PMID- 32950575
OWN - NLM
STAT- MEDLINE
DCOM- 20201127
LR  - 20201127
IS  - 1879-0631 (Electronic)
IS  - 0024-3205 (Linking)
VI  - 260
DP  - 2020 Nov 1
TI  - Pirfenidone attenuates gentamicin-induced acute kidney injury by inhibiting 
      inflammasome-dependent NLRP3 pathway in rats.
PG  - 118454
LID - S0024-3205(20)31207-8 [pii]
LID - 10.1016/j.lfs.2020.118454 [doi]
AB  - Acute kidney injury (AKI) is an abrupt and usually reversible decline in renal 
      function. AKI is considered one of the main drawbacks of the use of gentamicin 
      that critically limits its clinical use. In this study, pirfenidone, an oral 
      antifibrotic drug, was given to rats (200 mg/kg, p.o., daily) for seven days 
      alone before the initiation of gentamicin treatment and continued for seven days 
      alongside daily gentamicin injections. In gentamicin group, gentamicin was given 
      to Wistar rats (100 mg/kg, i.p., daily) for seven days to induce AKI. Pirfenidone 
      managed to alleviate gentamicin-induced AKI by improving kidney function 
      parameters including serum creatinine, blood urea nitrogen (BUN), proteinuria, 
      relative kidney-to-body weight ratio and creatinine clearance. Pirfenidone 
      decreased cytotoxicity induced by gentamicin by decreasing lactate dehydrogenase 
      (LDH) activity and improving histologic picture of tubules and glomeruli. 
      Pirfenidone also alleviated oxidative stress induced by gentamicin by reducing 
      malondialdehyde (MDA) and elevating reduced glutathione (GSH). Pirfenidone 
      prevented the upregulated inflammasome pathway markers in the kidney. It 
      succeeded in decreasing toll like recpetor-4 (TLR4), nuclear factor-kappa B 
      (NF-kappaB), nucleotide-binding oligomerization domain [NOD]-like pyrin domain 
      containing protein 3 (NLRP3), caspase-1, interleukin-1beta (IL-1beta) and IL-18 levels. 
      Additionally, Pirfenidone caused a decrease in macrophage infiltration displayed 
      by reduction in renal monocyte chemoattractant protein-1 (MCP-1) levels. To sum 
      up, pirfenidone can effectively mitigate gentamicin-induced AKI by inhibiting 
      oxidative stress, macrophage infiltration and inflammasome-dependent NLRP3 
      pathway-induced inflammation.
CI  - Copyright (c) 2020 Elsevier Inc. All rights reserved.
FAU - Sharawy, Maha H
AU  - Sharawy MH
AD  - Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura 
      University, Mansoura 35516, Egypt. Electronic address: maha_hesham@mans.edu.eg.
FAU - Serrya, Marwa S
AU  - Serrya MS
AD  - Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura 
      University, Mansoura 35516, Egypt.
LA  - eng
PT  - Journal Article
DEP - 20200918
PL  - Netherlands
TA  - Life Sci
JT  - Life sciences
JID - 0375521
RN  - 0 (Ccl2 protein, rat)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Gentamicins)
RN  - 0 (Inflammasomes)
RN  - 0 (NLR Family, Pyrin Domain-Containing 3 Protein)
RN  - 0 (Nlrp3 protein, rat)
RN  - 0 (Protective Agents)
RN  - 0 (Pyridones)
RN  - 0 (Tlr4 protein, rat)
RN  - 0 (Toll-Like Receptor 4)
RN  - D7NLD2JX7U (pirfenidone)
RN  - EC 1.1.1.27 (L-Lactate Dehydrogenase)
SB  - IM
MH  - Acute Kidney Injury/*chemically induced/*drug therapy/metabolism/pathology
MH  - Animals
MH  - Body Weight
MH  - Chemokine CCL2/metabolism
MH  - Gentamicins/*adverse effects
MH  - Inflammasomes/*drug effects/metabolism
MH  - Kidney Function Tests
MH  - L-Lactate Dehydrogenase/blood
MH  - Male
MH  - NLR Family, Pyrin Domain-Containing 3 Protein/*metabolism
MH  - Oxidative Stress/drug effects
MH  - Protective Agents
MH  - Pyridones/*pharmacology
MH  - Rats, Wistar
MH  - Toll-Like Receptor 4/metabolism
OTO - NOTNLM
OT  - Acute kidney injury (AKI)
OT  - Caspase-1
OT  - Interleukin-1beta
OT  - NLRP3 inflammasome
OT  - Pirfenidone
OT  - Toll like receptor-4 (TLR-4)
EDAT- 2020/09/21 06:00
MHDA- 2020/11/28 06:00
CRDT- 2020/09/20 20:27
PHST- 2020/08/01 00:00 [received]
PHST- 2020/09/08 00:00 [revised]
PHST- 2020/09/13 00:00 [accepted]
PHST- 2020/09/21 06:00 [pubmed]
PHST- 2020/11/28 06:00 [medline]
PHST- 2020/09/20 20:27 [entrez]
AID - S0024-3205(20)31207-8 [pii]
AID - 10.1016/j.lfs.2020.118454 [doi]
PST - ppublish
SO  - Life Sci. 2020 Nov 1;260:118454. doi: 10.1016/j.lfs.2020.118454. Epub 2020 Sep 
      18.