PMID- 37295485
OWN - NLM
STAT- MEDLINE
DCOM- 20230630
LR  - 20230702
IS  - 1878-1519 (Electronic)
IS  - 1569-9048 (Linking)
VI  - 314
DP  - 2023 Aug
TI  - Fenofibrate attenuates asthma features in an ovalbumin-induced mouse model via 
      suppressing NF-kappaB binding activity.
PG  - 104083
LID - S1569-9048(23)00071-X [pii]
LID - 10.1016/j.resp.2023.104083 [doi]
AB  - BACKGROUND/AIM: Asthma is a chronic inflammatory disease of the airways with a 
      high prevalence. Asthma has a complex pathophysiology and about 5-10% of patients 
      are not fully responsive to the currently available treatments. The aim of this 
      study is to investigate the involvement of NF-kappaB in the effects of fenofibrate on 
      a mouse model of allergic asthma. MATERIALS AND METHODS: A total of 49 BALB/c 
      mice were randomly distributed into 7 groups (n = 7). Allergic asthma model was 
      created by administering i.p. injections of ovalbumin on days 0, 14 and 21, 
      followed by provocation with inhaled ovalbumin on days 28, 29 and 30. Fenofibrate 
      was orally given in 3 different doses; 1, 10 and 30 mg/kg through days 21-30 of 
      the experiment. On day 31, pulmonary function test using whole body 
      plethysmography was performed. The mice were sacrificed 24 h later. Blood samples 
      were obtained, and serum of each sample was separated for IgE determination. 
      Bronchoalveolar lavage fluid (BALF) and lung tissues were collected to measure 
      IL-5 and IL-13 levels. Nuclear extracts of lung tissues were employed to assess 
      nuclear factor kappa B (NF-kappaB) p65 binding activity. RESULTS: Enhanced Pause 
      (Penh) values were significantly increased in ovalbumin-sensitized and challenged 
      mice (p < 0.01). Administration of fenofibrate (10 and 30 mg/kg) resulted in 
      improved pulmonary function as shown by significantly lower Penh values 
      (p < 0.01). Interleukin (IL) - 5 and IL-13 levels in BALF and lung tissues and 
      immunoglobulin E (IgE) levels in serum were significantly elevated in the 
      allergic mice. IL-5 levels in the lung tissues of mice treated with 1 mg/kg 
      fenofibrate (FEN1) group were significantly reduced (p < 0.01). BALF and lung 
      tissue IL-5 and IL-13 levels in mice treated with 10 and 30 mg/kg fenofibrate, 
      FEN10 and FEN30, respectively, were significantly diminished when compared to the 
      ovalbumin-treated (OVA) group, whereas treatment with 1 mg/kg fenofibrate 
      resulted in insignificant changes. IgE levels in the serum of FEN30 group mice 
      have shown a prominent reduction (p < 0.01). NF-kappaB p65 binding activity was 
      higher in mice sensitized and challenged with ovalbumin (p < 0.01). NF-kappaB p65 
      binding activity was significantly reduced in allergic mice treated with 30 mg/kg 
      (p < 0.01) fenofibrate. CONCLUSIONS: In this study, we showed that administration 
      of 10 and 30 mg/kg fenofibrate effectively attenuated airway hyperresponsiveness 
      and inflammation in a mouse model of allergic asthma, possibly through inhibition 
      of NF-kappaB binding activity.
CI  - Copyright (c) 2023 Elsevier B.V. All rights reserved.
FAU - Alhirmizi, Ibraheem Akram Omar
AU  - Alhirmizi IAO
AD  - Directorate of Health, Kirkuk, Iraq.
FAU - Uysal, Fatma
AU  - Uysal F
AD  - Department of Pharmacology, Faculty of Medicine, Ankara Yildirim Beyazit 
      University, Ankara, Turkiye.
FAU - Arslan, Seyfullah Oktay
AU  - Arslan SO
AD  - Department of Pharmacology, Faculty of Medicine, Ankara Yildirim Beyazit 
      University, Ankara, Turkiye. Electronic address: soarslan@gmail.com.
FAU - Ozunlu, Saliha Aysenur Cam
AU  - Ozunlu SAC
AD  - Department of Pharmacology, Faculty of Medicine, Ankara Yildirim Beyazit 
      University, Ankara, Turkiye.
FAU - Koc, Aysegul
AU  - Koc A
AD  - Department of Pharmacology, Ankara Yildirim Beyazit University, Ankara, Turkiye.
FAU - Parlar, Ali
AU  - Parlar A
AD  - Department of Pharmacology, Faculty of Medicine, Adiyaman University, Adiyaman, 
      Turkiye.
FAU - Bayram, Keziban Korkmaz
AU  - Bayram KK
AD  - Department of Medical Genetics, Faculty of Medicine, Ankara Yildirim Beyazit 
      University, Ankara, Turkiye "Central Research Laboratory" Research and 
      Application Center, Ankara Yildirim Beyazit University, Ankara, Turkiye.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20230608
PL  - Netherlands
TA  - Respir Physiol Neurobiol
JT  - Respiratory physiology & neurobiology
JID - 101140022
RN  - 0 (NF-kappa B)
RN  - 9006-59-1 (Ovalbumin)
RN  - 0 (Interleukin-5)
RN  - U202363UOS (Fenofibrate)
RN  - 0 (Interleukin-13)
RN  - 0 (Anti-Inflammatory Agents)
RN  - 37341-29-0 (Immunoglobulin E)
RN  - 0 (Cytokines)
SB  - IM
MH  - Mice
MH  - Animals
MH  - NF-kappa B/metabolism
MH  - Ovalbumin/pharmacology
MH  - Interleukin-5/metabolism
MH  - *Fenofibrate/pharmacology/therapeutic use/metabolism
MH  - Interleukin-13/metabolism
MH  - Anti-Inflammatory Agents/pharmacology
MH  - Immunoglobulin E/metabolism/pharmacology
MH  - *Asthma/chemically induced/drug therapy/metabolism
MH  - Lung/metabolism
MH  - Bronchoalveolar Lavage Fluid
MH  - *Hypersensitivity/drug therapy
MH  - Mice, Inbred BALB C
MH  - Disease Models, Animal
MH  - Cytokines/metabolism
OTO - NOTNLM
OT  - Fenofibrate
OT  - NF-kappaB-binding activity
OT  - Ovalbumin-induced asthma
OT  - Whole-body Plethysmography
COIS- Declaration of Competing Interest The authors declare that there is no conflict 
      of interests.
EDAT- 2023/06/10 15:14
MHDA- 2023/06/30 06:42
CRDT- 2023/06/09 19:23
PHST- 2023/02/24 00:00 [received]
PHST- 2023/05/07 00:00 [revised]
PHST- 2023/05/20 00:00 [accepted]
PHST- 2023/06/30 06:42 [medline]
PHST- 2023/06/10 15:14 [pubmed]
PHST- 2023/06/09 19:23 [entrez]
AID - S1569-9048(23)00071-X [pii]
AID - 10.1016/j.resp.2023.104083 [doi]
PST - ppublish
SO  - Respir Physiol Neurobiol. 2023 Aug;314:104083. doi: 10.1016/j.resp.2023.104083. 
      Epub 2023 Jun 8.