Effects of carbocromene on performance and oxidation of FFA and glucose in isolated atria.
Explore the source record for details and available documents.
Animals↗
SEARCH · Search PubMed
Results for “Chromonar”
Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.
Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.
Cloricromene in endotoxemia: role of NF-kappaB.
In this study we investigated, for the first time in vivo, the effect of cloricromene, a cumarine derivative, on NF-kappaB activation in endotoxin-treated rats. Endotoxemia was induced in male rats by the intravenous injection of Salmonella typhosa lipopolysaccharide (LPS; 2 mg/kg/i.v.). In vivo treatment with cloricromene (2 mg/kg/i.v.) 30 min before lipopolysaccharide administration reversed the LPS-induced loss in tone of the aortic rings, improved their reactivity to phenylephrine, decreased both nitric oxide (NO) and TNF-alpha serum levels by inhibiting LPS-induced inducible NO synthase and TNF-alpha mRNA expression, and interestingly inhibited LPS-induced NF-kappaB activation. Our data suggest that cloricromene protects rats from LPS by blocking LPS-induced NF-kappaB activation, leading to inhibition of NO and TNF-alpha overproduction and thereby reversing the LPS-induced vascular hyporeactivity.
Animals↗
Cloricromene, a coumarine derivative, reduced the development of periodontitis in rats.
Recent studies have demonstrated that cloricromene, a coumarin derivative, exerts protective effects in models of inflammation and shock. Tumour necrosis factor plays a pivotal role in the induction of genes involved in physiological processes, as well as in the response to inflammation. We investigated the effect of cloricromene in a rat model of periodontitis. Periodontitis was induced in rats by placing a 2/0 braided silk ligature around the lower left first molar. At day 8 the gingivomucosal tissue encircling the mandibular first molar was removed for evaluation of tumour necrosis factor production, neutrophil infiltration, tissue permeability, nitrotyrosine formation, poly (ADP-ribose) polymerase activation, radiography and histology. Ligation significantly induced an increased tumour necrosis factor production, neutrophil infiltration and a positive staining for nitrotyrosine formation and poly (ADP-ribose) polymerase activation. Ligation significantly increased Evans blue extravasation in gingivomucosal tissue and alveolar bone erosion as evaluated by radiography analysis. Intraperitonal injection of cloricromene (10 mg/kg daily for 8 days) significantly decreased all of the parameters of inflammation as described above. This suggests that cloricromene treatment, which reduced tumour necrosis factor production, may be of benefit in the treatment of periodontitis.
Animals↗
Coronary steal in four models of single or multiple vessel obstruction in dogs.
Explore the source record for details and available documents.
Animals↗
Cloricromene inhibits leukotriene formation by human polymorphonuclear leucocytes by suppressing arachidonate release from membrane phospholipids.
Cloricromene, an antithrombotic agent known to inhibit the release of arachidonic acid (AA) in stimulated human platelets, was tested for its effects on arachidonate release and metabolism in human polymorphonuclear leucocytes (PMNs). Cloricromene dose-dependently suppressed the release of leukotriene B4 (LTB4), as assessed by radioimmunoassay, from both isolated PMNs and human whole blood stimulated with the calcium ionophore A23187 or with serum-treated zymosan (STZ). The inhibitory effect was higher when the concentration of the stimulating agent was weaker. Cloricromene also inhibited dose-dependently the liberation of LTB4, LTC4, LTD4 and 5-hydroxy-6,8,11,14-eicosatraenoic acid as assessed by HPLC in the supernantant of A23187-stimulated PMNs. Finally, the drug was able to suppress the release of [3H]AA from purified human PMNs prelabeled with the radioactive fatty acid and stimulated with either A23187 or with STZ. The A23187-induced decrease in the radioactivity of phosphatidylinositol, the phospholipid class mainly involved in AA release in stimulated PMNs, was also inhibited by cloricromene. Cloricromene suppresses leukotriene formation in human PMNs by reducing AA release from membrane phospholipids, possibly through interference with phospholipase A2 activation; this activity may contribute to the leucocyte-inhibitory effects reported previously for cloricromene.
Arachidonic Acid↗
The effect of AD6 (8-monochloro-3-beta-diethylamino-ethyl-4-methyl-7-ethoxy- carbonylmethoxycoumarin) on washed human platelet aggregation induced by platelet activating factor (PAF) and epinephrine.
