Influência dos polimorfismos da glutationa s-transferase na ototoxicidade dos aminoglicosídeos

Abstract

The process of hair cell damage and death as a result of exposure to noise and ototoxins seems to be mediated by reactive oxygen species.Aim: To investigate the relationship between genetic polymorphisms in the Glutathione S-transferase and the susceptibility to hearing loss induced by aminoglycosides. Materials and Methods:Null genotypes were analyzed by multiplex-PCR in the DNA samples from 50 patients and 72 controls. The patients were divided into 3 groups, 10 with hearing loss using aminoglycosides (group A), 20 with hearing loss without exposure to the drug (group B) and 20 hearing individuals who used the antibiotic (group C). Study Design: Experimental.Results: Polymorphisms in the GSTM1 and GSTT1 genes were found in 16% and 42% of patients and in 18% and 53% of the control group, respectively. After statistical analysis no significant difference was observed between the control groups and A (p=0.86) and (p=0.41), controls and B (p=0.27) and (p=0.24), controls and C (p=0.07) and (p=0.47), controls and A + C (p=0.09) and (p=0.47), C and A (p=0.32) and (p=0.75), GSTT1 and GSTM1, respectively. Conclusion:Our data show that polymorphisms in GSTM1 and GSTT1 genes have no influence on the ototoxicity of aminoglycosides. Braz J Otorhinolaryngol. 2010;76(3):306-9. ORIGINAL ARTICLE BJORL

Intracellular mechanisms of aminoglycoside-induced cytotoxicity

“…133 Cellular enzymes with antioxidant properties, such as superoxide dismutases and glutathione S-transferase, could also be used to reduce ROS levels. 134–136 …”

“…133 Cellular enzymes with antioxidant properties, such as superoxide dismutases and glutathione S-transferase, could also be used to reduce ROS levels. [134][135][136] Clinical interventions to interfere with aminoglycoside binding to phosphoinositides, RNA or proteins are far from established, partly because our understanding of these cytotoxicity mechanisms remains insufficient to devise a pharmacological strategy. However, in vitro studies and research on animal models are steadily accumulating evidence that support a few promising approaches to reduce aminoglycoside toxicity.…”

Avaliação De Estresse Oxidativo No Plasma De Bovinos Leiteiros Com Mastite

“…Dados in vivo revelam que esse fármaco também aumenta os níveis de lipídeos oxidados (29,30) . Ademais, segundo Lopez-Novoa et al (31) e Quiros et al (32) , a gentamicina pode interagir com a mitocôndria, ativando a via intrínseca da apoptose e interferindo com o funcionamento da cadeia respiratória, o que compromete a produção de ATP e contribui para a geração de ERs.…”

Association of GST gene polymorphism and noise-induced hearing loss<em>Running title: GST gene polymorphism and NIHL</em>

“…However in much more comprehensive study among 10% most susceptible and 10% most resistant to noise subjects selected from 1200 Swedish workers, an association between GSTT1, GSTM1, and GSTP1 could not be confirmed [11]. Palodetto et al found no significant association between GST gene variants (GSTT1 and GSTM1) and ototoxicity of aminoglycosides, which seems to involve similar oxidative stress mechanisms [16]. In addition to contradictory results in various studies, the effect of genetic factors on susceptibility of NIHL can only be regarded as valid when they have been replicated in an independent population [17]; so, the present study investigates the association between the deletion polymorphism in the GSTT1 (rs1049055) and GSTM1 (rs10712361) genes and susceptibility to NIHL in Iranian population.…”