Dithranol: A Review of the Mechanism of Action in the Treatment of Psoriasis vulgaris

Kemény, Lajos; Ruzicka, Thomas; Braun‐Falco, Otto

doi:10.1159/000210836

Cited by 103 publications

(71 citation statements)

References 95 publications

(140 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The disease is of great concern due to its incurable nature (Schon and Boehncke, 2005;Lowes et al, 2007). Dithranol (1,8-dihydroxy-9-anthrone), also referred to as anthralin, is one of the crucial topical antipsoriatic drugs (Kemeny et al, 1990;Pavithran, 2001). It is a very effective compound in the treatment of active psoriasis, but its molecular mechanism of action is still not well understood.…”

Section: Introductionmentioning

confidence: 99%

Effects of the antipsoriatic drug dithranol on E2A and caspase-9 gene expression in vitro

Ronpirin¹,

Tencomnao²

2012

Genet. Mol. Res.

View full text Add to dashboard Cite

ABSTRACT. Although the precise causes of psoriasis remain to be elucidated, psoriasis has been known as a disorder in which factors in the immune system, enzymes and other biochemical substances that regulate skin cell division are functionally imbalanced, thereby resulting in rapid proliferation of keratinocytes and incomplete keratinization. The expression of candidate genes such as E2A and caspase-9, which have been recognized to play a critical role in cellular proliferation/ differentiation and apoptosis, is of great interest. They may be therapeutically targeted by the antipsoriatic drug, dithranol. We examined the molecular effects of dithranol on the mRNA and protein expression levels of E2A and caspase-9 in the HaCaT keratinocyte cell line. The HaCaT cells were treated with 0-0.5 µg/mL dithranol for 30 min. After dithranol was washed out, the HaCaT cells were cultured for 2 h, and their total cellular RNA and proteins were isolated. Quantitative realtime reverse transcriptase-polymerase chain reaction and Western blot were performed to determine the mRNA and protein levels of these two genes. We found that dithranol treatment in the range of 0.25-0.5 µg/ mL slightly upregulated the mRNA expression of E2A and caspase-9 approximately 1.5-and 1.2-fold, respectively. However, undetectable Expression of E2A and caspase-9 gene in response to dithranol change and minor downregulation of the protein expression levels were observed for E2A and caspase-9, respectively. Consequently, these genes appear not to be viable therapeutic targets for dithranol.

show abstract

Section: Introductionmentioning

confidence: 99%

Effects of the antipsoriatic drug dithranol on E2A and caspase-9 gene expression in vitro

Ronpirin¹,

Tencomnao²

2012

Genet. Mol. Res.

View full text Add to dashboard Cite

show abstract

“…Although anthralin displays effective therapeutic properties, the use of the drug is often limited by severe inflammation of perilesional, uninvolved skin. The therapeutic and toxic effects of anthralin are thought to be mediated by reactive oxygen species (ROS), including superoxide and hydroxyl radicals [2], as well as pro-oxidant anthralin metabolites [3]. In addition to anthralin, other common proinflammatory dermatotoxicants, including ultraviolet (UV) radiation and benzene are associated with free radical generation [4].…”

Section: Introductionmentioning

confidence: 99%

Antioxidants attenuate anthralin-induced skin inflammation in BALB/c mice: role of specific proinflammatory cytokines

Lange

Germolec

Foley

et al. 1998

Journal of Leukocyte Biology

View full text Add to dashboard Cite

Anthralin is the most common therapeutic agent among a small number of pro-oxidant, 9-anthrones effective in the topical treatment of psoriasis. However, the usefulness of this drug is diminished by toxic side effects, including skin irritation and inflammation. The activities of anthralin are believed to be mediated by the generation of reactive oxygen intermediates and anthrone radicals produced in the skin. In this study, the dermal inflammatory response to anthralin was determined using a mouse ear swelling test. Maximum ear swelling induced by anthralin coincided with the elevation of cytokine mRNA expression in the skin, including interleukin-6, granulocyte-macrophage colony-stimulating factor, macrophage inflammatory protein-2, and tumor necrosis factor ␣ at 24 h post challenge. The role of free radical generation in ear swelling and cytokine modulation were examined by systemic administration of cell permeable and impermeable antioxidants before anthralin challenge. Superoxide dismutase and ␣-tocopherol acetate, but not the glutathione precursor N-acetyl cysteine, were effective inhibitors of anthralininduced ear swelling and cytokine elevation. Maximum inflammatory cell infiltration occurred 72-96 h post anthralin challenge and was also reduced by antioxidants. These data suggest that oxidative stress, generated at the site of anthralin treatment, alters the expression of dermal chemokines and other cytokines resulting in the recruitment of inflammatory cells. Systemic antioxidant administration may provide opportunities for therapeutic intervention against anthralin-associated toxicities.

show abstract

“…In their course, initially asymptomatic clinical events precede immune cells migration to the skin and the response from keratinocytes [1].…”

Section: The Importance Of Specific Immune Mechanismsmentioning

confidence: 99%

“…The process of epidermal hyperproliferation is associated with an increased number of cell divisions in the basal layer and abnormal keratinocyte maturation cycle [1]. The clinical manifestations of the disease are different and may include single papules and plaques, larger patches or generalized changes (psoriatic erythroderma) [2].…”

mentioning

confidence: 99%

See 1 more Smart Citation

Psoriasis as a disease associated with the immune system disorders

Chomiczewska-Skóra¹,

Trznadel-Grodzka²,

Rotsztejn³

2013

cejoi

View full text Add to dashboard Cite

show abstract

Dithranol: A Review of the Mechanism of Action in the Treatment of Psoriasis vulgaris

Cited by 103 publications

References 95 publications

Effects of the antipsoriatic drug dithranol on E2A and caspase-9 gene expression in vitro

Effects of the antipsoriatic drug dithranol on E2A and caspase-9 gene expression in vitro

Antioxidants attenuate anthralin-induced skin inflammation in BALB/c mice: role of specific proinflammatory cytokines

Psoriasis as a disease associated with the immune system disorders

Contact Info

Product

Resources

About