Diphenyl diselenide a janus-faced molecule

In this review, we summarized the potential role of synthetic organoseleno compounds as therapeutic or toxic agents, giving emphasis almost exclusively to diphenyl diselenide, the simplest of the diaryl diselenides, and some of its analogs. We presented the main molecular aspects related to the in vitro toxicity and pharmacology of diphenyl diselenide and also provided in vivo data indicating that the interaction of diphenyl diselenide with thiols can dictate either its toxicological or pharmacological property. The papers covered in this review indicate that a limited activation of the "toxic pathway", i.e., a controlled oxidation of specific high molecular weight thiol-containing molecules could contribute to the pharmacological effects of diphenyl diselenide. In conclusion, this review reinforces the necessity of developing new diorganoyl diselenides that could interact with specific molecular targets

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

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. Keywords: 4-Vinylcyclohexene 1,2-monoepoxide, 4-Vinylcyclohexene diepoxide, Reactive oxygen and nitrogen species, Changes in mRNA levels, Disruption of antioxidant homoeostasi