Unknown properties of known drugs: influence of montelukast on the lipid peroxidation processes and structuraldynamic specifics of erythrocyte membranes under adjuvant arthritis

Abstract

Search for new pharmacological properties in known drugs is one of the most relevant tasks of
pharmacology. Montelukast as selective blocker of leukotriene receptors, prevents interactions of
proinflammatory cis leukotrienes (LTC4, LTD4, LTE4) with these receptors, which ensures its effectiveness against bronchial asthma and allergic rhinitis. An ability of montelukast to decrease
secretion of IL-6, IL-8, ММР-3 and ММР-13 in fibroblast-like synoviocytes, induced by IL-1B, allows the
possibility of its use for treatment of rheumatoid arthritis. This is why studies of efficiency of montelukast
during prolonged use for rheumatic diseases may help to establish unknown properties of this drug, and
understand one of the possible mechanisms of realization of anti-inflammatory action of drug in
experimental rheumatoid arthritis. This can contribute to identification of targets for its action and
outline the paths for the search of new compounds, capable of influencing different links of pathogenesis
of inflammatory processes, which gives basis for relevance of research.
The aim of the study – to research an influence of montelukast on processes of lipids peroxidation
and structure-dynamic specifics of erythrocyte membranes in experimental rheumatoid arthritis.
The experiments were conducted on four groups of non-linear white rats of both sexes: 1 – intact
rats; 2 – rats without pathology, which received montelukast; 3 – rats under experimental rheumatoid
arthritis (modeling by subcutaneous injection of Freund's adjuvant); 4 – rats with adjuvant arthritis and
montelukast treatment (intragastric administration once for 14, 28 and 59 days at a dose 1,5 mg/kg).
Lipids peroxidation processes were evaluated by TBA content, catalase activity and reduced glutathione
level; structure-dynamic specifics of erythrocyte membranes – by fluorescent probing with pyrene.
The results obtained indicate moderate prooxidant activity of montelukast in prolonged use on
animals without pathology. On the background of adjuvant arthritis, montelukast showed antioxidant
action, decreasing lipid peroxidation and activating the system of antioxidant protection. Under adjuvant
arthritis montelukast decreased microviscosity oh hydrophobic links of phospholipid bilayer of
erythrocyte membranes, but didn’t cause significant structural changes in erythrocyte membranes in
zones of pyrene probe localization in condition of adjuvant arthritis.
An activity of montelukast in influencing the lipids peroxidation processes determines the possibility
of its use in clinical practice after confirmation of its effectiveness in patients with general inflammatory
processes.
Probably, the mechanism of anti-inflammatory action of montelukast in adjuvant arthritis is partially
mediated by correction of lipids peroxidation processes.
The results of the research regarding antioxidant action of montelukast as antileukotriene drug on
adjuvant arthritis allow to predict prospect of searching for new drugs for therapy of autoimmune
general processes, mechanisms of which are mediated by influence on cisleukotriene receptors.