The effect of AD6 (8-monochloro-3-beta-diethylamino-ethyl-4-methyl-7- ethoxycarbonylmethoxycoumarin) was studied in vitro on washed human platelet aggregation and beta-thromboglobulin (beta TG) release induced by PAF alone or in combination with epinephrine. AD6 caused concentration-dependent inhibition of aggregation and beta TG release. Acetylsalicylic acid and the ADP scavenger apyrase were ineffective on the same parameters, while the specific PAF antagonist CV 3988, the Ca2+ antagonist diltiazem and the cyclo-oxygenase-lipoxygenase inhibitors nordihydroguaiaretic acid and BW 755C inhibited aggregation. The results indicate that AD6 is an inhibitor of platelet aggregation in vitro with a mode of action different from cyclo-oxygenase blockade.
4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyraz↗
Cloricromene inhibits the activation of human platelets by ADP alone or in combination with adrenaline.
Cloricromene may inhibit platelet activation induced by several agonists. In this study we report that ADP and adrenaline synergistically promote platelet aggregation and cytoplasmic Ca2+ movements in aequorin-loaded platelets. Cloricromene caused dose-dependent reduction in platelet aggregation and cytoplasmic Ca2+ movements after exposure of the cells to a low concentration of ADP (2 microM) or to a combination of ADP (2 microM) and adrenaline (10 microM). Cloricromene's inhibitory action may be of considerable pharmacological interest since platelet activation by a combination of agonists may mimic the conditions under which thrombosis occurs in vivo.
Adenosine Diphosphate↗
Polymorphonuclear leukocyte-dependent modulation of platelet function: effect of cloricromene.
Cloricromene inhibits the activation of platelets and polymorphonuclear leukocytes (PMN) induced by specific stimuli. We report here that cloricromene caused a concentration-dependent reduction of platelet aggregation, beta-thromboglobulin (beta-TG) release and cytoplasmic Ca2+ movements induced by PMN stimulated with N-formyl-L-methionyl-L-leucyl-L-phenylalanine (fMLP), and enhanced the inhibitory action of unstimulated PMN on platelet responses to the stable endoperoxide analog U46619. These effects may be of pharmacological interest in view of the multiple interactions between platelets and leukocytes that occur in thrombotic and inflammatory diseases.
15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
Cloricromene, a coumarine derivative, protects against lethal endotoxin shock in rats.
Endotoxin shock was induced in male rats by an intravenous (i.v.) injection of Salmonella enteriditis lipopolysaccharide (LPS; 20 mg/kg i.v.). Survival rate, macrophage and serum tumor necrosis factor (TNF-alpha), mean arterial blood pressure (MAP) and white blood cell count were then evaluated. Furthermore the in vitro effect of cloricromene on peritoneal macrophage phagocytosis and TNF-alpha release by primed peritoneal macrophages was investigated. LPS administration caused animal death (0% survival 24 h after endotoxin challenge), hypotension, marked leukopenia and increased the levels of TNF-alpha in both serum and macrophage supernatants. Cloricromene administration (0.5, 1 and 2 mg/kg i.v. 15 min after endotoxin) protected against LPS-induced lethality (100% survival rate 24 h after endotoxin challenge), reverted LPS-induced hypotension and leukopenia, and decreased TNF-alpha in both serum and macrophage supernatants. Finally, cloricromene, added in vitro to peritoneal macrophages collected from endotoxin-treated rats increased macrophage phagocytosis and reduced TNF-alpha formation by activated mononuclear phagocytes. Our data suggest that cloricromene increases survival rate in endotoxin shock through an inhibition of TNF-alpha production.
Animals↗
Cloricromene synergizes with antiplatelet drugs and nitric oxide-like factor derived from rat peritoneal polymorphonuclear cells.
We report that cloricromene (5-30 microM) inhibited thrombin-induced platelet aggregation and synergized with other antiplatelet compounds. The antiaggregatory effect of subthreshold concentrations of the prostaglandin (PG)I2 analogue, iloprost (0.2 nM), or of sodium nitroprusside (1 micron), acting through a nitric oxide (NO)-like mechanism, was significantly potentiated by co-incubation with cloricromene (5 microM). In addition, cloricromene enhanced the antiplatelet activity of the NO-like factor released by peritoneal rat polymorphonuclear cells. Thus, the present results show that cloricromene possesses direct antiplatelet properties and synergizes with other endogenous as well as exogenous antiplatelet compounds.
Animals↗
Cloricromene inhibits the induction of nitric oxide synthase.
