Journal
FREE RADICAL BIOLOGY AND MEDICINE
Volume 71, Issue -, Pages 99-108Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.freeradbiomed.2014.03.014
Keywords
4-Vinylcyclohexene; Oxidative stress; mRNA gene expression; RT-PCR; Antioxidants; delta-ALA-D; Neurotoxicity
Funding
- TWAS-CNPq
- CNPq
- CAPES
- FAPERGS
- FAPERGS-PRONEX
- FAPERGS-PRONEX-CNPq
- VITAE Fundation
- Rede Brasileira de Neurociencias (IBNET-FINEP)
- FINEP-CTINFRA
- INCT-CNPq
- CNPQ-Institute
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4-Vinylcyclohexene (VCH) is a dimer of 1,3-butadiene produced as a by-product of pesticides, plastic, rubber, flame retardants, and tire production. Although, several studies have reported the ovotoxicity of VCH, information on a possible involvement of oxidative stress in the toxicity of this occupational chemical is scarce. Hence, this study was carried out to investigate further possible mechanisms of toxicity of VCH with a specific emphasis on oxidative stress using a Drosophila melanogaster model. D. melanogaster (both genders) of 1 to 3 days old were exposed to different concentrations of VCH (10 mu M-1 mM) in the diet for 5 days. Subsequently, the survival and negative geotaxis assays and the quantification of reactive oxygen species (ROS) generation were determined. In addition, we evaluated RT-PCR expressions of selected oxidative stress and antioxidant mRNA genes (HSP27, 70, and 83, SOD, Nrf-2, MAPK2, and catalase). Furthermore, catalase, glutathione-S-transferase (GST), delta aminolevulinic acid dehydratase (delta-ALA-D), and acetylcholinesterase (AChE) activities were determined. VCH exposure impaired negative geotaxic behavior and induced the mRNA of SOD, Nrf-2, and MAPK2 genes expressions. There were increases in catalase and ROS production, as well as inhibitions of GST, 5-ALA-D, and AChE activities (P<0.05). Our results suggest that the VCH mechanism of toxicity is associated with oxidative damage, as evidenced by the alteration in the oxidative stress-antioxidant balance, and possible neurotoxic consequences due to decreased AChE activity, and impairments in negative geotaxic behavior. Thus, we conclude that D. melanogaster is a useful model for investigating the toxicity of VCH exposure, and here, we have provided further insights on the mechanism of VCH-induced toxicity. (C) 2014 Elsevier Inc. All rights reserved.
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