ZFIN ID: ZDB-PUB-170923-2
Dose - specific effects of Di-isononyl phthalate on the endocannabinoid system and on liver of female zebrafish
Forner-Piquer, I., Maradonna, F., Gioacchini, G., Santangeli, S., Allarà, M., Piscitelli, F., Habibi, H.R., Di Marzo, V., Carnevali, O.
Date: 2017
Source: Endocrinology   158(10): 3462-3476 (Journal)
Registered Authors: Carnevali, Oliana
Keywords: none
MeSH Terms:
  • Animals
  • Arachidonic Acids/metabolism
  • Brain/drug effects*
  • Brain/metabolism
  • Dose-Response Relationship, Drug
  • Endocannabinoids/metabolism*
  • Endocrine Disruptors/pharmacology
  • Fatty Liver/metabolism
  • Female
  • Gene Expression/drug effects
  • Glycerides/metabolism
  • Lipid Metabolism/drug effects*
  • Lipoprotein Lipase/drug effects
  • Lipoprotein Lipase/genetics
  • Lipoprotein Lipase/metabolism
  • Liver/drug effects*
  • Phospholipase D/drug effects
  • Phospholipase D/genetics
  • Phospholipase D/metabolism
  • Phthalic Acids/pharmacology*
  • Plasticizers/pharmacology*
  • Polyunsaturated Alkamides/metabolism
  • Receptor, Cannabinoid, CB1/drug effects
  • Receptor, Cannabinoid, CB1/genetics
  • Receptor, Cannabinoid, CB1/metabolism
  • Receptor, Cannabinoid, CB2/drug effects
  • Receptor, Cannabinoid, CB2/genetics
  • Receptor, Cannabinoid, CB2/metabolism
  • Zebrafish
PubMed: 28938452 Full text @ Endocrinology
Phthalates, used as plasticizers, have become a ubiquitous contaminant and have been reported for their potential to induce toxicity in living organisms. Among them, the Di-isononyl phthalate (DiNP) has been recently used to replace the bis(2-ethylhexyl) phthalate (DEHP). Nowadays, there is evidence that DiNP is an Endocrine Disrupting Chemical (EDC), however little is known about its effects on the Endocannabinoid System (ECS) and lipid metabolism. Hence, the aim of our study was to investigate the effects of DiNP on the ECS in zebrafish liver and brain and on hepatic lipid storage. To do so, adult female zebrafish were exposed to three concentrations (0.42 µg/L; 4.2 µg/L; 42 µg/L) of DiNP via water for 3 weeks. Afterwards, we investigated transcript levels for genes involved in the ECS of brain and liver as well as liver histology and image analysis, Fourier-Transform Infrared Spectroscopy (FT-IR) imaging, and measurement of EC levels. Our results demonstrate that DiNP upregulates orexigenic signals and causes hepatosteatosis together with deregulation of peripheral ECS and lipid metabolism. A decrease in the levels of ECS components at the central level was observed after exposure to the highest DiNP concentration tested. These findings suggest that replacement of DEHP with DiNP should be considered with caution because of observed adverse DiNP effects on aquatic organisms.