PMID- 15036755
OWN - NLM
STAT- MEDLINE
DCOM- 20040406
LR  - 20161124
IS  - 0300-483X (Print)
IS  - 0300-483X (Linking)
VI  - 196
IP  - 1-2
DP  - 2004 Mar 1
TI  - Effects of human pharmaceuticals on cytotoxicity, EROD activity and ROS 
      production in fish hepatocytes.
PG  - 41-55
AB  - Pharmaceuticals are found in the aquatic environment but their potential effects 
      on non-target species like fish remain unknown. This in vitro study is a first 
      approach in the toxicity assessment of human drugs on fish. Nine pharmaceuticals 
      were tested on two fish hepatocyte models: primary cultures of rainbow trout 
      hepatocytes (PRTH) and PLHC-1 fish cell line. Cell viability, interaction with 
      cytochrome P450 1A (CYP1A) enzyme and oxidative stress were assessed by using 
      3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrasodium bromide tetrazolium (MTT), 
      7-ethoxyresorufin-o-deethylase (EROD) and dichlorofluorescein (DCFH-DA) assays, 
      respectively. The tested drugs were clofibrate (CF), fenofibrate (FF), 
      carbamazepine (CBZ), fluoxetine (FX), diclofenac (DiCF), propranolol (POH), 
      sulfamethoxazole (SFX), amoxicillin (AMX) and gadolinium chloride (GdCl(3)). All 
      substances were cytotoxic, except AMX at concentration up to 500 microM. The 
      calculated MTT EC(50) values ranged from 2 microM (CF) to 651 microM (CBZ) in 
      PLHC-1, and from 53 microM (FF) to 962 microM (GdCl(3)) in PRTH. CF, FF, and FX 
      were the most cytotoxic drugs and induced oxidative stress before being 
      cytotoxic. Compared to hepatocytes from human and dog, fish hepatocytes seemed to 
      be more susceptible to the peroxisome proliferators (PPs) CF and FF. In PLHC-1 
      cells none of the tested drugs induced the EROD activity whereas POH appeared as 
      a weak EROD inducer in PRTH. Moreover, in PRTH, SFX, DiCF, CBZ and to a lesser 
      extend, FF and CF inhibited the basal EROD activity at clearly sublethal 
      concentrations which may be of concern at the biological and chemical levels in a 
      multipollution context.
FAU - Laville, N
AU  - Laville N
AD  - Unite d'Evaluation des Risques Ecotoxicologiques, INERIS, BP 2, Parc 
      Technologique Alata, DRC/Ecotoxicology group, F60550 Verneuil-en-Halatte, France. 
      nathalie.laville-etudiant@ineris.fr
FAU - Ait-Aissa, S
AU  - Ait-Aissa S
FAU - Gomez, E
AU  - Gomez E
FAU - Casellas, C
AU  - Casellas C
FAU - Porcher, J M
AU  - Porcher JM
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Ireland
TA  - Toxicology
JT  - Toxicology
JID - 0361055
RN  - 0 (Pharmaceutical Preparations)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Tetrazolium Salts)
RN  - 0 (Thiazoles)
RN  - 0 (Water Pollutants, Chemical)
RN  - EC 1.14.14.1 (Cytochrome P-450 CYP1A1)
RN  - EUY85H477I (thiazolyl blue)
SB  - IM
MH  - Animals
MH  - Cell Line
MH  - Cell Separation
MH  - Cell Survival/drug effects
MH  - Cells, Cultured
MH  - Cytochrome P-450 CYP1A1/*metabolism
MH  - Hepatocytes/*drug effects/enzymology
MH  - Humans
MH  - Oncorhynchus mykiss/*metabolism
MH  - *Pharmaceutical Preparations
MH  - Reactive Oxygen Species/*metabolism
MH  - Tetrazolium Salts
MH  - Thiazoles
MH  - Water Pollutants, Chemical/*toxicity
EDAT- 2004/03/24 05:00
MHDA- 2004/04/07 05:00
CRDT- 2004/03/24 05:00
PHST- 2003/07/18 00:00 [received]
PHST- 2003/11/03 00:00 [revised]
PHST- 2003/11/03 00:00 [accepted]
PHST- 2004/03/24 05:00 [pubmed]
PHST- 2004/04/07 05:00 [medline]
PHST- 2004/03/24 05:00 [entrez]
AID - S0300483X03005018 [pii]
AID - 10.1016/j.tox.2003.11.002 [doi]
PST - ppublish
SO  - Toxicology. 2004 Mar 1;196(1-2):41-55. doi: 10.1016/j.tox.2003.11.002.