Abstract
BackgroundExposure to dichlorvos (DDVP), an organophosphorus pesticide, is known to result in neurotoxicity as well as other metabolic perturbations. However, the molecular causes of DDVP toxicity are poorly understood, especially in cells other than neurons and muscle cells. To obtain a better understanding of the process of non-neuronal DDVP toxicity, we exposed zebrafish to different concentrations of DDVP, and investigated the resulting changes in liver histology and gene transcription.ResultsFunctional enrichment analysis of genes affected by DDVP exposure identified a number of processes involved in energy utilization and stress response in the liver. The abundance of transcripts for proteins involved in glucose metabolism was profoundly affected, suggesting that carbon flux might be diverted toward the pentose phosphate pathway to compensate for an elevated demand for energy and reducing equivalents for detoxification. Strikingly, many transcripts for molecules involved in β-oxidation and fatty acid synthesis were down-regulated. We found increases in message levels for molecules involved in reactive oxygen species responses as well as ubiquitination, proteasomal degradation, and autophagy.To ensure that the effects of DDVP on energy metabolism were not simply a consequence of poor feeding because of neuromuscular impairment, we fasted fish for 29 or 50 h and analyzed liver gene expression in them. The patterns of gene expression for energy metabolism in fasted and DDVP-exposed fish were markedly different.ConclusionWe observed coordinated changes in the expression of a large number of genes involved in energy metabolism and responses to oxidative stress. These results argue that an appreciable part of the effect of DDVP is on energy metabolism and is regulated at the message level. Although we observed some evidence of neuromuscular impairment in exposed fish that may have resulted in reduced feeding, the alterations in gene expression in exposed fish cannot readily be explained by nutrient deprivation.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-015-1941-2) contains supplementary material, which is available to authorized users.
Highlights
Exposure to dichlorvos (DDVP), an organophosphorus pesticide, is known to result in neurotoxicity as well as other metabolic perturbations
A number of prior studies have investigated the effects of dichlorvos on particular aspects of liver metabolism, they focused on particular metabolites or enzymes [25, 26]
While a number of prior studies described the effects of DDVP exposure on hepatic metabolism [25, 26], they focused on particular metabolites and/or the activities of particular enzymes
Summary
Exposure to dichlorvos (DDVP), an organophosphorus pesticide, is known to result in neurotoxicity as well as other metabolic perturbations. The molecular causes of DDVP toxicity are poorly understood, especially in cells other than neurons and muscle cells. Dichlorvos (DDVP), an organophosphorus pesticide used for indoor insect and livestock parasite control, is among the most common commercially available pesticides. There are, significant concerns over its acute and chronic toxicity [1,2,3], especially because dichlorvos is relatively stable in water, soil, and air [4], DDVP reversibly inhibits acetyl cholinesterase (AChE) activity leading to an accumulation of acetylcholine and increased cholinergic activity in the central and peripheral nervous system, and at neuromuscular junctions [3, 4]. In neuronal tissue of rats, DDVP exposure alters carbohydrate homeostasis [8, 9]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
