TY - JOUR
T1 - Effects of the lipid regulator drug gemfibrozil
T2 - a toxicological and behavioral perspective
AU - Henriques, Jorge F.
AU - Almeida, Ana Rita
AU - Andrade, Thayres
AU - Koba, Olga
AU - Golovko, Oksana
AU - Soares, Amadeu M.V.M.
AU - Oliveira, Miguel
AU - Domingues, Inês
N1 - Funding Information:
Koba, Golovko—Support was also given by the Ministry of Education, Youth and Sports of the Czech Republic —projects “CENAKVA” (No. CZ.1.05/2.1.00/01.0024) and “CENAKVA II“ (No. LO1205 under the NPU I program), by the Grant Agency of the University of South Bohemia in Ceske Budejovice (No. 018/2014/Z ) and by the Czech Science Foundation (No. P503/11/1130 ).
Funding Information:
This work was supported by European Funds through COMPETE and by National Funds through the Portuguese Science Foundation (FCT) within projects CLIMATOX (PTDC/AAG-GLO/4059/2012) and PEst-C/MAR/LA0017/2013, and the Post-Doc grant (SFRH/BPD/90521/2012) attributed to Inês Domingues. Support was also given by the Post-Doc grant (SFRH/BPD/85107/2012) attributed to Miguel Oliveira.
Publisher Copyright:
© 2015 Elsevier B.V.
PY - 2016/1/1
Y1 - 2016/1/1
N2 - Pharmaceuticals are emerging contaminants as their worldwide consumption increases. Fibrates such as gemfibrozil (GEM) are used in human medicine to reduce blood concentrations of cholesterol and triacylglycerol and also are some of the most frequently reported pharmaceuticals in waste waters and surface waters. Despite some studies have already demonstrated the negative impact in physiological and/or reproductive endpoints in adult fish, data on survival and behavioral effects in fish larvae are lacking. This study aimed to assess the effects of GEM on zebrafish eleutheroembryo development and locomotor behavior. A fish embryo toxicity (FET) test was undertaken to evaluate GEM acute toxicity by exposing embryos to 0, 6.58, 9.87, 14.81, 22.22, 33.33 and 50mg/L. Developmental endpoints such as hatching success, edemas and malformations were recorded. A second test was undertaken by exposing embryos to 0, 1.5, 3 and 6mg/L in order to evaluate the effects of GEM on 120 and 144h post fertilization (hpf) larvae locomotor activity by video tracking, using a Zebrabox® (Viewpoint, France) device. From the data recorded, several parameters such as total swimming distance (TSD) and total swimming time (TST) in each 120s integration time were calculated. Data showed that this compound has a moderate toxic effect on fish embryo development, affecting both survival and hatching success with a calculated 96h LC50 of 11.01mg/L and no effects at the developmental level at 6mg/L. GEM seems to impair locomotor activity, even at concentrations where developmental abnormalities were unperceived, at concentrations as low as 1.5mg/L. Both TSD and TST were sensitive to GEM exposure. These effects do not seem to be independent of the developmental stage as 120hpf larvae seem to present a development bias with repercussions in locomotor behavior. This study highlights the need to include behavioral endpoints in ecotoxicological assays as this seems to be a more sensitive endpoint often disregarded.
AB - Pharmaceuticals are emerging contaminants as their worldwide consumption increases. Fibrates such as gemfibrozil (GEM) are used in human medicine to reduce blood concentrations of cholesterol and triacylglycerol and also are some of the most frequently reported pharmaceuticals in waste waters and surface waters. Despite some studies have already demonstrated the negative impact in physiological and/or reproductive endpoints in adult fish, data on survival and behavioral effects in fish larvae are lacking. This study aimed to assess the effects of GEM on zebrafish eleutheroembryo development and locomotor behavior. A fish embryo toxicity (FET) test was undertaken to evaluate GEM acute toxicity by exposing embryos to 0, 6.58, 9.87, 14.81, 22.22, 33.33 and 50mg/L. Developmental endpoints such as hatching success, edemas and malformations were recorded. A second test was undertaken by exposing embryos to 0, 1.5, 3 and 6mg/L in order to evaluate the effects of GEM on 120 and 144h post fertilization (hpf) larvae locomotor activity by video tracking, using a Zebrabox® (Viewpoint, France) device. From the data recorded, several parameters such as total swimming distance (TSD) and total swimming time (TST) in each 120s integration time were calculated. Data showed that this compound has a moderate toxic effect on fish embryo development, affecting both survival and hatching success with a calculated 96h LC50 of 11.01mg/L and no effects at the developmental level at 6mg/L. GEM seems to impair locomotor activity, even at concentrations where developmental abnormalities were unperceived, at concentrations as low as 1.5mg/L. Both TSD and TST were sensitive to GEM exposure. These effects do not seem to be independent of the developmental stage as 120hpf larvae seem to present a development bias with repercussions in locomotor behavior. This study highlights the need to include behavioral endpoints in ecotoxicological assays as this seems to be a more sensitive endpoint often disregarded.
KW - Developmental abnormalities
KW - Gemfibrozil
KW - Lipid regulator
KW - Sub-lethal
KW - Swimming behavior
KW - Zebrafish
UR - http://www.scopus.com/inward/record.url?scp=84950335882&partnerID=8YFLogxK
U2 - 10.1016/j.aquatox.2015.09.017
DO - 10.1016/j.aquatox.2015.09.017
M3 - Article
C2 - 26482382
SN - 0166-445X
VL - 170
SP - 355
EP - 364
JO - Aquatic Toxicology
JF - Aquatic Toxicology
ER -
