PMID- 33600861
OWN - NLM
STAT- MEDLINE
DCOM- 20210413
LR  - 20210413
IS  - 1879-0631 (Electronic)
IS  - 0024-3205 (Linking)
VI  - 272
DP  - 2021 May 1
TI  - Nifuroxazide suppresses UUO-induced renal fibrosis in rats via inhibiting 
      STAT-3/NF-kappaB signaling, oxidative stress and inflammation.
PG  - 119241
LID - S0024-3205(21)00226-5 [pii]
LID - 10.1016/j.lfs.2021.119241 [doi]
AB  - The current work explored the influences of nifuroxazide, an in vivo inhibitor of 
      signal transducer and activator of transcription-3 (STAT-3) activation, on 
      tubulointerstitial fibrosis in rats with obstructive nephropathy using unilateral 
      ureteral obstruction (UUO) model. Thirty-two male Sprague Dawley rats were 
      assigned into 4 groups (n = 8/group) at random. Sham and UUO groups were orally 
      administered 0.5% carboxymethyl cellulose (CMC) (2.5 mL/kg/day), while Sham-NIF 
      and UUO-NIF groups were treated with 20 mg/kg/day of NIF (suspended in 0.5% CMC, 
      orally). NIF or vehicle treatments were started 2 weeks after surgery and 
      continued for further 2 weeks. NIF treatment ameliorated kidney function in UUO 
      rats, where it restored serum creatinine, blood urea, serum uric acid and urinary 
      protein and albumin to near-normal levels. NIF also markedly reduced 
      histopathological changes in tubules and glomeruli and attenuated interstitial 
      fibrosis in UUO-ligated kidneys. Mechanistically, NIF markedly attenuated renal 
      immunoexpression of E-cadherin and alpha-smooth muscle actin (alpha-SMA), diminished 
      renal oxidative stress ( downward arrow malondialdehyde (MDA) levels and  upward arrow superoxide dismutase 
      (SOD) activity), lessened renal protein expression of phosphorylated-STAT3 
      (p-STAT-3), phosphorylated-Src (p-Src) kinase, the Abelson tyrosine kinase 
      (c-Abl) and phosphorylated nuclear factor-kappaB p65 (pNF-kappaB p65), decreased 
      renal cytokine levels of transforming growth factor-beta1 (TGF-beta1), tumor necrosis 
      factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta) and monocyte chemoattractant protein-1 
      (MCP-1) and reduced number of cluster of differentiation 68 (CD68) immunolabeled 
      macrophages in UUO renal tissues, compared to levels in untreated UUO kidneys. 
      Taken together, NIF treatment suppressed interstitial fibrosis in UUO renal 
      tissues, probably via inhibiting STAT-3/NF-kappaB signaling and attenuating renal 
      oxidative stress and inflammation.
CI  - Copyright (c) 2021 Elsevier Inc. 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 - Said, Eman
AU  - Said E
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. 
      Electronic address: georgeshehatou@gmail.com.
LA  - eng
PT  - Journal Article
DEP - 20210216
PL  - Netherlands
TA  - Life Sci
JT  - Life sciences
JID - 0375521
RN  - 0 (Hydroxybenzoates)
RN  - 0 (NF-kappa B)
RN  - 0 (Nitrofurans)
RN  - 0 (STAT3 Transcription Factor)
RN  - 268B43MJ25 (Uric Acid)
RN  - PM5LI0P38J (nifuroxazide)
SB  - IM
MH  - Animals
MH  - Fibrosis/drug therapy/*metabolism
MH  - Hydroxybenzoates/metabolism/*pharmacology
MH  - Inflammation
MH  - Kidney/pathology
MH  - Kidney Diseases/pathology
MH  - Male
MH  - NF-kappa B/metabolism
MH  - Nitrofurans/metabolism/*pharmacology
MH  - Oxidative Stress/drug effects
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - STAT3 Transcription Factor/metabolism
MH  - Signal Transduction/drug effects
MH  - Ureteral Obstruction/pathology
MH  - Uric Acid/metabolism
OTO - NOTNLM
OT  - CD68
OT  - Nifuroxazide
OT  - STAT-3
OT  - TGF-beta1
OT  - TNF-alpha
OT  - Tubulointerstitial fibrosis
OT  - UUO
OT  - pNF-kappaB p65
OT  - alpha-SMA
EDAT- 2021/02/19 06:00
MHDA- 2021/04/14 06:00
CRDT- 2021/02/18 20:12
PHST- 2020/12/15 00:00 [received]
PHST- 2021/02/01 00:00 [revised]
PHST- 2021/02/09 00:00 [accepted]
PHST- 2021/02/19 06:00 [pubmed]
PHST- 2021/04/14 06:00 [medline]
PHST- 2021/02/18 20:12 [entrez]
AID - S0024-3205(21)00226-5 [pii]
AID - 10.1016/j.lfs.2021.119241 [doi]
PST - ppublish
SO  - Life Sci. 2021 May 1;272:119241. doi: 10.1016/j.lfs.2021.119241. Epub 2021 Feb 
      16.