The effect of cloricromene, a coumarin derivative, was investigated on the lipopolysaccharide-stimulated nitric oxide (NO) synthase induction in intact aortas from endotoxin shocked rats and in the murine macrophage cell line J774. Rings of thoracic aortas from lipopolysaccharide (4 mg/kg, i.v.)-shocked rats, contracted with phenylephrine, showed a progressive decrease in tone, that was of a greater magnitude than that of aortas from naive rats. Moreover, a decreased response to the constrictor effect of phenylephrine was observed in aortas from shocked rats. In vivo treatment with cloricromene (2 mg/kg, i.v.) 30 min before lipopolysaccharide administration partially prevented the loss in tone of aortic rings and improved their reactivity to phenylephrine. Murine J774 macrophages activated with lipopolysaccharide (100 ng/ml) produced significant amounts of nitrites (NO2-; 28.2 +/- 3.5 nmol/10(6) cells per 24 h). Cloricromene (2, 20 or 200 microM) added to the cells concomitantly with lipopolysaccharide inhibited NO2- production in a concentration-dependent manner. Maximum inhibition (84.0 +/- 8.0%) was observed when cloricromene (200 microM) was added to the cells 6 h before lipopolysaccharide, whereas it was ineffective when given 6 h after endotoxin. These results demonstrate that cloricromene inhibits the expression but not the activity of the inducible NO synthase.
Amino Acid Oxidoreductases↗
Antioxidants differentially affect nuclear factor kappa B-mediated nitric oxide synthase expression in vascular smooth muscle cells.
Increased 'oxidative stress' resulting in the activation of nuclear factor kappa B (NF-kappa B) is thought to play a crucial role in the cytokine-mediated expression of the inducible isoform of nitric oxide synthase (iNOS) in different cell types. Therefore, the effects of four different antioxidants, carbocromen, chrysin, 3,4-dichloroisocoumarin (DCI) and N-acetylserotonin (NAS), on iNOS expression were investigated in vascular smooth muscle cells (VSMC). All antioxidants strongly reduced the phorbol ester-stimulating superoxide anion formation in native VSMC. Carbocromen (200 microM) and chrysin (50 microM) had no effect, while NAS (1 mM) abolished the increase in nitrine production and iNOS protein abundance in cultured VSMC exposed to interleukin-1 beta (IL-1 beta, 60 U/ml) or the adenyl cyclase activator forskolin (10 microM). DCI also revealed a marked inhibitory effect in IL-1 beta-stimulated VSMC, but was less effective in cells treated with forskolin. DCI, but not NAS, also suppressed the activation of NF-kappa B in VSMC exposed to IL-1 beta, while no significant NF-kappa B activation was detected in forskolin-treated cells. These findings demonstrate that antioxidants differentially affect iNOS expression in VSMC both at the transcriptional level by preventing the activation of NF-kappa B and at the post-transcriptional level, presumably by promoting iNOS mRNA or protein degradation. They also suggest that reactive oxygen intermediates do not play a role in the activation of NF-kappa B by IL-1 beta in VSMC, and that transcription factors other than NF-kappa B mediate the induction of iNOS expression by elevating the intracellular concentration of cyclic AMP.
Animals↗
Ultrastructural modifications of the platelet plasma membrane in vascular diseases and the effect of a carbochromen derivative as studied by freeze-fracture and computer measurement.
A high surface density of the openings of the surface connected canalicular system (SCCS) has been observed in the freeze-fractured plasma membrane of circulating platelets in rabbits fed an atherogenic diet and in hypercholesterolemic type IIa patients. In vitro tests have revealed a correlation between the increased surface density of the SCCS openings and the initial steps of platelet activation. 8-Chlorocarbochromen, a new drug which enhances the in vivo release of prostacyclin from the arterial wall, has been found to be effective in reducing the high surface density of SCCS openings in platelets of rabbits on an atherogenic diet. The present study shows that circulating platelets from patients with peripheral vascular disease present a high surface density of SCCS openings compared to that observed in control subjects. After a single oral administration of 8-chlorocarbochromen, a reduction of the high number of these openings has been observed. Likewise, beta-thromboglobulin levels were found to be high in the patients and to be significantly reduced after oral administration of the drug. This study shows ultrastructural modifications of platelets in conditions related to atherosclerosis and includes data on the effectiveness of 8-chlorocarbochromen in reducing the platelet activation of these patients.
Administration, Oral↗
Cloricromene antagonizes antidipsogenic effects induced by endotoxin, but not by TNF alpha, in the rat.
