Involvement of oxidative stress in 4-vinylcyclohexene-induced toxicity in Drosophila melanogaster

Free Radic Biol Med. 2014 Jun:71:99-108. doi: 10.1016/j.freeradbiomed.2014.03.014. Epub 2014 Mar 26.


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 µM-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 (δ-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, δ-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.

Keywords: 4-Vinylcyclohexene; Antioxidants; Neurotoxicity; Oxidative stress; RT-PCR; mRNA gene expression; δ-ALA-D.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholinesterase / genetics
  • Acetylcholinesterase / metabolism
  • Animals
  • Behavior, Animal / drug effects
  • Catalase / genetics
  • Catalase / metabolism
  • Cyclohexenes / toxicity*
  • Drosophila Proteins / genetics*
  • Drosophila Proteins / metabolism
  • Drosophila melanogaster / drug effects*
  • Drosophila melanogaster / genetics
  • Drosophila melanogaster / growth & development
  • Drosophila melanogaster / metabolism
  • Female
  • Gene Expression Regulation / drug effects*
  • Glutathione Transferase / genetics
  • Glutathione Transferase / metabolism
  • Heat-Shock Proteins / genetics
  • Heat-Shock Proteins / metabolism
  • Male
  • Mitogen-Activated Protein Kinase 1 / genetics
  • Mitogen-Activated Protein Kinase 1 / metabolism
  • NF-E2-Related Factor 2 / genetics
  • NF-E2-Related Factor 2 / metabolism
  • Oxidation-Reduction
  • Oxidative Stress
  • Porphobilinogen Synthase / genetics
  • Porphobilinogen Synthase / metabolism
  • Reactive Oxygen Species / agonists*
  • Reactive Oxygen Species / metabolism
  • Superoxide Dismutase / genetics
  • Superoxide Dismutase / metabolism
  • Water Pollutants, Chemical / toxicity*


  • Cyclohexenes
  • Drosophila Proteins
  • Heat-Shock Proteins
  • NF-E2-Related Factor 2
  • Reactive Oxygen Species
  • Water Pollutants, Chemical
  • 4-vinylcyclohexene
  • Catalase
  • Superoxide Dismutase
  • Glutathione Transferase
  • Mitogen-Activated Protein Kinase 1
  • Acetylcholinesterase
  • Porphobilinogen Synthase