ABSTRACT
Terbinafine is an antimycotic drug usually used against several superficial fungal infections and with a potential application in the treatment of human cancers. Since to date there are few data on the genotoxic effects of terbinafine in mammalian cells, current study evaluated the potential genotoxic of such antifungal agent in cultured human peripheral blood lymphocytes. Terbinafine was used at the peak plasma concentration (1.0 µg/ml) and in four additional concentrations higher than the human plasmatic peak (5.0 µg/ml, 25.0 µg/ml, 50.0 µg/ml and 100.0 µg/ml). Chromosomal aberrations (CA), sister chromatid exchanges (SCE), micronuclei (MN), nucleoplasmic bridges (NP) and nuclear buds (NB) were scored as genetic endpoints. In all analysis no significant differences (α = 0.05, Kruskal-Wallis test) were observed. Complementary criterion adopted to obtain the final response in cytogenetic agreed with statistical results. Therefore, results of this study showed that terbinafine neither induced CA, SCE, MN, NP and NB nor affected significantly mitotic, replication and cytokinesis-block proliferation indices in any of the tested concentrations. It may be assumed that terbinafine was not genotoxic or cytotoxic to cultured human peripheral blood lymphocytes in our experimental conditions.
Subject(s)
Antifungal Agents/toxicity , Lymphocytes/drug effects , Naphthalenes/toxicity , Adult , Cell Proliferation/drug effects , Cells, Cultured , Cytokinesis/drug effects , Female , Humans , Lymphocytes/pathology , Male , Micronuclei, Chromosome-Defective/chemically induced , Micronucleus Tests , Mitosis/drug effects , Risk Assessment , Sister Chromatid Exchange/drug effects , Terbinafine , Young AdultABSTRACT
Fatores ambientais e genéticos, ou mesmo ainteração destes, podem ser causadores da surdez sendo amesma o déficit sensorial mais frequente em humanos, sendoestimado que um a cada 500 recém-nascidos tenha perdaauditiva bilateral permanente, e que esta incidência aumentepara 3,5:1000 em indivíduos na adolescência. Determinadosfatores ambientais podem ser potencializados, quandodeterminadas mutações estão presentes no genoma. Éamplamente conhecida que a utilização de antibióticosaminoglicosídeos pode originar a surdez; especialmentequando o sujeito possuir mutações mitocondriaispredisponentes. A mutação C1494T do gene mitocondrial MTRNR1,o qual é responsável pela formação da subunidade12S do RNA ribossômico (12S rRNA), tem sido descritaassociada à perda auditiva pelo uso de antibióticosaminoglicosídeos. Objetivo: É o de investigar a prevalênciada mutação mitocondrial C1494T do gene MT-RNR1 em coortesde sujeitos ouvintes e surdos, das regiões Norte e Nordeste doEstado do Paraná, Brasil. Material e Método: Foraminvestigados 80 sujeitos ouvintes saudáveis e 80 surdos queapresentavam surdez pré-lingual, não sindrômica, de etiologiadesconhecida, sendo casos isolados dentro das famílias. Foiutilizada a técnica de PCR para amplificação da região, deum fragmento de 936 pb, na posição 1494, do gene MT-RNR1seguido de digestão pela enzima de restrição Hph I. Resultados:A mutação C1494T não foi encontrada nas amostras de sujeitosouvintes e de surdos. Conclusões: A mutação C1494T do geneMT-RNR1 pode ser considerada ausente ou rara nas populaçõesde sujeitos ouvintes e surdos das regiões Norte e Nordeste doestado do Paraná, Brasil...
Deafness is the most common sensory deficit inhumans, which may be caused by environmental and geneticfactors or even by a combination of both. It has been estimatedthat one in every 500 newborns has bilateral permanent hearingloss, and this incidence increases to 3.5:1,000 individuals inadolescence. Certain environmental factors may be enhancedwhen specific mutations are present in the genome. It is widelyknown that the use aminoglycoside antibiotics may lead tohearing loss, especially if the individual has predisposingmitochondrial mutations. Mutation C1494T of themitochondrial gene MT-RNR1 which causes the formation ofthe subunit 12S of the ribosome RNA (12S rRNA), has beenassociated with hearing loss due to the use of aminoglycosideantibiotics. Objective: This study investigates the occurrenceof mitochondrial mutation C1494T in the gene MT-RNR1 incohorts of hearing and deaf people in northern and northwesternregions of Paraná state, Brazil. Material and Methods: Eightyhearing people and eighty deaf people were analyzed. Thelatter were characterized as pre-lingual, non-syndromic, ofunknown etiology, being isolated cases within the family. PCRtechnique was used for amplification of the fragment 936 bpof the gene MT-RNR1 at position 1494, followed by digestionwith restriction enzyme Hph I. Results: Mutation C1494T wasnot detected in the samples of hearing and deaf people.Conclusions: Mutation C1494T of the gene MT-RNR1 may beabsent or rare in populations of hearing and deaf people innorthern and northwestern regions of Paraná state, Brazil...