Intravenous (640 micrograms/kg) or intracerebroventricular (0.5 and 1 microgram) injection of Escherichia coli endotoxin (LPS) causes inhibition of water intake induced by 24 hour period of water deprivation in the rat. Tumor necrosis factor alpha (TNF-alpha; 20 and 40 ng/rat) given into the lateral cerebral ventricle (i.c.v.) causes effects similar to those observed after LPS. Cloricromene, given either intravenously (1 and 2 mg/kg) or i.c.v. (250 and 500 ng), abolished the antidipsogenic effect induced by LPS (administered both i.v. and i.c.v.). Cloricromene (2 mg/kg, i.v. or 500 ng/rat, i.c.v.), on the contrary, did not modify the antidipsogenic effects induced by TNF-alpha. These data indicate that peripherally injected cloricromene (as well as that i.c.v. injected) antagonizes the effects of mediators of LPS on sites regulating thirst and suggest that cloricromene's action may be due to inhibition of brain TNF-alpha formation induced by LPS.
Animals↗
The effect of cloricromene, a coumarine derivative, on leukocyte accumulation, myocardial necrosis and TNF-alpha production in myocardial ischaemia-reperfusion injury.
The effects of cloricromene, a coumarine derivative, were studied in an anaesthetized rat model of coronary artery ligation (60 min) followed by reperfusion (60 min; MI/R). Sham operated rats were used as controls (Sham MI/R). Myocardial ischaemia-reperfusion injury produced a marked myocardial injury (necrotic area/area-at-risk = 68 +/- 4%; necrotic area/total area = 48 +/- 3%) high serum creatinphosphokinase activity (Sham MI/R = 29 +/- 8 U/ml; MI/R = 205 +/- 11 U/ml) and elevated myocardial myeloperoxidase activity (investigated as an index of leukocyte adhesion and accumulation), in the area-at-risk (6.3 +/- 0.2 U x 10(-3)/g tissue) and in necrotic area (6.5 +/- 0.5 U x 10(-3)/g tissue). Furthermore, serum TNF-alpha was undetectable during the occlusion period, but upon the release of the coronary artery significantly increased. At the end of reperfusion, macrophage TNF-alpha was also enhanced. The administration of cloricromene (2 mg/kg, 5 minutes after the onset of reperfusion) significantly reduced myocardial injury (necrotic area/area-at-risk 30 +/- 1.3%; necrotic area/total area = 25 +/- 1.5) blunted the increase in serum creatinphosphokinase activity (92 +/- 5 U/ml) and lowered myeloperoxidase activity in area-at-risk (2.5 +/- 0.2 U x 10(-3)/g tissue) and in necrotic area (2.2 +/- 0.3 U x 10(-3)/g tissue) and decreased the serum and macrophage levels of TNF-alpha. These data indicate that cloricromene exerts beneficial effects on myocardial ischaemia/reperfusion injury. Finally, since we measured increased serum levels of TNF-alpha that were blunted by the cloricromene treatment, our data are consistent with an involvement of TNF-alpha in the reperfusion injury induced by myocardial ischaemia.
Analysis of Variance↗
Anti-phosphodiesterase activity of the coronary dilating agent hydrochloride carbocromene.
Explore the source record for details and available documents.
Animals↗
Observations on the effects of some antiaggregating drugs on platelet specific protein discharge after a very weak stimulus.
Platelet adhesion, aggregation, secretion, and survival have been shown to be changed in atherosclerosis disease and thromboembolic phenomena thus further increasing interest on antiaggregating drugs. In this paper we present some evidence that 8-chlorocarbochromen and carbochromen are significantly effective in preventing the discharge of platelet specific proteins from platelets subjects to a very weak stimulus while acetylsalicylic acid and aminophylline are ineffective in this regard.
Aminophylline↗
The increase of the openings of the surface-connected canalicular system in weakly stimulated platelets is prevented by a carbochromen derivative. A computerized morphometric analysis of freeze-etched human platelet plasma-membrane.
When thrombin is added to platelet rich plasma at very low concentrations (0.02 U/ml), platelets undergo an activation process. Under these conditions platelets discharge beta-thromboglobulin, platelet factor 4 and the "platelet derived growth factor". In this paper we present evidence that when human platelets are weakly stimulated with thrombin, the number of openings of the surface connected canalicular system (SCCS) increases. This was observed ultrastructurally by the freeze-etching technique. 8-chlorocarbochromen, an antiaggregating drug, seems to inhibit this increase.
Adult↗