PMID- 32417428
OWN - NLM
STAT- MEDLINE
DCOM- 20200723
LR  - 20200723
IS  - 1879-3169 (Electronic)
IS  - 0378-4274 (Linking)
VI  - 331
DP  - 2020 Oct 1
TI  - Comparative toxicity analysis of corannulene and benzo[a]pyrene in mice.
PG  - 130-142
LID - S0378-4274(20)30135-1 [pii]
LID - 10.1016/j.toxlet.2020.05.002 [doi]
AB  - Increasing production of corannulene (COR), a non-planar polycyclic aromatic 
      hydrocarbon (PAH) with promising applications in many fields, has raised a 
      concern about its potential toxic effects. However, no study has been undertaken 
      to evaluate its metabolism and toxicity in mammals. In this study, the acute 
      toxicities of COR in mice were compared with benzo[apyrene (BaP), a typical 
      planar PAH with almost the same molecular weight. After 3-day exposures, the 
      concentrations of COR in both plasma and tissues of mice were higher than that of 
      BaP. However, blood chemistry and tissue weight monitoring showed no observable 
      toxicities in COR-exposed mice. Compared to BaP, exposure to COR resulted in less 
      activation of the aryl hydrocarbon receptor (AhR) and thus less induction of 
      hepatic cytochrome P450 1A(CYP1A) enzymes, which play a critical role in 
      metabolism of both COR and BaP. Additionally, COR also elicited less oxidative 
      stress and microbiota alteration in the intestine than did BaP. RNA-seq analysis 
      revealed that liver transcriptomes are responsive to COR and BaP, with less 
      alterations observed in COR-exposed mice. Unlike BaP, exposure to COR had no 
      effects on hepatic lipid and xenobiotic metabolism pathways. Nonetheless, COR 
      appeared to alter the mRNA expressions of genes involved in carcinogenicity, 
      oxidative stress, and immune-suppression. To conclude, this study for the first 
      time unveils a comparative understanding of the acute toxic effects of COR to BaP 
      in mice, and provides crucial insights into the future safety assessment of COR.
CI  - Copyright (c) 2020 Elsevier B.V. All rights reserved.
FAU - Li, Gentao
AU  - Li G
AD  - School of Pharmaceutical Science and Technology, Tianjin University, Tianjin, 
      300072, China.
FAU - Xiong, Hui
AU  - Xiong H
AD  - School of Pharmaceutical Science and Technology, Tianjin University, Tianjin, 
      300072, China.
FAU - Saeed, Khawar
AU  - Saeed K
AD  - School of Pharmaceutical Science and Technology, Tianjin University, Tianjin, 
      300072, China.
FAU - Ma, Ruicong
AU  - Ma R
AD  - School of Pharmaceutical Science and Technology, Tianjin University, Tianjin, 
      300072, China.
FAU - Xing, Yufeng
AU  - Xing Y
AD  - School of Pharmaceutical Science and Technology, Tianjin University, Tianjin, 
      300072, China.
FAU - Bi, Yajuan
AU  - Bi Y
AD  - School of Pharmaceutical Science and Technology, Tianjin University, Tianjin, 
      300072, China.
FAU - Li, Caiyu
AU  - Li C
AD  - School of Pharmaceutical Science and Technology, Tianjin University, Tianjin, 
      300072, China.
FAU - Huang, Jianhui
AU  - Huang J
AD  - School of Pharmaceutical Science and Technology, Tianjin University, Tianjin, 
      300072, China.
FAU - Zhang, Youcai
AU  - Zhang Y
AD  - School of Pharmaceutical Science and Technology, Tianjin University, Tianjin, 
      300072, China. Electronic address: youcai.zhang@tju.edu.cn.
LA  - eng
PT  - Journal Article
DEP - 20200515
PL  - Netherlands
TA  - Toxicol Lett
JT  - Toxicology letters
JID - 7709027
RN  - 0 (Polycyclic Aromatic Hydrocarbons)
RN  - 0 (Receptors, Aryl Hydrocarbon)
RN  - 0 (corannulene)
RN  - 3417WMA06D (Benzo(a)pyrene)
RN  - EC 1.14.14.1 (Cytochrome P-450 CYP1A1)
RN  - EC 1.14.14.1 (Cytochrome P-450 CYP1A2)
RN  - EC 1.15.1.1 (Superoxide Dismutase)
SB  - IM
MH  - Administration, Oral
MH  - Animals
MH  - Benzo(a)pyrene/pharmacokinetics/*toxicity
MH  - Cytochrome P-450 CYP1A1/biosynthesis
MH  - Cytochrome P-450 CYP1A2/biosynthesis
MH  - Injections, Intraperitoneal
MH  - Intestines/*drug effects/pathology
MH  - Liver/*drug effects/metabolism/pathology
MH  - Liver Function Tests
MH  - Male
MH  - Mice, Inbred C57BL
MH  - Organ Size/drug effects
MH  - Polycyclic Aromatic Hydrocarbons/blood/pharmacokinetics/*toxicity
MH  - Rats, Sprague-Dawley
MH  - Receptors, Aryl Hydrocarbon/*metabolism
MH  - Superoxide Dismutase/blood
MH  - Tissue Distribution
OTO - NOTNLM
OT  - Aryl hydrocarbon receptor
OT  - Benzo[a]pyrene
OT  - Corannulene
OT  - Polycyclic aromatic hydrocarbon
COIS- Declaration of Competing Interest We declare that we do not have any commercial 
      or associative interest that represents a conflict of interest in connection with 
      the work submitted.
EDAT- 2020/05/18 06:00
MHDA- 2020/07/24 06:00
CRDT- 2020/05/18 06:00
PHST- 2020/01/31 00:00 [received]
PHST- 2020/04/27 00:00 [revised]
PHST- 2020/05/03 00:00 [accepted]
PHST- 2020/05/18 06:00 [pubmed]
PHST- 2020/07/24 06:00 [medline]
PHST- 2020/05/18 06:00 [entrez]
AID - S0378-4274(20)30135-1 [pii]
AID - 10.1016/j.toxlet.2020.05.002 [doi]
PST - ppublish
SO  - Toxicol Lett. 2020 Oct 1;331:130-142. doi: 10.1016/j.toxlet.2020.05.002. Epub 
      2020 May 15.