PMID- 33617955
OWN - NLM
STAT- MEDLINE
DCOM- 20210519
LR  - 20240226
IS  - 1872-7077 (Electronic)
IS  - 1382-6689 (Linking)
VI  - 84
DP  - 2021 May
TI  - Dasatinib mitigates renal fibrosis in a rat model of UUO via inhibition of 
      Src/STAT-3/NF-kappaB signaling.
PG  - 103625
LID - S1382-6689(21)00043-0 [pii]
LID - 10.1016/j.etap.2021.103625 [doi]
AB  - This research aimed to investigate the reno-protective impact of the tyrosine 
      kinase inhibitor dasatinib (DAS) against renal fibrosis induced by unilateral 
      ureteral obstruction (UUO) in rats. DAS administration improved renal function 
      and mitigated renal oxidative stress with paralleled reduction in the ligated 
      kidney mass index, significant retraction in renal histopathological alterations 
      and suppression of renal interstitial fibrosis. Nevertheless, DAS administration 
      attenuated renal expression of phosphorylated Src (p-Src), Abelson (c-Abl) 
      tyrosine kinases, nuclear factor-kappaB (NF-kappaB) p65, and phosphorylated signal 
      transducer and activator of transcription-3 (p-STAT-3)/STAT-3 with paralleled 
      reduction in renal contents of tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta 
      (IL-1beta), and monocyte chemoattractant protein-1 (MCP-1). DAS diminished 
      interstitial macrophage infiltration and decreased renal profibrotic transforming 
      growth factor-beta1 (TGF-beta1) levels and suppressed interstitial expression of renal 
      alpha-smooth muscle actin (alpha-SMA) and fibronectin. Collectively, DAS slowed the 
      progression of renal interstitial fibrosis, possibly via attenuating renal 
      oxidative stress, impairing Src/STAT-3/NF-kappaB signaling, and reducing renal 
      inflammation.
CI  - Copyright (c) 2021 Elsevier B.V. All rights reserved.
FAU - Hassan, Nabila M E
AU  - Hassan NME
AD  - Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura 
      University, Mansoura, Egypt.
FAU - Shehatou, George S G
AU  - Shehatou GSG
AD  - Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura 
      University, Mansoura, Egypt; Department of Pharmacology and Biochemistry, Faculty 
      of Pharmacy, Delta University for Science and Technology, Gamasa City, Egypt.
FAU - Kenawy, Hany Ibrahim
AU  - Kenawy HI
AD  - Department of Microbiology and Immunology, Faculty of Pharmacy, Mansoura 
      University, Mansoura, Egypt.
FAU - Said, Eman
AU  - Said E
AD  - Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura 
      University, Mansoura, Egypt. Electronic address: emansaid@mans.edu.eg.
LA  - eng
PT  - Journal Article
DEP - 20210219
PL  - Netherlands
TA  - Environ Toxicol Pharmacol
JT  - Environmental toxicology and pharmacology
JID - 9612020
RN  - 0 (Cytokines)
RN  - 0 (NF-kappa B)
RN  - 0 (Protective Agents)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 0 (STAT3 Transcription Factor)
RN  - 0 (Stat3 protein, rat)
RN  - EC 2.7.10.2 (Proto-Oncogene Proteins c-abl)
RN  - EC 2.7.10.2 (src-Family Kinases)
RN  - RBZ1571X5H (Dasatinib)
SB  - IM
MH  - Animals
MH  - Cytokines/immunology
MH  - Dasatinib/pharmacology/*therapeutic use
MH  - Disease Models, Animal
MH  - Fibrosis
MH  - Kidney/drug effects/immunology/metabolism/pathology
MH  - Macrophages/drug effects/immunology
MH  - Male
MH  - NF-kappa B/metabolism
MH  - Oxidative Stress/drug effects
MH  - Protective Agents/pharmacology/*therapeutic use
MH  - Protein Kinase Inhibitors/pharmacology/*therapeutic use
MH  - Proto-Oncogene Proteins c-abl/metabolism
MH  - Rats, Sprague-Dawley
MH  - STAT3 Transcription Factor/metabolism
MH  - Signal Transduction/drug effects
MH  - Ureteral Obstruction/*drug therapy/immunology/metabolism/pathology
MH  - src-Family Kinases/metabolism
MH  - Rats
OTO - NOTNLM
OT  - CD68
OT  - Dasatinib
OT  - STAT-3
OT  - Unilateral ureteral obstruction (UUO)
OT  - p-Src
OT  - alpha-SMA
EDAT- 2021/02/23 06:00
MHDA- 2021/05/20 06:00
CRDT- 2021/02/22 20:10
PHST- 2020/10/03 00:00 [received]
PHST- 2021/02/14 00:00 [revised]
PHST- 2021/02/17 00:00 [accepted]
PHST- 2021/02/23 06:00 [pubmed]
PHST- 2021/05/20 06:00 [medline]
PHST- 2021/02/22 20:10 [entrez]
AID - S1382-6689(21)00043-0 [pii]
AID - 10.1016/j.etap.2021.103625 [doi]
PST - ppublish
SO  - Environ Toxicol Pharmacol. 2021 May;84:103625. doi: 10.1016/j.etap.2021.103625. 
      Epub 2021 Feb 19.