RESUMO
Kaposi sarcoma herpesvirus (KSHV), also known as human herpesvirus 8, is the causative agent of Kaposi sarcoma; this malignant angiosarcoma is usually treated with conventional antitumor agents that can control disease evolution, but do not clear the latent KSHV episome that binds to cellular DNA. Some commercial antibacterial sulfonamides were tested for the ability to suppress latent KSHV. Quantitative PCR (qPCR) and cytofluorometry assays were used for detecting both viral DNA and the latency factor LANA (latency-associated nuclear antigen) in BC3 cells, respectively. The capacity of sulfonamides to impair MDM2-p53 complex formation was detected by an enzyme-linked immunosorbent assay method. The analysis of variance was performed according to one-way analysis of variance with Fisher as a post hoc test. Here we show that sulfonamide antibiotics are able to suppress the KSHV latent state in permanently infected BC3 lymphoma cells and interfere with the formation of the MDM2-p53 complex that KSHV seemingly needs to support latency and to trigger tumor cell transformation. These findings detected a new molecular target for the activity of sulfonamides and offer a new potential perspective for treating KSHV-induced lymphoproliferative diseases.
Assuntos
Antibacterianos/farmacologia , Antivirais/farmacologia , Herpesvirus Humano 8/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-mdm2/antagonistas & inibidores , Sulfonamidas/farmacologia , Proteína Supressora de Tumor p53/antagonistas & inibidores , Antibacterianos/efeitos adversos , Antígenos Virais/metabolismo , Antivirais/efeitos adversos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Transformação Celular Neoplásica/efeitos dos fármacos , Transformação Celular Viral/efeitos dos fármacos , Células Cultivadas , DNA Viral/metabolismo , Herpesvirus Humano 8/crescimento & desenvolvimento , Herpesvirus Humano 8/metabolismo , Células Endoteliais da Veia Umbilical Humana/citologia , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/metabolismo , Células Endoteliais da Veia Umbilical Humana/virologia , Humanos , Concentração Inibidora 50 , Proteínas Nucleares/metabolismo , Multimerização Proteica/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-mdm2/química , Proteínas Proto-Oncogênicas c-mdm2/genética , Proteínas Proto-Oncogênicas c-mdm2/metabolismo , Proteínas Recombinantes de Fusão/química , Proteínas Recombinantes de Fusão/metabolismo , Sulfaguanidina/efeitos adversos , Sulfaguanidina/farmacologia , Sulfametoxazol/efeitos adversos , Sulfametoxazol/farmacologia , Sulfanilamida , Sulfanilamidas/efeitos adversos , Sulfanilamidas/farmacologia , Sulfatiazol , Sulfatiazóis/efeitos adversos , Sulfatiazóis/farmacologia , Sulfonamidas/efeitos adversos , Proteína Supressora de Tumor p53/química , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismoRESUMO
INTRODUCTION: Fixed drug eruption is a lesion induced by drugs. The family of drugs usually incriminated are sulfonamides, tetracyclines and pyrazols. We describe nine cases of fixed drug eruption induced by sulfaguanidine, a sulfonamide with local action. CASE REPORTS: All the patients presented one or more fixed drug eruption reactivation lesions induced by sulfaguanidine as self-medication for diarrhea. The number of lesions increased in 7 cases after reactivation. The delay in occurrence of the fixed drug eruption decreased during the different episodes. The lesions predominated on the hands in 8 cases of 9. DISCUSSION: The sulfaguanidine must be added to the list of drug-induced fixed drug eruptions with limited absorption from the gastrointestinal tract.
Assuntos
Anti-Infecciosos/efeitos adversos , Toxidermias/etiologia , Eritema/induzido quimicamente , Sulfaguanidina/efeitos adversos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Toxidermias/patologia , Eritema/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeAssuntos
Angioedema/induzido quimicamente , Toxidermias/etiologia , Dermatoses Faciais/induzido quimicamente , Ácido Glicirretínico/efeitos adversos , Administração Oral , Benzocaína/efeitos adversos , Clorexidina , Combinação de Medicamentos , Feminino , Ácido Glicirretínico/administração & dosagem , Humanos , Pessoa de Meia-Idade , Estomatite/induzido quimicamente , Sulfaguanidina/efeitos adversos , Comprimidos , Tirotricina/efeitos adversosRESUMO
We report a patient who developed a fixed drug eruption (FDE) due to sulfaguanidine. This drug has not been previously implicated as a cause of FDE. The diagnosis was confirmed by an oral provocation and a biopsy of the lesion. Oral provocations with other sulfonamides, sulfamethoxazole and sulfadiazine, were well tolerated.