Disease relevance of Cloricromene

• Effects of cloricromene, a coumarin derivative, on endotoxin-induced uveitis in Lewis rats [1].
• 6. Radiographic signs of protection against bone resorption and osteophyte formation were present in the joints of cloricromene-treated rat [2].
• Cloricromene reduces myocardial infarct size in rabbits when administered during the early reperfusion period [3].
• We investigated the effect of cloricromene in a rat model of periodontitis [4].
• Cloricromene in endotoxemia: role of NF-kappaB [5].

High impact information on Cloricromene

• The degree of staining for P-selectin, ICAM-1, nitrotyrosine, and PARS was markedly reduced in tissue sections obtained from LPS-recipient rats that had received cloricromene [1].
• The degree of staining for iNOS, COX-2, nitrotyrosine and PARS were markedly reduced in tissue sections obtained from collagen-treated rats, which had received cloricromene [2].
• 7. This study provides the first evidence that cloricromene, a coumarine derivative, attenuates the degree of chronic inflammation and tissue damage associated with collagen-induced arthritis in the rat [2].
• 6. The incorporation of [3H]-acetate into [3H]-PAF induced by serum-treated zymosan in human PMNs was also inhibited concentration-dependently by cloricromene, with an IC50 of 105 microM [6].
• 6. When monocyte adhesion was mediated by a large set of adhesive receptors, as obtained after treatment of HUVEC with either interleukin 1 beta (IL-1; 50 ng ml-1) or tumour necrosis factor-alpha (TNF; 100 u ml-1), the inhibitory effect of cloricromene was considerably reduced [7].

Chemical compound and disease context of Cloricromene

• Multiple actions of the coumarine derivative cloricromene and its protective effects on ischemic brain injury [8].

Biological context of Cloricromene

• 2. We have assessed the effects of cloricromene on (a) ex vivo platelet aggregation, and (b) infarct size using a model of myocardial ischaemia in the anaesthetized rabbit [9].
• 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 [10].
• 3. In vivo administration of cloricromene (2 mg kg-1, i.v.), an inhibitor of TNF-alpha biosynthesis, increased survival, enhanced mean arterial blood pressure and reduced macrophage and serum levels of TNF-alpha [11].
• Furthermore the in vitro effect of cloricromene on peritoneal macrophage phagocytosis and TNF-alpha release by primed peritoneal macrophages was investigated [12].
• Cloricromene inhibited both types of cell motility induced by FMLP in a concentration-dependent fashion [13].

Anatomical context of Cloricromene

• 4. Inhibition was maximal after 1 min of exposure of monocytes to cloricromene and persisted even in the absence of the drug [7].
• 6. While area at risk was similar for all groups studied, cloricromene (30 or 300 micrograms kg-1 min-1) or ibuprofen caused a reduction in infarct size, and decreased myeloperoxidase activity in the tissue of the infarcted myocardium [9].
• Inhibition of human monocyte adhesion to endothelial cells by the coumarin derivative, cloricromene [7].
• Cloricromene inhibits the activation of platelets and polymorphonuclear leukocytes (PMN) induced by specific stimuli [14].
• The purpose of this work was to characterize the mechanism of cloricromene-induced inhibition of TNF-alpha in rat macrophages [15].

Associations of Cloricromene with other chemical compounds

• After oral administration of cloricromene to a rabbit, plasma and platelets were taken at different times and cloricromene acid was then isolated by solid-phase extraction with Sep-Pak C18 cartridges using acetonitrile-tetrahydrofuran-20% aqueous acetic acid (15:11:74, v/v/v) as eluent [16].
• Eudragit RL100 nanoparticle system for the ophthalmic delivery of cloricromene [17].
• Pentoxifylline, cloricromene and SKF86002, when given intraperitoneally 2 h before challenge, produced 45, 52 and 61% reductions, respectively, in plasma levels of TNF alpha at 2.5 h post-injection with killed GBS (P < 0.05) [18].
• The direct addition of cloricromene in vitro to myocardial homogenates did not reduce hydroperoxide-induced chemiluminescence [19].

Gene context of Cloricromene

• Cloricromene treatment was associated with a minor body weight loss (p < 0.025) and significantly reduced tissue concentrations of MPO and TNF-alpha (p < 0.02, both) [20].
• The macroscopic damage scores, colon wet weights, and tissue MIP-2 levels were significantly increased in untreated and in cloricromene-treated rats compared with controls [20].
• 5. Both basal and chemoattractant-mediated monocyte adhesion was inhibited by cloricromene as it was by TS1/18, a monoclonal antibody (mAb) directed to beta 2 integrins; however, cytofluorimetric analysis showed that cloricromene was unable to modulate the expression of beta 2 integrins on the monocyte surface [7].
• The pharmacokinetics of a lipophilic alkylamino acid (LAA) prodrug of cloricromene (AD6), name CLOR-C4, was studied in rat plasma and brain [21].
• The effects of cloricromene on plasma endothelin-1 (ET-1) levels and on microcirculatory function in 9 patients with peripheral atherosclerotic arteriopathy (PAA) and in healthy control subjects were studied [22].

Analytical, diagnostic and therapeutic context of Cloricromene

• After a single oral administration of 8-chlorocarbochromen, a reduction of the high number of these openings has been observed [10].
• HPLC measurement showed that cloricromene accumulated in PMN within a few minutes and levels of the drug were still high after 60 min [13].
• A total of 159 patients with IC, Stage II (Fontaine), were enrolled in a double-blind, randomized, prospective, multicenter study comparing cloricromene (100 mg orally b.i.d.) or an identical placebo for 6 months [23].
• In contrast, cloricromene produced a significant improvement in the postischemic perfusion index and in recovery time in arteriopathic patients [22].
• 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) [24].

References