diisononyl-phthalate and glyceryl-2-arachidonate

DiNP (Di-isononyl phthalate) has been recently introduced as DEHP (Bis (2-ethylhexyl) phthalate) substitute and due to its chemical properties, DiNP is commonly used in a large variety of plastic items. The endocannabinoid system (ECS) is a lipid signaling system involved in a plethora of physiological pathways including the control of the reproductive and metabolic processes. In this study, the effects of DiNP on the ECS of zebrafish (male and female) gonads were analyzed. Adult zebrafish were chronically exposed for 21 days via water to 3 environmentally relevant concentrations of DiNP (42 μg/L; 4.2 μg/L; 0.42 μg/L). In females, the Gonadosomatic Index (GSI) and the number of fertilized eggs were reduced by the lowest concentration of DiNP tested. The levels of two endocannabinoids, Anandamide (AEA) and 2-Arachidonoylglycerol (2-AG), were not affected, while a reduction of the N-oleoyl-ethanolamine (OEA) level was observed. Transcriptional changes were reported in relation to genes coding for the ECS receptors and the enzymes involved in the ECS pathway. DiNP exposure in males reduced the GSI as well as changed the levels of endocannabinoids. Moreover, DiNP treatment induced significative changes in the genes coding for the ECS receptors and enzymes, and significantly increased the activity of the fatty acid amide hydrolase (FAAH). In summary, in zebrafish, exposure to environmentally relevant concentrations of DiNP disrupted the ECS and affected reproduction in a gender specific manner.

Topics: Animals; Arachidonic Acids; Diethylhexyl Phthalate; Endocannabinoids; Female; Glycerides; Gonads; Male; Phthalic Acids; Polyunsaturated Alkamides; Reproduction; Toxicity Tests; Water Pollutants, Chemical; Zebrafish

Phthalates, used as plasticizers, have become a ubiquitous contaminant and have been reported for their potential to induce toxicity in living organisms. Among them, di-isononyl phthalate (DiNP) has been recently used to replace di(2-ethylhexyl) phthalate (DEHP). Nowadays, there is evidence that DiNP is an endocrine-disrupting chemical; 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, and 42 µg/L) of DiNP via water for 3 weeks. Afterwards, we investigated transcript levels for genes involved in the ECS of the brain and liver as well as liver histology and image analysis, Fourier-transform infrared spectroscopy imaging, and measurement of endocannabinoid levels. Our results demonstrate that DiNP upregulates orexigenic signals and causes hepatosteatosis together with deregulation of the 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.

Topics: Animals; Arachidonic Acids; Brain; Dose-Response Relationship, Drug; Endocannabinoids; Endocrine Disruptors; Fatty Liver; Female; Gene Expression; Glycerides; Lipid Metabolism; Lipoprotein Lipase; Liver; Phospholipase D; Phthalic Acids; Plasticizers; Polyunsaturated Alkamides; Receptor, Cannabinoid, CB1; Receptor, Cannabinoid, CB2; Zebrafish