PMID- 35934180
OWN - NLM
STAT- MEDLINE
DCOM- 20220908
LR  - 20220921
IS  - 1879-3185 (Electronic)
IS  - 0300-483X (Linking)
VI  - 478
DP  - 2022 Aug
TI  - Oxidative stress and Cx43-mediated apoptosis are involved in PFOS-induced 
      nephrotoxicity.
PG  - 153283
LID - S0300-483X(22)00195-0 [pii]
LID - 10.1016/j.tox.2022.153283 [doi]
AB  - Perfluorooctane sulfonate (PFOS) is a persistent organic pollutant that can cause 
      nephrotoxicity. However, the underlying mechanisms are not fully understood and 
      require further investigation. In the present study, we established a 
      PFOS-exposed Sprague-Dawley (SD) rat kidney injury model by intraperitoneal 
      injection of PFOS (1 mg/kg and 10 mg/kg body weight) every alternate day for 15 
      days and cytotoxicity models of normal rat kidney epithelial (NRK52E) and human 
      renal proximal tubular (HK2) cells exposed to PFOS (20 muM and 60 muM) for 24 h to 
      reveal the mechanisms underlying PFOS-induced nephrotoxicity. Data showed that 
      PFOS increased the kidney index and induced nephrotoxicity in rats. Furthermore, 
      PFOS significantly increased malondialdehyde (MDA) levels, decreased GSH 
      peroxidase (GSH-PX) activity in kidney tissues, and increased intracellular 
      reactive oxygen species (ROS) levels in NRK52E and HK2 cells. Following PFOS 
      treatment, mitochondrial damage in the renal tubular epithelial cells of rats was 
      observed and the mitochondrial membrane potential (DeltaPsim) was decreased in NRK52E 
      cells. PFOS upregulated apoptosis of tubular epithelial cells and expression of 
      Connexin 43 (Cx43) in vitro and in vivo. The Cx43 inhibitor gap26 attenuated the 
      apoptosis of tubular epithelial cells. In conclusion, our findings reveal that 
      PFOS may trigger renal tubular cell apoptosis through oxidative stress and 
      upregulation of Cx43, resulting in PFOS-induced nephrotoxicity.
CI  - Copyright (c) 2022 The Authors. Published by Elsevier B.V. All rights reserved.
FAU - Tang, Leilei
AU  - Tang L
AD  - Department of Pharmacy, Affiliated Xiaoshan Hospital, Hangzhou Normal University, 
      Hangzhou 311200, China.
FAU - Yu, Jiawen
AU  - Yu J
AD  - Department of Pharmacy, Affiliated Xiaoshan Hospital, Hangzhou Normal University, 
      Hangzhou 311200, China.
FAU - Zhuge, Sheng
AU  - Zhuge S
AD  - Department of Surgery, Liangzhu Hospital of Yuhang District, Hangzhou 311113, 
      China.
FAU - Chen, Hangping
AU  - Chen H
AD  - Department of Pharmacy, Affiliated Xiaoshan Hospital, Hangzhou Normal University, 
      Hangzhou 311200, China.
FAU - Zhang, Lingdi
AU  - Zhang L
AD  - Department of Pharmacy, Affiliated Xiaoshan Hospital, Hangzhou Normal University, 
      Hangzhou 311200, China.
FAU - Jiang, Guojun
AU  - Jiang G
AD  - Department of Pharmacy, Affiliated Xiaoshan Hospital, Hangzhou Normal University, 
      Hangzhou 311200, China. Electronic address: jguojun999@163.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20220805
PL  - Ireland
TA  - Toxicology
JT  - Toxicology
JID - 0361055
RN  - 0 (Alkanesulfonic Acids)
RN  - 0 (Antioxidants)
RN  - 0 (Connexin 43)
RN  - 0 (Fluorocarbons)
RN  - 0 (Reactive Oxygen Species)
RN  - 9H2MAI21CL (perfluorooctane sulfonic acid)
SB  - IM
MH  - Alkanesulfonic Acids
MH  - Animals
MH  - Antioxidants/metabolism
MH  - Apoptosis
MH  - *Connexin 43/metabolism
MH  - Fluorocarbons
MH  - Humans
MH  - *Oxidative Stress
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Reactive Oxygen Species/metabolism
OTO - NOTNLM
OT  - Apoptosis
OT  - Connexin 43
OT  - Nephrotoxicity
OT  - Oxidative stress
OT  - Perfluorooctane sulfonate
EDAT- 2022/08/08 06:00
MHDA- 2022/09/09 06:00
CRDT- 2022/08/07 19:35
PHST- 2022/04/14 00:00 [received]
PHST- 2022/08/02 00:00 [revised]
PHST- 2022/08/03 00:00 [accepted]
PHST- 2022/08/08 06:00 [pubmed]
PHST- 2022/09/09 06:00 [medline]
PHST- 2022/08/07 19:35 [entrez]
AID - S0300-483X(22)00195-0 [pii]
AID - 10.1016/j.tox.2022.153283 [doi]
PST - ppublish
SO  - Toxicology. 2022 Aug;478:153283. doi: 10.1016/j.tox.2022.153283. Epub 2022 Aug 5.