Protective effects of psoralen polymer lipid nanoparticles on doxorubicin - induced myocardial toxicity

Abstract Doxorubicin (DOX) induced myocardial toxicity may limit its therapeutic use in clinic. Psoralen (PSO), a major active tricyclic furocoumarin extracted from Psoralea corylifolia, is widely used as an antineoplastic agent in treatment of leukemia and other cancers. This study is aim to find the protective effect of psoralen polymer lipid nanoparticles (PSO-PLN) on doxorubicin-induced myocardial toxicity in mice. The model of myocardial toxicity induced by DOX was established. The experiment was divided into 6 groups: normal saline group, DOX + Sulfotanshinone Sodium, DOX + PSO-PLN (3 mg/kg), DOX + PSO-PLN (6 mg/kg), DOX + PSO-PLN (9 mg/ kg), DOX group. DOX alone treated mice lead to a significant decrease in the body weight, heart weight, and increase in the serum levels of lactate dehydrogenase (LDH), creatine kinase (CK) and malondialdehyde (MDA) markers of cardiotoxicity. However, DOX reduced glutathione (GSH) content and activities of antioxidant enzymes, including superoxide dismutase (SOD) and glutathione peroxidase (GPX), were recovered by PSO-PLN. And PSO-PLN also decreased markers of cardiotoxicity in the serum. Western blotting data showed that the protective effects of PSO-PLN might be mediated via regulation of protein kinase A (PKA) and p38. Our study suggest that PSO-PLN possesses antioxidant activities, inactivating PKA and p38 effect, which in turn protect the heart from the DOX-induced cardiotoxicity.

Psoralen inhibits malignant proliferation and induces apoptosis through triggering endoplasmic reticulum stress in human SMMC7721 hepatoma cells

BACKGROUND: Psoralen is a coumarin-like and coumarin-related benzofuran glycoside, which is a commonly used traditional Chinese medicine to treat patients with kidney and spleen-yang deficiency symptom. Psoralen has been reported to show estrogen-like activity, antioxidant activity, osteoblastic proliferation accelerating activity, antitumor effects and antibacterial activity. However, the antitumor mechanism of psoralen is not fully understood. This study aimed to investigate the therapeutic efficacy of psoralen in human hepatoma cell line SMMC7721 and the mechanism of antitumor effects. RESULTS: Psoralen inhibited proliferation of SMMC7721 in a dose- and time-dependent manner, and promoted apoptosis. Further, psoralen activated the ER stress signal pathway, including the expansion of endoplasmic reticulum, increasing the mRNA levels of GRP78, DDIT3, ATF4, XBP1, GADD34 and the protein levels of GDF15, GRP78, IRE1α, XBP-1s in a time-dependent manner. Psoralen induces cell cycle arrest at G1 phase by enhancing CyclinD1 and reducing CyclinE1 expression. Moreover, TUDC couldn't inhibit the psoralen-induced ER stress in SMMC7721 cells. CONCLUSIONS: Psoralen can inhibit the proliferation of SMMC7721 cells and induce ER stress response to induce cell apoptosis, suggesting that psoralen may represent a novel therapeutic option for the prevention and treatment hepatocellular carcinoma.

Comparación entre la efectividad del psoraleno más luz ultravioleta A (PUVA) y la luz ultravioleta B de banda estrecha (UVB-NB) en el tratamiento de la psoriasis / Comparison of the effectiveness of psoralen plus ultraviolet A light (PUVA) and ultraviolet B narrow band (UVB-NB) in the treatment of psoriasis

La psoriasis es una enfermedad inflamatoria crónica caracterizada por la hiperproliferación de queratinocitos como respuesta a la activación del sistema inmune. El manejo de esta patología es variado, pero las opciones terapéuticas disminuyen cuando la severidad aumenta, y hay que recurrir a medicaciones o terapias que traen mayores efectos secundarios no deseados. La fototerapia hace parte de los tratamientos utilizados en formas severas; la primera que se introdujo fue el uso de psoralenos más luz ultravioleta A (PUVA), pero es una terapia no del todo inocua que puede producir cataratas o inclusive cáncer de piel, lo que imposibilita su uso en algunos pacientes. Con el advenimiento de la terapia con luz ultravioleta B de banda estrecha (UVB-NB) en 1997, se abrió un nuevo espectro de alternativas de tratamiento para este tipo de pacientes, con similares características en cuanto a efectividad. Al comparar estos dos tipos de terapias, la literatura no es concluyente y deja un sinnúmero de dudas acerca de cuál de las dos terapias es más efectiva. Con la aparición de nuevas terapias, es importante conocer la más efectiva, pues son tratamientos menos costosos en comparación con los que están llegando al mercado.

