The Iron Chelator and Anticancer Agent Dp44mT Relieves Allergic Inflammation in Mice With Allergic Rhinitis

Hee-Yun Kim1, Na-Ra Han1, Hyung-Min Kim2

  • 1Department of Pharmacology, College of Korean Medicine, Kyung Hee University, Seoul, 130-701, Republic of Korea.

Inflammation
|July 4, 2018
PubMed

Insights

The anti-cancer drug Di-2-pyridylketone-4,4-dimethyl-3-thiosemicarbazone (Dp44mT) effectively reduced allergic rhinitis symptoms in mice. Dp44mT demonstrated significant anti-inflammatory effects by lowering key inflammatory markers and cell infiltration.

Area of Science:

  • Immunology
  • Pharmacology
  • Allergy Research

Background:

  • Previous research indicated the anti-inflammatory properties of Di-2-pyridylketone-4,4-dimethyl-3-thiosemicarbazone (Dp44mT) in human mast cells.
  • The in vivo anti-inflammatory efficacy of Dp44mT, particularly in allergic rhinitis models, remained largely uninvestigated.

Purpose of the Study:

  • To evaluate the therapeutic potential of Dp44mT in mitigating the clinical manifestations of ovalbumin (OVA)-induced allergic rhinitis (AR) in a murine model.
  • To elucidate the underlying mechanisms by which Dp44mT exerts its anti-inflammatory effects in the context of AR.

Main Methods:

  • Ovalbumin (OVA)-induced allergic rhinitis (AR) was established in mice.
  • Mice were treated with Di-2-pyridylketone-4,4-dimethyl-3-thiosemicarbazone (Dp44mT).
  • Clinical symptoms, serum cytokine/chemokine levels, immunoglobulin E (IgE), histamine, and inflammatory cell infiltration in intranasal tissues were assessed.

Main Results:

  • Dp44mT administration significantly decreased clinical signs of AR, including reduced rubbing behavior.
  • Serum levels of histamine, IgE, IL-1β, TSLP, and TNF-α were significantly suppressed by Dp44mT.
  • Dp44mT modulated T helper cell responses by increasing interferon-γ (Th1) and decreasing IL-4, IL-5, and IL-13 (Th2) cytokines, while also reducing intranasal inflammatory mediators and cell infiltration.

Conclusions:

  • Di-2-pyridylketone-4,4-dimethyl-3-thiosemicarbazone (Dp44mT) demonstrates significant in vivo anti-inflammatory effects against allergic rhinitis in a mouse model.
  • Dp44mT alleviates AR symptoms by suppressing key inflammatory cytokines, chemokines, and cellular infiltration.
  • These findings suggest Dp44mT holds potential as a therapeutic agent for allergic rhinitis and related inflammatory conditions.

Related Concept Videos

Allergic Reactions02:06

Allergic Reactions

Overview
32.4K
Allergic Drug Reactions01:27

Allergic Drug Reactions

Allergic reactions related to drugs are hypersensitivity responses driven by the immune system and bear no connection to the drug's therapeutic action. While drugs in isolation do not trigger an immune response, they can interact with endogenous proteins to form antigens. These antigens stimulate lymphocytes to produce antibodies. IgE-type antibodies attach themselves to mast cells. Upon subsequent exposure to the same stimulus, the antigen-antibody interaction is initiated, unleashing...
1.5K
Inflammation01:38

Inflammation

Overview
62.2K
Complexation Equilibria: The Chelate Effect01:19

Complexation Equilibria: The Chelate Effect

In complexation reactions, metal atoms or cations interact with ligands to form donor-acceptor adducts called metal complexes. Ligands that bind through one donor site are monodentate, ligands with two donor sites are bidentate, and those with more than two donor sites are polydentate ligands. For example, ethylene diamine is a bidentate ligand that binds through two nitrogen donor atoms, forming a five-membered ring. EDTA is a polydentate ligand that binds through four oxygen and two nitrogen...
1.3K
Subviral Agents01:29

Subviral Agents

Subviral agents are infectious entities that resemble viruses but lack one or more viral components, such as a capsid or essential replication machinery. These agents include viroids, prions, and satellites, each possessing distinct structural and functional characteristics that influence their mode of infection and replication.Viroids are the simplest subviral agents, consisting of circular, single-stranded RNA molecules without a protein coat. They exclusively infect plants, relying entirely...
580
Air-entraining Agents01:27

Air-entraining Agents

Air-entraining agents improve the durability and workability of concrete in climates with frequent freezing and thawing. These agents prevent cracks by introducing small air bubbles into the mix, creating spaces accommodating water expansion when temperatures drop. The air-entraining agents lower the surface tension of water, forming stable, small air bubbles. This method is more effective than having accidental large voids, as the intentional, smaller, and evenly distributed air voids improve...
276