PMID- 33689686
OWN - NLM
STAT- MEDLINE
DCOM- 20210407
LR  - 20210407
IS  - 1879-0631 (Electronic)
IS  - 0024-3205 (Linking)
VI  - 273
DP  - 2021 May 15
TI  - A novel gastroprotective effect of zeaxanthin against stress-induced gastritis in 
      male rats targeting the expression of HIF-1alpha, TFF-1 and MMP-9 through 
      PI3K/Akt/JNK signaling pathway.
PG  - 119297
LID - S0024-3205(21)00282-4 [pii]
LID - 10.1016/j.lfs.2021.119297 [doi]
AB  - Stress-induced gastritis is a common problem in the intensive care unit. 
      Zeaxanthin (ZE), a non-provitamin A carotenoid has been known to exert 
      antioxidant and anti-inflammatory effects. In this study, we examined the effect 
      of ZE on water avoidance stress (WAS)-induced gastritis in rats. 24 Sprague' 
      Dawley male rats were divided into four groups; control, ZE, WAS and WAS+ZE. In 
      the stressed rats, treatment with ZE effectively downregulated the gastric levels 
      of total oxidant status (TOS), myeloperoxidase (MPO) and malondialdehyde (MDA), 
      with significant upregulation of the antioxidant enzymes' activities and gastric 
      levels of prostagladin-E2 (PGE2) as compared to the untreated stressed one. As 
      noticed in the present study, ZE significantly decrease the gastric levels of 
      interleukin-1 beta (IL-1beta) and IL-6 as well as suppression of nuclear transcription 
      factor kappa-B (NF-kappaB) immunohistochemical expression together with upregulation 
      of trefoil factor-1 (TFF-1) gene expression. Moreover, in the untreated 
      WAS-induced gastritis group, gastrin and corticosterone levels were significantly 
      increased together with upregulation of the gene expression of hypoxia inducible 
      factor-1alpha (HIF-1alpha), matrix metalloproteinase-9 (MMP-9), PI3K, Akt and JNK in the 
      gastric tissues, which significantly improved by ZE administration. These all 
      positive effects of ZE reflected on reduction of microscopic gastric mucosal 
      damage and inflammatory cell infiltration with improvement of ulcer score. Our 
      results discover that ZE has a new gastroprotective effect against stress-induced 
      gastritis in rats, primarily through its antioxidative and anti-inflammatory 
      effects, which are expressed in the regulation of the MMP-9 and HIF-1alpha signaling 
      pathways.
CI  - Copyright (c) 2021. Published by Elsevier Inc.
FAU - Elhadidy, Mona G
AU  - Elhadidy MG
AD  - Department of Medical Physiology, Faculty of Medicine, Mansoura University, 
      Egypt; Department of Medical Physiology, Faculty of Medicine, Al-Baha University, 
      Saudi Arabia. Electronic address: mona.gaber2012@yahoo.com.
FAU - El Nashar, Eman Mohamad
AU  - El Nashar EM
AD  - Department of Anatomy, College of Medicine, King Khalid University, Abha 61421, 
      Saudi Arabia; Department of Histology and Cell Biology of Medicine, Benha 
      University, Egypt. Electronic address: enshar@kku.edu.sa.
FAU - Alghamdi, Mansour A
AU  - Alghamdi MA
AD  - Department of Anatomy, College of Medicine, King Khalid University, Abha 61421, 
      Saudi Arabia; Genomics and Personalized Medicine Unit, College of Medicine, King 
      Khalid University, Abha 61421, Saudi Arabia. Electronic address: 
      m.alghamdi@kku.edu.sa.
FAU - Samir, Shereen M
AU  - Samir SM
AD  - Department of Medical Physiology, Faculty of Medicine, Mansoura University, 
      Egypt. Electronic address: shereensamir2017@hotmail.com.
LA  - eng
PT  - Journal Article
DEP - 20210306
PL  - Netherlands
TA  - Life Sci
JT  - Life sciences
JID - 0375521
RN  - 0 (Antioxidants)
RN  - 0 (Biomarkers)
RN  - 0 (Cytokines)
RN  - 0 (Hif1a protein, rat)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (Protective Agents)
RN  - 0 (Tff1 protein, rat)
RN  - 0 (Trefoil Factor-1)
RN  - 0 (Zeaxanthins)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.12.2 (MAP Kinase Kinase 4)
RN  - EC 3.4.24.35 (Matrix Metalloproteinase 9)
RN  - EC 3.4.24.35 (Mmp9 protein, rat)
SB  - IM
MH  - Animals
MH  - Antioxidants/metabolism
MH  - Biomarkers/*analysis
MH  - Cytokines/metabolism
MH  - Gastritis/*drug therapy/etiology/metabolism/pathology
MH  - Gene Expression Regulation/*drug effects
MH  - Hypoxia-Inducible Factor 1, alpha Subunit/genetics/metabolism
MH  - MAP Kinase Kinase 4/genetics/metabolism
MH  - Male
MH  - Matrix Metalloproteinase 9/genetics/metabolism
MH  - Oxidative Stress
MH  - Phosphatidylinositol 3-Kinases/genetics/metabolism
MH  - Protective Agents/*pharmacology
MH  - Proto-Oncogene Proteins c-akt/genetics/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - *Stress, Physiological
MH  - Trefoil Factor-1/genetics/metabolism
MH  - Zeaxanthins/*pharmacology
OTO - NOTNLM
OT  - Akt
OT  - HIF-1alpha
OT  - JNK
OT  - MMP-9
OT  - NF-kappaB
OT  - PI3K
OT  - TFF-1
OT  - WAS
EDAT- 2021/03/11 06:00
MHDA- 2021/04/10 06:00
CRDT- 2021/03/10 17:40
PHST- 2021/01/13 00:00 [received]
PHST- 2021/02/21 00:00 [revised]
PHST- 2021/02/26 00:00 [accepted]
PHST- 2021/03/11 06:00 [pubmed]
PHST- 2021/04/10 06:00 [medline]
PHST- 2021/03/10 17:40 [entrez]
AID - S0024-3205(21)00282-4 [pii]
AID - 10.1016/j.lfs.2021.119297 [doi]
PST - ppublish
SO  - Life Sci. 2021 May 15;273:119297. doi: 10.1016/j.lfs.2021.119297. Epub 2021 Mar 
      6.