PMID- 37234710
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230528
IS  - 1663-9812 (Print)
IS  - 1663-9812 (Electronic)
IS  - 1663-9812 (Linking)
VI  - 14
DP  - 2023
TI  - Dietary administration of the glycolytic inhibitor 2-deoxy-D-glucose reduces 
      endotoxemia-induced inflammation and oxidative stress: Implications in 
      PAMP-associated acute and chronic pathology.
PG  - 940129
LID - 10.3389/fphar.2023.940129 [doi]
LID - 940129
AB  - Pathogen-associated molecular patterns (PAMPs) like bacterial cell wall 
      components and viral nucleic acids are known ligands of innate inflammatory 
      receptors that trigger multiple inflammatory pathways that may result in acute 
      inflammation and oxidative stress-driven tissue and organ toxicity. When 
      dysregulated, this inflammation may lead to acute toxicity and multiorgan 
      failure. Inflammatory events are often driven by high energy demands and 
      macromolecular biosynthesis. Therefore, we proposed that targeting the metabolism 
      of lipopolysaccharide (LPS)-driven inflammatory events, using an energy 
      restriction approach, can be an effective strategy to prevent the acute or 
      chronic detrimental effects of accidental or seasonal bacterial and other 
      pathogenic exposures. In the present study, we investigated the potential of 
      energy restriction mimetic agent (ERMA) 2-deoxy-D-glucose (2-DG) in targeting the 
      metabolism of inflammatory events during LPS-elicited acute inflammatory 
      response. Mice fed with 2-DG as a dietary component in drinking water showed 
      reduced LPS-driven inflammatory processes. Dietary 2-DG reduced LPS-induced lung 
      endothelial damage and oxidative stress by strengthening the antioxidant defense 
      system and limiting the activation and expression of inflammatory proteins, viz., 
      P-Stat-3, NfkappaBeta, and MAP kinases. This was accompanied by decreased TNF, IL-1beta, 
      and IL-6 levels in peripheral blood and bronchoalveolar lavage fluid (BALF). 2-DG 
      also reduced the infiltration of PMNCs (polymorphonuclear cells) in inflamed 
      tissues. Altered glycolysis and improved mitochondrial activity in 2-DG-treated 
      RAW 264.7 macrophage cells suggested possible impairment of macrophage metabolism 
      and, therefore, activation in macrophages. Taken together, the present study 
      suggests that inclusion of glycolytic inhibitor 2-DG as a part of the diet can be 
      helpful in preventing the severity and poor prognosis associated with 
      inflammatory events during bacterial and other pathogenic exposures.
CI  - Copyright (c) 2023 Pandey, Anang, Singh, Seth, Bhatt, Kalra, Manda, Soni, Roy, 
      Natarajan and Dwarakanath.
FAU - Pandey, Sanjay
AU  - Pandey S
AD  - Division of Radiation Biosciences, Institute of Nuclear Medicine and Allied 
      Sciences, Delhi, India.
AD  - Infectious Disease Immunology Laboratory, Dr. B.R. Ambedkar Center for Biomedical 
      Research, University of Delhi, Delhi, India.
AD  - Department of Radiation Oncology, Albert Einstein College of Medicine, Bronx, NY, 
      United States.
FAU - Anang, Vandana
AU  - Anang V
AD  - Infectious Disease Immunology Laboratory, Dr. B.R. Ambedkar Center for Biomedical 
      Research, University of Delhi, Delhi, India.
FAU - Singh, Saurabh
AU  - Singh S
AD  - Division of Radiation Biosciences, Institute of Nuclear Medicine and Allied 
      Sciences, Delhi, India.
AD  - Infectious Disease Immunology Laboratory, Dr. B.R. Ambedkar Center for Biomedical 
      Research, University of Delhi, Delhi, India.
AD  - Department of Radiation Oncology, Albert Einstein College of Medicine, Bronx, NY, 
      United States.
FAU - Seth, Saurabh
AU  - Seth S
AD  - Division of Radiation Biosciences, Institute of Nuclear Medicine and Allied 
      Sciences, Delhi, India.
FAU - Bhatt, Anant Narayan
AU  - Bhatt AN
AD  - Division of Radiation Biosciences, Institute of Nuclear Medicine and Allied 
      Sciences, Delhi, India.
FAU - Kalra, Namita
AU  - Kalra N
AD  - Division of Radiation Biosciences, Institute of Nuclear Medicine and Allied 
      Sciences, Delhi, India.
FAU - Manda, Kailash
AU  - Manda K
AD  - Division of Radiation Biosciences, Institute of Nuclear Medicine and Allied 
      Sciences, Delhi, India.
FAU - Soni, Ravi
AU  - Soni R
AD  - Division of Radiation Biosciences, Institute of Nuclear Medicine and Allied 
      Sciences, Delhi, India.
FAU - Roy, Bal Gangadhar
AU  - Roy BG
AD  - Division of Radiation Biosciences, Institute of Nuclear Medicine and Allied 
      Sciences, Delhi, India.
FAU - Natarajan, K
AU  - Natarajan K
AD  - Infectious Disease Immunology Laboratory, Dr. B.R. Ambedkar Center for Biomedical 
      Research, University of Delhi, Delhi, India.
FAU - Dwarakanath, Bilikere S
AU  - Dwarakanath BS
AD  - Division of Radiation Biosciences, Institute of Nuclear Medicine and Allied 
      Sciences, Delhi, India.
LA  - eng
PT  - Journal Article
DEP - 20230510
PL  - Switzerland
TA  - Front Pharmacol
JT  - Frontiers in pharmacology
JID - 101548923
PMC - PMC10206263
OTO - NOTNLM
OT  - chronic inflammation
OT  - energy restriction
OT  - glycolysis
OT  - metabolism
OT  - neutrophils
OT  - pathogens
OT  - polymorphonuclear cells
OT  - sepsis
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2023/05/26 19:15
MHDA- 2023/05/26 19:16
PMCR- 2023/05/10
CRDT- 2023/05/26 12:15
PHST- 2022/05/10 00:00 [received]
PHST- 2023/04/20 00:00 [accepted]
PHST- 2023/05/26 19:16 [medline]
PHST- 2023/05/26 19:15 [pubmed]
PHST- 2023/05/26 12:15 [entrez]
PHST- 2023/05/10 00:00 [pmc-release]
AID - 940129 [pii]
AID - 10.3389/fphar.2023.940129 [doi]
PST - epublish
SO  - Front Pharmacol. 2023 May 10;14:940129. doi: 10.3389/fphar.2023.940129. 
      eCollection 2023.