title: Cytotoxic and genotoxic effects of acitretin, alone or in combination with psoralen-ultraviolet A or narrow-band ultraviolet B-therapy in psoriatic patients.
abstract: Acitretin is currently used alone or combined with PUVA (psoralen + UVA) or with narrow-band ultraviolet B (NBUVB), to treat moderate and severe psoriasis. However, little is known about the potential genotoxic/carcinogenic risk and the cytostatic/cytotoxic effects of these treatments. Our aim was to study the cytotoxic and genotoxic effects of acitretin - alone or in combination with PUVA or NBUVB - by performing studies with blood from patients with psoriasis vulgaris who were treated with acitretin, acitretin+PUVA or acitretin+NBUVB for 12 weeks, and in vitro studies with blood from healthy volunteers, which was incubated with acitretin at different concentrations. The cytotoxic and genotoxic effects were evaluated by the cytokinesis-blocked micronucleus test and the comet assay. Our results show that psoriatic patients treated with acitretin alone or with acitretin+NBUVB, did not show genotoxic effects. In addition, these therapies reduced the rate of proliferation and induced apoptosis and necrosis of lymphocytes; the same occurred with lymphocyte cultures incubated with acitretin (1.2-20μM). The acitretin+PUVA reduced also the proliferation rate, and increased the necrotic lymphocytes. Our studies suggest that therapy with acitretin alone or combined with NBUVB, as used in psoriatic patients, does not show genotoxic effects, reduces the rate of proliferation and induces apoptosis and necrosis of lymphocytes. The combination of acitretin with PUVA also reduces the proliferation rate and increases the number of necrotic lymphocytes. However, as it induced slight genotoxic effects, further studies are needed to clarify its genotoxic potential.
authors.affiliation: Laboratório de Bioquímica, Faculdade Farmácia, Universidade Coimbra, Coimbra, Portugal.
authors.forename: F S G
authors.initials: FS
authors.lastname: Silva
authors.forename: H
authors.initials: H
authors.lastname: Oliveira
authors.forename: A
authors.initials: A
authors.lastname: Moreiras
authors.forename: J C
authors.initials: JC
authors.lastname: Fernandes
authors.forename: E
authors.initials: E
authors.lastname: Bronze-da-Rocha
authors.forename: A
authors.initials: A
authors.lastname: Figueiredo
authors.forename: J B A
authors.initials: JB
authors.lastname: Custódio
authors.forename: P
authors.initials: P
authors.lastname: Rocha-Pereira
authors.forename: A
authors.initials: A
authors.lastname: Santos-Silva
mesh_terms: D017255:Acitretin / Q000008:administration & dosage / Q000627:therapeutic use / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D002455:Cell Division / Q000187:drug effects / Q000528:radiation effects; D003131:Combined Modality Therapy; D020552:Comet Assay; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005260:Female; D006801:Humans; D007641:Keratolytic Agents / Q000008:administration & dosage / Q000627:therapeutic use / Q000633:toxicity*; D008214:Lymphocytes / Q000187:drug effects* / Q000528:radiation effects; D008297:Male; D008730:Methoxsalen / Q000008:administration & dosage / Q000627:therapeutic use / Q000633:toxicity*; D015162:Micronucleus Tests; D008875:Middle Aged; D009336:Necrosis; D011701:PUVA Therapy / Q000009:adverse effects*; D011565:Psoriasis / Q000188:drug therapy*; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage / Q000627:therapeutic use / Q000633:toxicity*; D014466:Ultraviolet Rays / Q000009:adverse effects*
chemical_list: D007641:Keratolytic Agents; D011838:Radiation-Sensitizing Agents; D017255:Acitretin; D008730:Methoxsalen