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Tailored small molecule for inflammation treatment: Dual scavenger targeting nitric oxide and reactive oxygen species.
- Source :
-
Journal of controlled release : official journal of the Controlled Release Society [J Control Release] 2024 Oct; Vol. 374, pp. 525-537. Date of Electronic Publication: 2024 Aug 29. - Publication Year :
- 2024
-
Abstract
- Inflammation-related diseases are often marked by elevated levels of nitric oxide (NO) and reactive oxygen species (ROS), which play important roles in the modulation of inflammation. However, the development of organic materials effective in managing NO/ROS levels has remained a challenge. This study introduces a novel organic compound, NmeGA, engineered to scavenge both NO and ROS. NmeGA ingeniously integrates N-methyl-1,2,-phenylenediamine (Nme), a NO scavenger, with gallic acid (GA), a ROS scavenger, through an amide bond, endowing it with enhanced scavenging capabilities over its individual component. This compound exhibits reduced toxicity and increased lipophilicity value, underlining its increased biological applicability and highlighting its potential as an inflammation management tool. Through in vitro studies on lipopolysaccharide (LPS)-stimulated RAW 264.7 cells, NmeGA displayed remarkable scavenging efficiency for NO and ROS, coupled with significant anti-inflammatory effects. In an LPS-induced peritonitis model, administration of NmeGA substantially decreased mortality rates, NO and ROS levels, and inflammatory cytokine concentrations. These findings highlight NmeGA's versatility as a therapeutic agent against various inflammatory diseases.<br />Competing Interests: Declaration of competing interest The authors declare no conflict of interest.<br /> (Copyright © 2024 Elsevier B.V. All rights reserved.)
- Subjects :
- Animals
Mice
RAW 264.7 Cells
Phenylenediamines pharmacology
Phenylenediamines chemistry
Gallic Acid pharmacology
Gallic Acid chemistry
Gallic Acid therapeutic use
Peritonitis drug therapy
Peritonitis chemically induced
Male
Cytokines metabolism
Reactive Oxygen Species metabolism
Nitric Oxide metabolism
Lipopolysaccharides
Anti-Inflammatory Agents pharmacology
Anti-Inflammatory Agents administration & dosage
Anti-Inflammatory Agents therapeutic use
Anti-Inflammatory Agents chemistry
Inflammation drug therapy
Inflammation metabolism
Free Radical Scavengers pharmacology
Free Radical Scavengers administration & dosage
Free Radical Scavengers therapeutic use
Subjects
Details
- Language :
- English
- ISSN :
- 1873-4995
- Volume :
- 374
- Database :
- MEDLINE
- Journal :
- Journal of controlled release : official journal of the Controlled Release Society
- Publication Type :
- Academic Journal
- Accession number :
- 39173954
- Full Text :
- https://doi.org/10.1016/j.jconrel.2024.08.026