Ovotoxicants 4-vinylcyclohexene 1,2-monoepoxide and 4-vinylcyclohexene diepoxide disrupt redox status and modify different electrophile sensitive target enzymes and genes in Drosophila melanogaster

Abstract

The compounds 4-vinylcyclohexene 1,2-monoepoxide (VCM) and 4-Vinylcyclohexene diepoxide (VCD) are the two downstream metabolites of 4-vinylcyclohexene (VCH), an ovotoxic agent in mammals. In addition, VCM and VCD may be found as by-products of VCH oxidation in the environment. Recently, we reported the involvement of oxidative stress in the toxicity of VCH in Drosophila melanogaster. However, it was not possible to determine the individual contributions of VCM and VCD in VCH toxicity. Hence, we investigated the toxicity of VCM and VCD (10–1000 µM) in flies after 5 days of exposure via the diet. Our results indicated impairments in climbing behaviour and disruptions in antioxidant balance and redox status evidenced by an increase in DCFH oxidation, decreases in total thiol content and glutathione-S-transferase (GST) activity in the flies exposed to VCM and VCD (p<0.05). These effects were accompanied by disruptions in the transcription of the genes encoding the proteins superoxide dismutase (SOD1), kelch-like erythroid-derived cap-n-collar (CNC) homology (ECH)-associated protein 1 (Keap-1), mitogen activated protein kinase 2 (MAPK-2), catalase, Cyp18a1, JAFRAC 1 (thioredoxin peroxidase 1) and thioredoxin reductase 1 (TrxR-1) (p<0.05). VCM and VCD inhibited acetylcholinesterase (AChE) and delta aminolevulinic acid dehydratase (δ-ALA D) activities in the flies (p<0.05). Indeed, here, we demonstrated that different target enzymes and genes were modified by the electrophiles VCM and VCD in the flies. Thus, D. melanogaster has provided further lessons on the toxicity of VCM and VCD which suggest that the reported toxicity of VCH may be mediated by its transformation to VCM and VCD.

Effect of dietary inclusions of bitter kola seed on geotactic behavior and oxidative stress markers in Drosophila melanogaster

“…The two main lines of defense against oxidative stress are endogenous antioxidant molecules (Abolaji, Kamdem, & Lugokenski, 2015) and repair enzymes that remove or repair oxidatively damaged macromolecules. Also, living organisms can withstand damages caused by oxidative stress in reaction to pro‐oxidants through the process of adaptive response (Crawford & Davies, 1994).…”

“…Reactive oxygen species (ROS) are harmful molecules, capable of inducing oxidative damage in amino acids, proteins, lipids, and DNA components of tissues at higher levels (Sharma, 2015;Valko, Rhodes, Moncol, Izakovic, & Mazur, 2006). The two main lines of defense against oxidative stress are endogenous antioxidant molecules (Abolaji, Kamdem, & Lugokenski, 2015) and repair enzymes that remove or repair oxidatively damaged macromolecules. Also, living organisms can withstand damages caused by oxidative stress in reaction to pro-oxidants through the process of adaptive response (Crawford & Davies, 1994).…”

4-Vinylcyclohexene diepoxide disrupts sperm characteristics, endocrine balance and redox status in testes and epididymis of rats

“…The fine balance between reactive oxygen species (ROS) production and scavenging by endogenous antioxidants are of utmost importance for testicular function. Interestingly, elevated levels of reactive oxygen and nitrogen species production with concomitant disruption of the antioxidant system in Drosophila melanogaster exposed to VCH and VCD have been reported by our research group [12,13]. In addition, we recently reported that, exposure to VCD-induced oxidative stress, resulting in hepatic and renal oxidative damage in male and female rats [10].…”

Geotactical and Neurochemical Phenotypes of Drosophila Melanogaster Following Nigella Sativa Exposure

“…Male and female wild type Drosophila melanogaster (Harwich strains) were acquired from the Drug Metabolism and Molecular Toxicology Research Laboratory, Department of Biochemistry, University of Ibadan, Ibadan, Nigeria. The culture and feeding medium, which was largely cornmeal based, was hygienically adopted from protocols reported by Abolaji et al (Abolaji et al, 2015). The flies were maintained under a cool and regulated temperature (23 ± 3°C), 60% humidity and natural day/night cycles in the Neurophytotherapy Lab (NPTL), Department of Anatomy, Olabisi Onabanjo University, Sagamu, Nigeria.…”