Anti-inflammatory activity of the antiallergic drug 7-[4-(4-benzhydrylpiperazinyl-1)butyl]-3-methylxanthine succinate (theoritin)
- Authors: Gushchin I.S.1, Kryshen K.L.2, Bondarenko A.B.2
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Affiliations:
- National Research Center — Institute of Immunology Federal Medical-Biological Agency of Russia
- Scientific and Production Association “Home of Pharmacy”
- Issue: Vol 18, No 2 (2021)
- Pages: 20-31
- Section: Original studies
- URL: https://rusalljournal.ru/raj/article/view/1445
- DOI: https://doi.org/10.36691/RJA1445
Cite item
Abstract
BACKGROUND: Many antagonists of histamine (H1) receptor, in addition to antihistamine action, suppress allergic inflammation by inhibiting the formation and secretion of proinflammatory cytokines. The new antiallergic drug benzhydrylpiperazinyl butylmethylxanthine succinate (theoritin), which has an antihistamine activity comparable to the known second generation H1-antihistamines, surpasses them in the ability to suppress the allergic inflammatory reaction, which allows this drug to have additional anti-inflammatory properties associated with the inhibition of the formation of proinflammatory cytokines.
AIM: This study aimed to determine the effect of theoritin on the induced release of proinflammatory cytokines interleukin (IL)-6, IL-8, and tumor necrosis factor (TNF)-α in cell culture in comparison with the action of the inverse agonist of H1 receptor cetirizine and a known inflammation inhibitor glucocorticosteroid dexamethasone.
MATERIALS AND METHODS: U937 cells differentiated toward macrophage-like cells were used. Cytotoxicity of the substances used was assessed in the methyltetrazolium test at different incubation times (up to 24 h). Cells were stimulated with lipopolysaccharide (LPS). The tested compounds (theoritin and cetirizine) were evaluated at concentrations from 0.001 to 100 μM and dexamethasone at 10 μM was tested when added to cells 1 h before (prophylactic effect) or 1 h after (therapeutic effect) the addition of LPS. The presence of IL-6, IL-8, and TNFα in the supernatants was determined by enzyme immunoassay.
RESULTS: For cetirizine and theoritin, no cytotoxic action was found in the tested concentrations and time points. Dexamethasone inhibited the formation of IL-6 and TNFα to the initial level and IL-8 to 50%–60%. Theoritin led to a significant concentration-dependent decrease in the LPS-induced production of IL-6, IL-8, and TNFα, and at a concentration of 100 μM, the effect of theoritin was comparable with that of dexamethasone at a concentration of 10 μM. The “prophylactic” test scheme for theoritin was more effective in suppressing LPS-induced production of proinflammatory cytokines than the “curative” one. The described effect of theoritin on LPS-induced production of proinflammatory cytokines exceeded that of the reference drug cetirizine.
CONCLUSION: In addition to its antihistaminic action, theoritin, a new antiallergic agent, inhibits LPS-induced production of proinflammatory cytokines, which may be of clinical importance in suppressing allergic inflammation.
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About the authors
Igor S. Gushchin
National Research Center — Institute of Immunology Federal Medical-Biological Agency of Russia
Author for correspondence.
Email: igushchin@yandex.ru
ORCID iD: 0000-0002-4465-6509
SPIN-code: 1905-4758
MD, PhD, professor, corresponding member of Russian Academy of Sciences, head of the Departament of Clinical Immunology and Allergology
Russian Federation, 24, Kashirskoe shosse, Moscow, 115522Kirill L. Kryshen
Scientific and Production Association “Home of Pharmacy”
Email: info@doclinika.ru
ORCID iD: 0000-0003-1451-7716
SPIN-code: 5650-2840
Cand. Sci. (Biol.)
Russian Federation, Leningrad region, Kuzmolovsky villageAndrei B. Bondarenko
Scientific and Production Association “Home of Pharmacy”
Email: info@doclinika.ru
ORCID iD: 0000-0002-8437-1313
SPIN-code: 3376-6819
Russian Federation, Leningrad region, Kuzmolovsky village
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