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1.
Biomed Khim ; 68(3): 177-189, 2022 Jun.
Article in Russian | MEDLINE | ID: mdl-35717582

ABSTRACT

Cyclooxygenase and lipoxygenase derived lipid metabolites of polyunsaturated fatty acids (PUFAs), as well as their role in the inflammation, have been studied quite thoroughly. However, cytochrome P450 derived lipid mediators, as well as their participation in the regulation of the inflammation, need deeper understanding. In recent years, it has become known that PUFAs are oxidized by cytochrome P450 epoxygenases to epoxy fatty acids, which act as the extremely powerful lipid mediators involved in resolving inflammation. Recent studies have shown that the anti-inflammatory mechanisms of ω-3 PUFAs are also mediated by their conversion to the endocannabinoid epoxides. Thus, it is clear that a number of therapeutically relevant functions of PUFAs are due to their conversion to PUFA epoxides. However, with the participation of cytochrome P450 epoxygenases, not only PUFA epoxides, but also other metabolites are formed. They are further are converted by epoxide hydrolases into pro-inflammatory dihydroxy fatty acids and anti-inflammatory dihydroxyeicosatrienoic acids. The study of the role of PUFA epoxides in the regulation of the inflammation and pharmacological modeling of the activity of epoxide hydrolases are the promising strategies for the treatment of the inflammatory diseases. This review systematizes the current literature data of the fatty acid epoxides, in particular, the endocannabinoid epoxides. Their role in the regulation of inflammation is discussed.


Subject(s)
Epoxy Compounds , Fatty Acids, Omega-3 , Anti-Inflammatory Agents , Cytochrome P-450 CYP2J2 , Cytochrome P-450 Enzyme System/metabolism , Endocannabinoids/metabolism , Epoxide Hydrolases/metabolism , Epoxy Compounds/metabolism , Epoxy Compounds/pharmacology , Fatty Acids , Fatty Acids, Omega-3/metabolism , Fatty Acids, Omega-3/pharmacology , Humans , Inflammation/drug therapy
2.
Biomed Khim ; 62(3): 341-7, 2016 Mar.
Article in Russian | MEDLINE | ID: mdl-27420629

ABSTRACT

We examined composition of plasma non-esterified fatty acids (NFAs), erythrocyte fatty acids, levels of eicosanoids in patients with asthma and chronic obstructive pulmonary disease (COPD) with different type of the inflammatory response. The results of our study show that asthma and COPD in remission are associated with changes in the composition NFAs of plasma, FA of erythrocytes, level eicosanoid despite the difference in the regulation of immunological mechanisms of systemic inflammation. These changes are characterized by excessive production of arachidonic acid (20:4n-6) and cyclooxygenase and lipoxygenase metabolites (thromboxane B2, leukotriene B4) and deficiency of their functional antagonist, eicosapentaenoic acid (20:5n-3). The recognized association between altered fatty acid composition and disorders of the immune mechanisms of regulation of systemic inflammation in COPD and asthma demonstrated the important role of fatty acids and their metabolites in persistence of inflammatory processes in diseases of the respiratory system in the condition of remission.


Subject(s)
Arachidonic Acid/blood , Asthma/blood , Eicosapentaenoic Acid/blood , Pulmonary Disease, Chronic Obstructive/blood , Adult , Case-Control Studies , Female , Humans , Inflammation/blood , Leukotriene B4/blood , Lipoxygenases/blood , Male , Prostaglandin-Endoperoxide Synthases/blood , Thromboxane B2/blood
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