PMID- 29663608
OWN - NLM
STAT- MEDLINE
DCOM- 20180612
LR  - 20180612
IS  - 1522-7278 (Electronic)
IS  - 1520-4081 (Linking)
VI  - 33
IP  - 6
DP  - 2018 Jun
TI  - The effects of hexachloronaphthalene on selected parameters of heme biosynthesis 
      and systemic toxicity in female wistar rats after 90-day oral exposure.
PG  - 695-705
LID - 10.1002/tox.22558 [doi]
AB  - Hexachloronaphthalenes (HxCNs) are the most toxic congeners of polychlorinated 
      naphthalenes, a group of compounds lately included into the list of persistent 
      organic pollutants (POPs). This study presents the effects of 90-day intragastric 
      administration of HxCN to female Wistar rats at doses of 0.03, 0.1, and 0.3 mg/kg 
      body weight. The study examined selected parameters of the heme synthesis 
      pathway, oxidative stress, hepatic cytochromes level, and basic hematology 
      indicators. A micronucleus test was also performed. The subchronic exposure of 
      rats to HxCN resulted in disruption of heme biosynthesis, hematological 
      disturbances, and hepatotoxicity. The highest dose of HxCN inhibited 
      aminolevulinic acid dehydratase (ALA-D) and uroporphyrinogen decarboxylase 
      (URO-D). Accumulation of higher carboxylated porphyrins in the liver and 
      increased excretion of 5-aminolevulinic acid in the urine was observed after a 
      dose of 0.1 mg/kg body weight. The most sensitive effect of HxCN in rats was very 
      strong induction of hepatic CYP1A1 activity, which was observed after the lowest 
      dose. The highest dose of HxCN induced significant thrombocytopenia, thymic 
      atrophy and hepatotoxicity, expressed as hepatomegaly and hepatic steatosis.
CI  - (c) 2018 Wiley Periodicals, Inc.
FAU - Klimczak, Michal
AU  - Klimczak M
AD  - Department of Toxicology, Faculty of Pharmacy, Medical University of Lodz, 
      Muszynskiego 1, Lodz, 90-151, Poland.
FAU - Darago, Adam
AU  - Darago A
AUID- ORCID: 0000-0002-1801-3227
AD  - Department of Toxicology, Faculty of Pharmacy, Medical University of Lodz, 
      Muszynskiego 1, Lodz, 90-151, Poland.
FAU - Bruchajzer, Elzbieta
AU  - Bruchajzer E
AD  - Department of Toxicology, Faculty of Pharmacy, Medical University of Lodz, 
      Muszynskiego 1, Lodz, 90-151, Poland.
FAU - Domeradzka-Gajda, Katarzyna
AU  - Domeradzka-Gajda K
AD  - Department of Toxicology and Carcinogenesis, Nofer Institute of Occupational 
      Medicine, Sw. Teresy 8, Lodz, 91-348, Poland.
FAU - Stepnik, Maciej
AU  - Stepnik M
AD  - Department of Toxicology and Carcinogenesis, Nofer Institute of Occupational 
      Medicine, Sw. Teresy 8, Lodz, 91-348, Poland.
FAU - Kuzajska, Katarzyna
AU  - Kuzajska K
AD  - Department of Toxicology, Faculty of Pharmacy, Medical University of Lodz, 
      Muszynskiego 1, Lodz, 90-151, Poland.
FAU - Kilanowicz, Anna
AU  - Kilanowicz A
AD  - Department of Toxicology, Faculty of Pharmacy, Medical University of Lodz, 
      Muszynskiego 1, Lodz, 90-151, Poland.
LA  - eng
PT  - Journal Article
DEP - 20180416
PL  - United States
TA  - Environ Toxicol
JT  - Environmental toxicology
JID - 100885357
RN  - 0 (Naphthalenes)
RN  - 42VZT0U6YR (Heme)
RN  - 58877-88-6 (1,2,3,4,5,6-hexachloronaphthalene)
RN  - EC 1.14.14.1 (Cytochrome P-450 CYP1A1)
RN  - EC 4.2.1.24 (Porphobilinogen Synthase)
SB  - IM
MH  - Administration, Oral
MH  - Animals
MH  - Cytochrome P-450 CYP1A1/metabolism
MH  - Female
MH  - Heme/*biosynthesis
MH  - Liver/drug effects/metabolism
MH  - Metabolic Networks and Pathways/drug effects
MH  - Naphthalenes/administration & dosage/*toxicity
MH  - Oxidative Stress/*drug effects
MH  - Porphobilinogen Synthase/metabolism
MH  - Rats
MH  - Rats, Wistar
MH  - Toxicity Tests, Chronic
OTO - NOTNLM
OT  - CYP1A1
OT  - heme biosynthesis
OT  - hexachloronaphthalene
OT  - rat
OT  - toxicity
EDAT- 2018/04/18 06:00
MHDA- 2018/06/13 06:00
CRDT- 2018/04/18 06:00
PHST- 2018/01/19 00:00 [received]
PHST- 2018/03/19 00:00 [revised]
PHST- 2018/03/25 00:00 [accepted]
PHST- 2018/04/18 06:00 [pubmed]
PHST- 2018/06/13 06:00 [medline]
PHST- 2018/04/18 06:00 [entrez]
AID - 10.1002/tox.22558 [doi]
PST - ppublish
SO  - Environ Toxicol. 2018 Jun;33(6):695-705. doi: 10.1002/tox.22558. Epub 2018 Apr 
      16.