Psoriasis is a chronic inflammatory disease characterized by keratinocyte hyperproliferation in response to activation of the immune system. The management of this condition is varied, but the therapeutic options decrease as the severity increases, and we must resort to medications or therapies that bring more unwanted side effects. Phototherapy is part of the treatments used in severe forms, the first to be introduced was the use of psoralen plus ultraviolet A light (PUVA), but it is not entirely safe therapy that can cause cataracts or even skin cancer, which precludes their use in some patients. With the advent of light therapy narrow band ultraviolet B (UVB-NB) in 1997, it opened a new spectrum of treatment alternatives for these patients, with similar characteristics in terms of effectiveness. By comparing these two types of therapies, the literature is not conclusive and leaves a host of questions about which of the two therapies is more effective. With the advent of new therapies, it is important to know the most effective, they are less expensive treatments compared with those who are coming to market.

Fotoferese extracorpórea / Extracorporeal photopheresis

Fotoferese extracorpórea é uma modalidade de terapia celular que tem demonstrado eficácia e segurança em pacientes portadores de doenças auto-imunes e mediadas por células T, incluindo esclerodermia, linfoma de células T cutâneo/ Síndrome de Sézary e doença enxerto-contra-hospedeiro após transplante de células-tronco hematopoiéticas. Tem sido empregada, ainda, com o intuito de induzir tolerância em transplantes de órgãos sólidos. O tratamento se baseia no efeito biológico de uma substância fotossensibilizante, o 8-metoxipsoraleno, e da radiação ultravioleta A, nas células mononucleares coletadas por aférese e reinfundidas ao paciente. O mecanismo de ação parece ser devido à indução de imunidade anticlonotípica direcionada a clones patogênicos de células T. O tratamento induz a apoptose de células T patogênicas, e a ativação de células apresentadoras de antígenos desempenha papel importante no processo imunomodulador.

Extracorporeal photopheresis is a method of cell therapy that has demonstrated efficacy in autoimmune diseases, cutaneous T-cell lymphoma/Sézary syndrome and graft-versus-host disease after hematopoietic stem-cell transplantation. This technique has also been employed as a treatment strategy to induce tolerance after solid organ transplants. Treatment is based on the biological effect of ultraviolet A radiation and a photosensitizing drug, 8-methoxypsoralen, on mononuclear cells collected by apheresis and reinfused into the patient. The suggested mechanism of action is related to the induction of anticlonotypic immunity directed against pathogenic clones of T lymphocytes. Treatment induces apoptosis of pathogenic T-cells, and it appears that activation of antigen-presenting cells has an important role in this process.

Terapia con baños de PUVA en eccema crónico / Therapy with PUVA baths in chronic eczemas

La terapia con PUVA tópica se ha usado desde la década de los 70 (1) en los países escandinavos y estados unidos, como una alternativa para disminuir los efectos adversos sistémicos de la terapia con PUVA oral, manteniendo la eficacia clínica. Los baños de PUVA son una excelente forma de PUVA tópica que permite una distribución homogénea del psoraleno, prácticamente sin exposición sistémica (2). Se ha usado en dermatosis tan variadas como la psoriasis, el liquen plano, el granuloma anular (3), el eccema crónico (4), el eccema atópico (5), la micosis fungoide, etc. Presentamos dos pacientes con eccema crónico refractario a tratamientos habituales que respondieron satisfactoriamente a los baños de PUVA

Alopecía areata: tratamiento / Alopecia areata: treatment

El tratamiento de la alopecía areata ha cambiado notablemente en la última década. Nuevas opciones terapéuticas están disponibles para los pacientes. Es deber del dermatólogo informar al paciente de todas las alternativas posibles para su caso, sus efectos colaterales y sus cifras de éxito. La decisión final es conjunta, entre el paciente, la familia del paciente (cuando corresponda) y el dermatólogo