PMID- 20936652
OWN - NLM
STAT- MEDLINE
DCOM- 20110809
LR  - 20211203
IS  - 1099-1263 (Electronic)
IS  - 0260-437X (Print)
IS  - 0260-437X (Linking)
VI  - 31
IP  - 3
DP  - 2011 Apr
TI  - Toxicity and recovery in the pregnant mouse after gestational exposure to the 
      cyanobacterial toxin, cylindrospermopsin.
PG  - 242-54
LID - 10.1002/jat.1586 [doi]
AB  - Cylindrospermopsin (CYN) is a tricyclic alkaloid toxin produced by fresh water 
      cyanobacterial species worldwide. CYN has been responsible for both livestock and 
      human poisoning after oral exposure. This study investigated the toxicity of CYN 
      to pregnant mice exposed during different segments of gestation. The course of 
      recovery and individual responses to the toxin were evaluated. Adverse effects of 
      CYN were monitored up to 7 weeks post-dosing by clinical examination, 
      histopathology, biochemistry and gene expression. Exposure on gestational days 
      (GD) 8-12 induced significantly more lethality than GD13-17 exposure. 
      Periorbital, gastrointestinal and distal tail hemorrhages were seen in both 
      groups. Serum markers indicative of hepatic injury (alanine amino transferase, 
      aspartate amino transferase and sorbitol dehydrogenase) were increased in both 
      groups; markers of renal dysfunction (blood urea nitrogen and creatinine) were 
      elevated in the GD8-12 animals. Histopathology was observed in the liver 
      (centrilobular necrosis) and kidney (interstitial inflammation) in groups 
      exhibiting abnormal serum markers. The expression profiles of genes involved in 
      ribosomal biogenesis, xenobiotic and lipid metabolism, inflammatory response and 
      oxidative stress were altered 24 h after the final dose. One week after dosing, 
      gross, histological and serum parameters had returned to normal, although 
      increased liver/body weight ratio and one instance of gastrointestinal bleeding 
      was found in the GD13-17 group. Gene expression changes persisted up to 2 weeks 
      post-dosing and returned to normal by 4 weeks. Responses of individual animals to 
      CYN exposure indicated highly significant inter-animal variability within the 
      treated groups.
CI  - Copyright (c) 2010 John Wiley & Sons, Ltd.
FAU - Chernoff, N
AU  - Chernoff N
AD  - US EPA, ORD, National Health and Environmental Effects Research Laboratory, 
      Research Triangle Park, NC 27711, USA. chernoff.neil@epa.gov
FAU - Rogers, E H
AU  - Rogers EH
FAU - Zehr, R D
AU  - Zehr RD
FAU - Gage, M I
AU  - Gage MI
FAU - Malarkey, D E
AU  - Malarkey DE
FAU - Bradfield, C A
AU  - Bradfield CA
FAU - Liu, Y
AU  - Liu Y
FAU - Schmid, J E
AU  - Schmid JE
FAU - Jaskot, R H
AU  - Jaskot RH
FAU - Richards, J H
AU  - Richards JH
FAU - Wood, C R
AU  - Wood CR
FAU - Rosen, M B
AU  - Rosen MB
LA  - eng
GR  - R01 ES012752-01/ES/NIEHS NIH HHS/United States
GR  - P30 CA014520/CA/NCI NIH HHS/United States
GR  - ES012752/ES/NIEHS NIH HHS/United States
GR  - CA014520/CA/NCI NIH HHS/United States
GR  - P30 CA014520-299026/CA/NCI NIH HHS/United States
GR  - R01 ES012752/ES/NIEHS NIH HHS/United States
GR  - ImNIH/Intramural NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, N.I.H., Intramural
DEP - 20101008
PL  - England
TA  - J Appl Toxicol
JT  - Journal of applied toxicology : JAT
JID - 8109495
RN  - 0 (Alkaloids)
RN  - 0 (Bacterial Toxins)
RN  - 0 (Biomarkers)
RN  - 0 (Cyanobacteria Toxins)
RN  - 0 (Water Pollutants, Chemical)
RN  - 2JIZ556BA3 (cylindrospermopsin)
RN  - 56HH86ZVCT (Uracil)
SB  - IM
MH  - Alkaloids/*toxicity
MH  - Animals
MH  - Bacterial Toxins
MH  - Biomarkers/blood
MH  - *Cyanobacteria
MH  - Cyanobacteria Toxins
MH  - Embryo Loss/chemically induced
MH  - Embryo, Mammalian/*drug effects
MH  - Female
MH  - Fetal Death/chemically induced
MH  - Gene Expression/drug effects
MH  - Hemorrhage/chemically induced
MH  - Kidney/drug effects/metabolism
MH  - Liver/drug effects/metabolism
MH  - Maternal Exposure/*adverse effects
MH  - Mice
MH  - Necrosis/chemically induced/pathology
MH  - Nephritis, Interstitial/chemically induced/pathology
MH  - Organ Size/drug effects
MH  - Pregnancy
MH  - Prenatal Exposure Delayed Effects/chemically induced/pathology
MH  - Recovery of Function
MH  - Uracil/*analogs & derivatives/toxicity
MH  - Water Pollutants, Chemical/*toxicity
PMC - PMC3020984
MID - NIHMS230620
EDAT- 2010/10/12 06:00
MHDA- 2011/08/10 06:00
PMCR- 2012/04/01
CRDT- 2010/10/12 06:00
PHST- 2010/05/11 00:00 [received]
PHST- 2010/07/20 00:00 [revised]
PHST- 2010/07/28 00:00 [accepted]
PHST- 2010/10/12 06:00 [entrez]
PHST- 2010/10/12 06:00 [pubmed]
PHST- 2011/08/10 06:00 [medline]
PHST- 2012/04/01 00:00 [pmc-release]
AID - 10.1002/jat.1586 [doi]
PST - ppublish
SO  - J Appl Toxicol. 2011 Apr;31(3):242-54. doi: 10.1002/jat.1586. Epub 2010 Oct 8.