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Protective effect of ARE-inducing phenol antioxidant TS-13 in chronic inflammation

E B Menshchikova1, N K Zenkov, V O Tkachev

  • 1Research Center of Clinical and Experimental Medicine, Siberian Division of the Russian Academy of Medical Sciences, Novosibirsk; Novosibirsk State Pedagogical University, Russia. lemen@soramn.ru.

Bulletin of Experimental Biology and Medicine
|October 19, 2013
PubMed

Insights

The compound TS-13 modulates oxidative metabolism in leukocytes during inflammation. While not affecting acute inflammation markers, it partially inhibits inflammatory responses in chronic conditions like rheumatoid polyarthritis.

Area of Science:

  • Biochemistry
  • Immunology
  • Pharmacology

Background:

  • Chronic inflammation involves complex immune responses and oxidative stress.
  • The Nrf2/Keap1/ARE signaling pathway plays a crucial role in cellular defense against oxidative stress.
  • Monophenol TS-13 is investigated for its potential to modulate this pathway.

Purpose of the Study:

  • To investigate the protective effects of TS-13 on chronic inflammation models.
  • To assess the impact of TS-13 on the Nrf2/Keap1/ARE signaling system in vivo.
  • To evaluate TS-13's efficacy in reducing oxidative metabolism and inflammatory markers.

Main Methods:

  • TS-13 was administered in an air pouch model of acute inflammation.
  • Rheumatoid polyarthritis was induced using heterologous collagen in vivo.
  • Exudate volume, protein content, cell count, oxidative metabolism, and H2O2 generation were measured.

Main Results:

  • TS-13 did not alter exudate volume, protein, or cell count in acute inflammation.
  • TS-13 significantly reduced oxidative metabolism intensity in leukocytes from acute inflammation exudates.
  • In chronic rheumatoid polyarthritis, TS-13 showed reduced efficacy on clinical signs but inhibited H2O2 generation by monocytes and neutrophils.

Conclusions:

  • The phlogolytic effect of the Nrf2/Keap1/ARE signaling system is less pronounced in chronic immune-mediated inflammation compared to acute inflammation.
  • TS-13 demonstrates a modulatory effect on oxidative stress in inflammatory leukocytes.
  • The efficacy of TS-13 may be stage-dependent in chronic inflammatory diseases.

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