PMID- 33838175
OWN - NLM
STAT- MEDLINE
DCOM- 20210830
LR  - 20240402
IS  - 1873-6351 (Electronic)
IS  - 0278-6915 (Print)
IS  - 0278-6915 (Linking)
VI  - 152
DP  - 2021 Jun
TI  - Increased toxicity and retention of perflourooctane sulfonate (PFOS) in humanized 
      CYP2B6-Transgenic mice compared to Cyp2b-null mice is relieved by a high-fat diet 
      (HFD).
PG  - 112175
LID - S0278-6915(21)00208-8 [pii]
LID - 10.1016/j.fct.2021.112175 [doi]
AB  - PFOS is a persistent, fluorosurfactant used in multiple products. Murine Cyp2b's 
      are induced by PFOS and high-fat diets (HFD) and therefore we hypothesized that 
      human CYP2B6 may alleviate PFOS-induced steatosis. Cyp2b-null and hCYP2B6-Tg mice 
      were treated with 0, 1, or 10 mg/kg/day PFOS by oral gavage for 21-days while 
      provided a chow diet (ND) or HFD. Similar to murine Cyp2b10, CYP2B6 is inducible 
      by PFOS. Furthermore, three ND-fed hCYP2B6-Tg females treated with 10 mg/kg/day 
      PFOS died during the exposure period; neither Cyp2b-null nor HFD-fed mice died. 
      hCYP2B6-Tg mice retained more PFOS in serum and liver than Cyp2b-null mice 
      presumably causing the observed toxicity. In contrast, serum PFOS retention was 
      reduced in the HFD-fed hCYP2B6-Tg mice; the opposite trend observed in HFD-fed 
      Cyp2b-null mice. Hepatotoxicity biomarkers, ALT and ALP, were higher in 
      PFOS-treated mice and repressed by a HFD. However, PFOS combined with a HFD 
      exacerbated steatosis in all mice, especially in the hCYP2B6-Tg mice with 
      significant disruption of key lipid metabolism genes such as Srebp1, Pparg, and 
      Hmgcr. In conclusion, CYP2B6 is induced by PFOS but does not alleviate PFOS 
      toxicity presumably due to increased retention. CYP2B6 protects from 
      PFOS-mediated steatosis in ND-fed mice, but increases steatosis when co-treated 
      with a HFD.
CI  - Copyright (c) 2021 Elsevier Ltd. All rights reserved.
FAU - Hamilton, Matthew C
AU  - Hamilton MC
AD  - Environmental Toxicology Program, Clemson University, Clemson, SC, 29634, USA.
FAU - Heintz, Melissa M
AU  - Heintz MM
AD  - Environmental Toxicology Program, Clemson University, Clemson, SC, 29634, USA.
FAU - Pfohl, Marisa
AU  - Pfohl M
AD  - College of Pharmacy, University of Rhode Island, Kingston, RI, 02881, USA.
FAU - Marques, Emily
AU  - Marques E
AD  - College of Pharmacy, University of Rhode Island, Kingston, RI, 02881, USA.
FAU - Ford, Lucie
AU  - Ford L
AD  - College of Pharmacy, University of Rhode Island, Kingston, RI, 02881, USA.
FAU - Slitt, Angela L
AU  - Slitt AL
AD  - College of Pharmacy, University of Rhode Island, Kingston, RI, 02881, USA.
FAU - Baldwin, William S
AU  - Baldwin WS
AD  - Environmental Toxicology Program, Clemson University, Clemson, SC, 29634, USA. 
      Electronic address: baldwin@clemson.edu.
LA  - eng
GR  - P20 GM121342/GM/NIGMS NIH HHS/United States
GR  - P42 ES027706/ES/NIEHS NIH HHS/United States
GR  - R15 ES017321/ES/NIEHS NIH HHS/United States
PT  - Journal Article
DEP - 20210408
PL  - England
TA  - Food Chem Toxicol
JT  - Food and chemical toxicology : an international journal published for the British 
      Industrial Biological Research Association
JID - 8207483
RN  - 0 (Alkanesulfonic Acids)
RN  - 0 (Fluorocarbons)
RN  - 0 (Triglycerides)
RN  - 9H2MAI21CL (perfluorooctane sulfonic acid)
RN  - EC 1.14.14.1 (CYP2B6 protein, human)
RN  - EC 1.14.14.1 (Cytochrome P-450 CYP2B6)
SB  - IM
MH  - Alkanesulfonic Acids/*toxicity
MH  - Animals
MH  - Cytochrome P-450 CYP2B6/genetics/*metabolism
MH  - *Diet, High-Fat
MH  - Female
MH  - Fluorocarbons/*toxicity
MH  - Gene Expression/drug effects
MH  - Humans
MH  - Liver/drug effects/metabolism/pathology
MH  - Male
MH  - Mice, Transgenic
MH  - Non-alcoholic Fatty Liver Disease/chemically 
      induced/*metabolism/pathology/*prevention & control
MH  - Triglycerides/metabolism
PMC - PMC8154739
MID - NIHMS1693735
OTO - NOTNLM
OT  - CYP2B6
OT  - Cytochrome P450
OT  - Hepatotoxicity
OT  - Non-alcoholic fatty liver disease (NAFLD)
OT  - Perflourooctane sulfonate (PFOS)
OT  - Polyunsaturated fatty acids (PUFAs)
COIS- Declaration of interests The authors declare that they have no known competing 
      financial interests or personal relationships that could have appeared to 
      influence the work reported in this paper.
EDAT- 2021/04/11 06:00
MHDA- 2021/08/31 06:00
PMCR- 2022/06/01
CRDT- 2021/04/10 20:07
PHST- 2021/01/20 00:00 [received]
PHST- 2021/03/24 00:00 [revised]
PHST- 2021/03/30 00:00 [accepted]
PHST- 2021/04/11 06:00 [pubmed]
PHST- 2021/08/31 06:00 [medline]
PHST- 2021/04/10 20:07 [entrez]
PHST- 2022/06/01 00:00 [pmc-release]
AID - S0278-6915(21)00208-8 [pii]
AID - 10.1016/j.fct.2021.112175 [doi]
PST - ppublish
SO  - Food Chem Toxicol. 2021 Jun;152:112175. doi: 10.1016/j.fct.2021.112175. Epub 2021 
      Apr 8.