee J.H.;Park K.H.
    • Proceedings of the Ginseng society Conference
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    • 1993.09a
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    • pp.94-101
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    • 1993
  • Lipophilic fraction(LF) from Panax ginseng C.A. Meyer inhibited the aggregation of human platelets induced by th rombin(0.1u/$m{\ell}$). LF and Molsidomine(vasodilator) induced the stimulation of cGMP - elevation and 50KD - Phosphorylation. and then the inhibition of 20KD - Phosphorylation in human platelets activated by thrombin. LF also inhibited the $Ca^{2-}-influx$ into platelets. When rat(SD : male) was fed with LF, the level of cGMP was increased in rat platelets stimulated by collagen and thrombin. On the other hand. verapamil, $Ca^{2-}-antagonist$ increased cAMP level ;n platelet stimulated by thrombin. but LF does not affected. However LF potently inhibited the thromboxane $A_2(TXA_2)$ production. The results suggest that the inhibitory effects of LF are mediated by regulation the phosphorylatior. of 50KD via cGMP-elevation and depend upon the decrease of $TXA_2$ level.

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Improvement of Haemostasis Mediated by Anti-Platelet Activities by Plant Vinegar (목초액의 혈소판 응집억제를 통한 혈행개선 작용에 관한 연구)

  • 김영대;배옥남;정승민;정진호
    • Toxicological Research
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    • v.20 no.2
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    • pp.137-142
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    • 2004
  • We investigated the effects of plant vinegar on platelets and blood coagulation system. Plant vinegar inhibited in vitro platelet aggregation in a concentration dependent manner, when platelets were activated by thrombin and collagen. In addition, plant vinegar showed inhibitory effects on the serotonin secretion induced by thrombin in a concentration dependent manner. However, treatment with plant vinegar to platelets did not induce any cytotoxicity, as determined by the release of lactate dehydrogenase. Plant vinegar did not change the coagulation parameters such as activated partial thromboplastin time (aPTT) and prothrombin time (PT) using rat citrated plasma. In vivo study revealed that, treatment with plant vinegar prolonged the bleeding time from mouse tail. All these results suggest that plant vinegar might improve blood hemostasis mediated via anti platelet activities.

20(S)-ginsenoside Rg3 inhibits glycoprotein IIb/IIIa activation in human platelets

  • Kwon, Hyuk-Woo
    • Journal of Applied Biological Chemistry
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    • v.61 no.3
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    • pp.257-265
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    • 2018
  • The Panax ginseng Mayer is used in conventional medicine in Asia owing to its preventing effects on thrombosis, hypertension, atherosclerosis, vasorelaxation and myocardial infarction. Because platelets are crucial mediators of cardiovascular diseases, many studies have investigated its functions. The previous study showed the antiplatelet effects of crude ginseng fraction and two of its components, ginsenoside Rg3 (20S and 20R). In addition, ginsenoside Rg3-enriched fraction shows an inhibitory effect on collagen-activated rat platelets. However, the mechanism underlying this effect remains unclear. Thus, I investigated the inhibitory action of ginsenoside Rg3 (20S, G-Rg3) on the regulation of signaling molecules involved in ${\alpha}IIb/{\beta}_3$ activation. I found that G-Rg3, in a cyclic AMP dependent manner, inhibited thrombin-induced activation of human platelets and affinity of fibrinogen and fibronectin with ${\alpha}IIb/{\beta}_3$. Thus, in the present study, G-Rg3 showed an inhibitory effect on glycoprotein IIb/IIIa (${\alpha}IIb/{\beta}_3$) activation, suggesting its potential use for preventing platelet-mediated thrombotic disease.

Pharmacological Mechanism of Action of GS283 and GS386 on Human Platelet and Pig Coronary Artery (관상동맥이완과 혈소판응집에 대한 GS283과 GS386의 약리작용기전에 관한 연구)

  • CHANG, Ki Churl;LEE, Hoi Young;LEE, Goun Woo;KOO, Eui Bon;KANG, Young Jin;LEE, Young Soo
    • Biomolecules & Therapeutics
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    • v.5 no.3
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    • pp.239-245
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    • 1997
  • Trimetoquinol (TMQ) and its analogs are known to have thromboxane $A_2$ antagonistic action. We also reported that GS389, chemically similar to TMQ, has competitive antagonistic action in rat aorta and human platelets. In the present study, we investigated the pharmacological characteristics of GS283 and GS 386, analogs of GS389, using vascular smooth muscle, human platelets and rat brain homogenates. In isolated pig coronary artery (PCA), both of GS283 and GS386 relaxed U46619-contracted rings in concentration dependent manner. Pretreatment with several concentrations of GS283 and GS386 shifted the dose-response curves to the right, and reduced of maximum contration dose-dependently. Furthermore, GS283 and GS386 strongly inhibited $Ca^{2+}$ -induced contraction in the PCA. In human platelets, U46619- and A23187-induced platelet aggregation was inhibited by GS283 and GS386, concentration-dependently. Anti-platelet aggregation was related to the compound\`s ability to inhibit ATP release at each stimulation. In rat brain homogenates, receptor-binding assay resulted that both GS283 and GS386 have a relative affinity to $\alpha$-adrenergic receptor. Taken together. we concluded that the mechamism of action of GS283 and GS86 is not related with in TXA$_2$ receptor but concerned with calcium antagonistic action and a-blocking action.n.

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