Disease relevance of Cignolin

• Dithranol for psoriasis [1].
• These retinoids also inhibited the appearance of papillomas in mouse epidermis in the two-stage tumorigenesis model using 7,12-dimethylbenz(a)anthracene (200 nmol) as the initiator and anthralin (444 nmol) as the promoter during the 32-week period of promotion [2].
• No parallel effect was observed for epidermal Langerhans (Ia+) cells, the second major epidermal immunofunctional cell type, except in the case of anthralin, a finding which is consistent with the reported toxicity of this agent [3].
• In the cyanobacterium Synechococcus PCC 6311 anthralin increases the pH gradient and decreases ATP levels [4].
• Finally, we have shown that hyperthermia and anthralin treatments are toxic for LC whereas they have little or no effect on keratinocyte viability [5].

Psychiatry related information on Cignolin

• Therefore, a high patient compliance can be obtained with the new dithranol formulation [6].

High impact information on Cignolin

• It is concluded that dithranol inflammation is initiated by formation of free radicals; these may act through lipid peroxidation and production of inflammatory endoperoxides or by a more direct mechanism [7].
• However, despite its superiority in terms of cost and patient acceptability, P.U.V.A. cannot be recommended as the first line of treatment for patients with uncomplicated, dithranol-responsive plaque psoriasis until there is more information on relapse-rate and toxicity [8].
• Inhibition by retinoids of anthralin-induced mouse epidermal ornithine decarboxylase activity and anthralin-promoted skin tumor formation [2].
• The skin tumor-promoting ability of 1,8-dihydroxy-3-methyl-9-anthrone (chrysarobin) was compared with that of 12-O-tetradecanoylphorbol-13-acetate (TPA) and 1,8-dihydroxy-9-anthrone (anthralin) in SENCAR mice [9].
• Maximal papilloma responses were achieved by 15 weeks of promotion with TPA whereas at least 25 weeks of promotion were necessary to achieve maximal papilloma responses with chrysarobin or anthralin indicating marked differences in tumor latency between the two classes of compounds [9].

Chemical compound and disease context of Cignolin

• Although dose-response comparisons indicated that chrysarobin was several orders of magnitude less potent than TPA for promoting papilloma formation, this anthrone was 1.5 to 2 times more potent than anthralin [9].
• The first papillomas appeared 8-11 weeks after initiation and the incidences of papillomas at the end of the experiment were 85% (dithranol 3.5 mM), 16% (butantrone 30 mM), 36% (10-isobutyryl dithranol 30 mM) and 50% (10-valeryl dithranol 30 mM) [10].
• Dithranol, with and without the addition of salicylic acid, was applied daily on normal skin according to a short contact protocol as used in the treatment of psoriasis [11].
• Topical treatment with dithranol, tar or wisely used corticosteroids is preferable to systemic treatment, except in severe forms of psoriasis where systemic corticosteroids or antimitotic drugs, especially methotrexate, may be necessary [12].
• Epidermal activity of NAD-dependent isocitrate dehydrogenase in psoriasis during treatment with dithranol [13].

Biological context of Cignolin

• Over a range of doses, three promoters (croton oil, 12-O-tetradecanoylphorbol-13-acetate, and anthralin) were found to inhibit DNA repair synthesis while their nonpromoting analogs (phorbol and 1,8-dihydroxyanthraquinone) had little effect [14].
• Iodoacetate, anthralin, and catechol potentiated UV-induced mitotic crossing-over, aberrant colony formation, and mutation, while catechol also increased UV-induced gene conversion [15].
• Two different lines of evidence show that ROIs, in particular H2O2, are second messengers for the anthralin-induced NF-(kappa)B activation [16].
• Reactive oxygen intermediates (ROIs) generated in vivo during the auto-oxidation of anthralin were discussed as mediators of the inflammatory response, but it is not yet understood how this is translated into novel inflammatory gene expression [16].
• An attempt was made to clarify the effect of anthralin on epidermal cell kinetics [17].

Anatomical context of Cignolin

• Anti-psoriatic drug anthralin activates transcription factor NF-kappa B in murine keratinocytes [16].
• Inhibition of leukotriene production persisted after washing of anthralin-treated neutrophils [18].
• In human keratinocytes oxygen metabolism is influenced by anthralin in a similar pattern as in isolated mitochondria, and ATP content is decreased [4].
• In contrast, lymphocyte proliferation was inhibited by only 50% at an anthralin concentration of 10 micrograms/ml [19].
• In particular, phenylacyl analogs were also 6 times more efficient in inhibition of lipid peroxidation in model membranes than anthralin [20].

Associations of Cignolin with other chemical compounds

• On the other hand, tumor-promoting agents such as anthralin, cantharidin, Tween 60, and tobacco leaf extract failed to induce plasminogen activator [21].
• Without initiation the incidences were 6 and 2% (dithranol), 2 and 2% (butantrone) and 2 and 0% (10-valeryl dithranol) in the 21- and 36-week studies, respectively [10].
• Alterations in the length of the dendritic processes of CD1+ cells were also induced, and semi-quantitative analysis revealed significant decreases in dendrite length in the reactions to sodium lauryl sulphate (p less than 0.05), nonanoic acid (p less than 0.001), croton oil (p less than 0.05), and dithranol (p less than 0.005) [22].
• When tested in homogenate with 4.5 microM arachidonic acid, anthralin specifically inhibited 12-HETE production with IC50 of 50.0 microM; no significant effect against cyclooxygenase was observed over the dose range of 2-200 microM [23].
• In contrast, anthralin, sodium dodecyl sulphate and acetic acid induced a similar degree of PGE2 release in human and rat keratinocyte cultures, but release was specifically associated with a cytotoxic response [24].

Gene context of Cignolin

• Anthralin decreases keratinocyte TGF-alpha expression and EGF-receptor binding in vitro [19].
• The results show a dose-dependent inhibition of MO IL-6, IL-8, and TNF-alpha release with a half-maximal inhibitory concentration of 0.25-0.6 microgram/ml of anthralin [25].
• Secretion of IL-1 beta immunoreactivity measured by ELISA as well as determination of biological activity of IL-1 using the D10[N4]M-bioassay revealed a slight increase in IL-1 secretion with a maximum at an anthralin concentration of 0.1 microgram/ml [25].
• RESULTS: Our results showed that dithranol treatment did not change the highly elevated level of interleukin-8 mRNA of HaCaT cells [26].
• Dithranol upregulates IL-10 receptors on the cultured human keratinocyte cell line HaCaT [26].

Analytical, diagnostic and therapeutic context of Cignolin

• Dithranol or photochemotherapy for psoriasis [27]?
• MALDI spectra of medium molar mass PET, representative of the entire molar mass distribution, were obtained only when a good solvent for PET was used, such as 1,1,1,3,3,3-hexafluoro-2-propanol (commonly referred to as HFIP), as the sample preparation solvent and dithranol as the matrix [28].
• Oral administration of 30 mg/kg TMK688, a dose which markedly inhibits tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA)-stimulated LTB4 formation in mouse skin, markedly inhibited both TPA-promoted and a non-TPA-type tumor promoter anthralin-promoted skin tumor formation in 7,12-dimethylbenz[a]anthracene (DMBA)-initiated CD-1 mice [29].
• Treatment of human skin in organ culture produced similar levels of adducts, while treatment with dithranol, a non-mutagenic therapeutic agent, resulted in chromatograms indistinguishable from those from untreated controls [30].
• These results are correlated with those obtained with intact whole human epidermis and suction blister fluid showing that, in the former case, anthralin binds to protein as suggested by absorption and fluorescence spectroscopies [31].

References