PMID- 30087305
OWN - NLM
STAT- MEDLINE
DCOM- 20181108
LR  - 20190710
IS  - 1420-3049 (Electronic)
IS  - 1420-3049 (Linking)
VI  - 23
IP  - 8
DP  - 2018 Aug 7
TI  - Protective Effects of Nintedanib against Polyhexamethylene Guanidine 
      Phosphate-Induced Lung Fibrosis in Mice.
LID - 10.3390/molecules23081974 [doi]
LID - 1974
AB  - Nintedanib (NDN), a tyrosine kinase inhibitor, has been shown to have anti-tumor, 
      anti-inflammatory, and anti-fibrotic effects in several reports. We investigated 
      the protective effects of NDN against polyhexamethylene guanidine phosphate 
      (PHMG)-induced lung fibrosis in mice. The following three experimental groups 
      were evaluated: (1) vehicle control; (2) PHMG (1.1 mg/kg); and (3) PHMG & NDN (60 
      mg/kg). PHMG induced pulmonary inflammation and fibrosis by intratracheal 
      instillation in mice. In contrast, NDN treatment effectively alleviated the PHMG 
      induced lung injury, and attenuated the number of total cells and inflammatory 
      cells in the bronchoalveolar lavage fluid, including the fibrotic 
      histopathological changes, and also reduced the hydroxyproline content. NDN also 
      significantly decreased the expression of inflammatory cytokines and fibrotic 
      factors, and the activation of the NLRP3 inflammasome in lung tissues. These 
      results suggest that NDN may mitigate the inflammatory response and development 
      of pulmonary fibrosis in the lungs of mice treated with PHMG.
FAU - Kim, Hyeon-Young
AU  - Kim HY
AD  - National Center for Efficacy Evaluation of Respiratory Disease Product, Korea 
      Institute of Toxicology, 30, Baekhak 1-gil, Jeongeup-si 56212, Korea. 
      hyeonyoung.kim@kitox.re.kr.
AD  - Department of Toxicology Evaluation, Graduate School of Pre-Clinical Laboratory 
      Science, Konyang University, Daejeon 35365, Korea. hyeonyoung.kim@kitox.re.kr.
FAU - Kim, Min-Seok
AU  - Kim MS
AD  - National Center for Efficacy Evaluation of Respiratory Disease Product, Korea 
      Institute of Toxicology, 30, Baekhak 1-gil, Jeongeup-si 56212, Korea. 
      minseok.kim@kitox.re.kr.
FAU - Kim, Sung-Hwan
AU  - Kim SH
AD  - National Center for Efficacy Evaluation of Respiratory Disease Product, Korea 
      Institute of Toxicology, 30, Baekhak 1-gil, Jeongeup-si 56212, Korea. 
      sunghwan.kim@kitox.re.kr.
AD  - Department of Human and Environmental Toxicology, University of Science & 
      Technology, Daejeon 34113, Korea. sunghwan.kim@kitox.re.kr.
FAU - Joen, Doin
AU  - Joen D
AD  - National Center for Efficacy Evaluation of Respiratory Disease Product, Korea 
      Institute of Toxicology, 30, Baekhak 1-gil, Jeongeup-si 56212, Korea. 
      doin.jeon@kitox.re.kr.
FAU - Lee, Kyuhong
AU  - Lee K
AD  - National Center for Efficacy Evaluation of Respiratory Disease Product, Korea 
      Institute of Toxicology, 30, Baekhak 1-gil, Jeongeup-si 56212, Korea. 
      khleekit@gmail.com.
AD  - Department of Human and Environmental Toxicology, University of Science & 
      Technology, Daejeon 34113, Korea. khleekit@gmail.com.
LA  - eng
PT  - Journal Article
DEP - 20180807
PL  - Switzerland
TA  - Molecules
JT  - Molecules (Basel, Switzerland)
JID - 100964009
RN  - 0 (Cytokines)
RN  - 0 (Guanidines)
RN  - 0 (Indoles)
RN  - 0 (Inflammasomes)
RN  - 0 (Inflammation Mediators)
RN  - 0 (NLR Family, Pyrin Domain-Containing 3 Protein)
RN  - 0 (Nlrp3 protein, mouse)
RN  - 0 (Protective Agents)
RN  - 31961-54-3 (polyhexamethyleneguanidine)
RN  - G6HRD2P839 (nintedanib)
RN  - RMB44WO89X (Hydroxyproline)
SB  - IM
MH  - Animals
MH  - Body Weight/drug effects
MH  - Bronchoalveolar Lavage Fluid/cytology
MH  - Cell Count
MH  - Cytokines/metabolism
MH  - Guanidines
MH  - Hydroxyproline/metabolism
MH  - Indoles/pharmacology/*therapeutic use
MH  - Inflammasomes/metabolism
MH  - Inflammation Mediators/metabolism
MH  - Lung/metabolism/pathology
MH  - Male
MH  - Mice, Inbred C57BL
MH  - NLR Family, Pyrin Domain-Containing 3 Protein/metabolism
MH  - Organ Size/drug effects
MH  - Protective Agents/pharmacology/*therapeutic use
MH  - Pulmonary Fibrosis/*chemically induced/*drug therapy/pathology
PMC - PMC6222351
OTO - NOTNLM
OT  - anti-fibrosis
OT  - inflammasome
OT  - nintedanib
OT  - polyhexamethylene guanidine phosphate
OT  - pulmonary fibrosis
COIS- The authors declare no conflict of interest.
EDAT- 2018/08/09 06:00
MHDA- 2018/11/09 06:00
PMCR- 2018/08/07
CRDT- 2018/08/09 06:00
PHST- 2018/06/26 00:00 [received]
PHST- 2018/07/19 00:00 [revised]
PHST- 2018/08/06 00:00 [accepted]
PHST- 2018/08/09 06:00 [entrez]
PHST- 2018/08/09 06:00 [pubmed]
PHST- 2018/11/09 06:00 [medline]
PHST- 2018/08/07 00:00 [pmc-release]
AID - molecules23081974 [pii]
AID - molecules-23-01974 [pii]
AID - 10.3390/molecules23081974 [doi]
PST - epublish
SO  - Molecules. 2018 Aug 7;23(8):1974. doi: 10.3390/molecules23081974.