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Title: Clofibrate and gemfibrozil induce an embryonic malabsorption syndrome in zebrafish

Abstract

Nutrient availability is one of the major non-genetic factors determining embryonic growth and larval or fetal size. Due to the high human consumption of blood lipid regulators, fibrates have recently been reported as pollutants in rivers. Our study investigated the developmental toxicity of fibrates in zebrafish. Treatment with micromolar concentrations of clofibrate or gemfibrozil induced an embryonic malabsorption syndrome (EMS) with very little yolk consumption, resulting in small-sized larvae. This effect was reversible on removing the drug from the water. Clofibrate delayed hatching time and decreased the amount of oil red O lipid staining in the vasculature. It also induced higher density, round-shaped neuromuscular junctions associated with disorganization and less striation of muscular fibers, and pericardial edema, as well as impairing thyroid gland morphogenesis. acox1, apoa1 and mtp hybridization transcript signals were not affected in the yolk syncytial layer (YSL) after clofibrate exposure. Di-(2-ethylhexyl)-phthalate did not slow down yolk resorption, whereas brefeldin A induced EMS. These findings suggest that the inhibition of yolk sac resorption on exposure to fibrate is not at a pre-translational level or peroxisome proliferator-activated receptor alpha dependent and may be due to an inhibition of the YSL constitutive cell secretion. The effects of fibrates and themore » potential bioconcentration in eggs as well as the additive action of structurally related toxicants warrant an evaluation of the developmental impact of these compounds after long-term exposure at environmentally relevant concentrations. Fibrate-induced EMS in zebrafish seems useful for studying the morphogenetic consequences of impaired nutrient availability during the early stages of vertebrate development.« less

Authors:
 [1];  [2];  [3]
  1. Laboratory of Environmental Toxicology (UPC), CN150, 08220 Terrassa (Spain)
  2. Genomique et Physiologie des Poissons, Universite Bordeaux 1, UMR NuAGe, 33405 Talence (France)
  3. Genomique et Physiologie des Poissons, Universite Bordeaux 1, UMR NuAGe, 33405 Talence (France), E-mail: p.babin@gpp.u-bordeaux1.fr
Publication Date:
OSTI Identifier:
21140825
Resource Type:
Journal Article
Journal Name:
Toxicology and Applied Pharmacology
Additional Journal Information:
Journal Volume: 228; Journal Issue: 3; Other Information: DOI: 10.1016/j.taap.2007.11.016; PII: S0041-008X(07)00517-0; Copyright (c) 2007 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0041-008X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; BLOOD; DMSO; EDEMA; EGGS; ENDOPLASMIC RETICULUM; INHIBITION; LARVAE; LEAD SULFIDES; MORPHOGENESIS; PHOSPHATES; RECEPTORS; THYROID; THYROXINE; TRIGLYCERIDES; VEINS; WASTE WATER; WATER TREATMENT

Citation Formats

Raldua, Demetrio, Andre, Michele, and Babin, Patrick J. Clofibrate and gemfibrozil induce an embryonic malabsorption syndrome in zebrafish. United States: N. p., 2008. Web. doi:10.1016/j.taap.2007.11.016.
Raldua, Demetrio, Andre, Michele, & Babin, Patrick J. Clofibrate and gemfibrozil induce an embryonic malabsorption syndrome in zebrafish. United States. doi:10.1016/j.taap.2007.11.016.
Raldua, Demetrio, Andre, Michele, and Babin, Patrick J. Thu . "Clofibrate and gemfibrozil induce an embryonic malabsorption syndrome in zebrafish". United States. doi:10.1016/j.taap.2007.11.016.
@article{osti_21140825,
title = {Clofibrate and gemfibrozil induce an embryonic malabsorption syndrome in zebrafish},
author = {Raldua, Demetrio and Andre, Michele and Babin, Patrick J.},
abstractNote = {Nutrient availability is one of the major non-genetic factors determining embryonic growth and larval or fetal size. Due to the high human consumption of blood lipid regulators, fibrates have recently been reported as pollutants in rivers. Our study investigated the developmental toxicity of fibrates in zebrafish. Treatment with micromolar concentrations of clofibrate or gemfibrozil induced an embryonic malabsorption syndrome (EMS) with very little yolk consumption, resulting in small-sized larvae. This effect was reversible on removing the drug from the water. Clofibrate delayed hatching time and decreased the amount of oil red O lipid staining in the vasculature. It also induced higher density, round-shaped neuromuscular junctions associated with disorganization and less striation of muscular fibers, and pericardial edema, as well as impairing thyroid gland morphogenesis. acox1, apoa1 and mtp hybridization transcript signals were not affected in the yolk syncytial layer (YSL) after clofibrate exposure. Di-(2-ethylhexyl)-phthalate did not slow down yolk resorption, whereas brefeldin A induced EMS. These findings suggest that the inhibition of yolk sac resorption on exposure to fibrate is not at a pre-translational level or peroxisome proliferator-activated receptor alpha dependent and may be due to an inhibition of the YSL constitutive cell secretion. The effects of fibrates and the potential bioconcentration in eggs as well as the additive action of structurally related toxicants warrant an evaluation of the developmental impact of these compounds after long-term exposure at environmentally relevant concentrations. Fibrate-induced EMS in zebrafish seems useful for studying the morphogenetic consequences of impaired nutrient availability during the early stages of vertebrate development.},
doi = {10.1016/j.taap.2007.11.016},
journal = {Toxicology and Applied Pharmacology},
issn = {0041-008X},
number = 3,
volume = 228,
place = {United States},
year = {2008},
month = {5}
}