Resolvins
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In the last decades, the development of new technologies applied to lipidomics has revitalized the analysis of lipid profile alterations and the understanding of the underlying molecular mechanisms of lipid metabolism, together with their involvement in the occurrence of human disease. Of particular interest is the study of omega-3 and omega-6 long chain polyunsaturated fatty acids (LC-PUFAs), notably EPA (eicosapentaenoic acid, 20:5n-3), DHA (docosahexaenoic acid, 22:6n-3), and ARA (arachidonic acid, 20:4n-6), and their transformation into bioactive lipid mediators. In this sense, new families of PUFA-derived lipid mediators, including resolvins derived from EPA and DHA, and protectins and maresins derived from DHA, are being increasingly investigated because of their active role in the "return to homeostasis" process and resolution of inflammation. Recent findings reviewed in the present study highlight that the omega-6 fatty acid ARA appears increased, and omega-3 EPA and DHA decreased in most cancer tissues compared to normal ones, and that increments in omega-3 LC-PUFAs consumption and an omega-6/omega-3 ratio of 2-4:1, are associated with a reduced risk of breast, prostate, colon and renal cancers. Along with their lipid-lowering properties, omega-3 LC-PUFAs also exert cardioprotective functions, such as reducing platelet aggregation and inflammation, and controlling the presence of DHA in our body, especially in our liver and brain, which is crucial for optimal brain functionality. Considering that DHA is the principal omega-3 FA in cortical gray matter, the importance of DHA intake and its derived lipid mediators have been recently reported in patients with major depressive and bipolar disorders, Alzheimer disease, Parkinson's disease, and amyotrophic lateral sclerosis. The present study reviews the relationships between major diseases occurring today in the Western world and LC-PUFAs. More specifically this review focuses on the dietary omega-3 LC-PUFAs and the omega-6/omega-3 balance, in a wide range of inflammation disorders, including autoimmune diseases. This review suggests that the current recommendations of consumption and/or supplementation of omega-3 FAs are specific to particular groups of age and physiological status, and still need more fine tuning for overall human health and well being.
- Klíčová slova
- Disease, Health, Inflammation, Lipidomics, Lipids, Long chain polyunsaturated fatty acids, Omega-3, Resolvins,
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
AIMS: Granulation tissue (GT) and specialized pro‑resolving mediators such as lipoxins and resolvins are key elements in the successful resolution of periodontitis. Aspirin‑triggered lipoxins and resolvins are even more powerful than their natural analogues. Their biosynthesis can be accelerated by omega-3 fatty acids. The aim of this study was to evaluate the use of GT enriched by aspirin and omega-3 fatty acids during the surgical treatment of periodontitis in an experimental animal model (rabbit). METHODS: In each of 24 rabbits, two experimental periodontal defects were created. In total, 47 defects were treated with open-flap debridement and one of three procedures: (1) GT extracted and soaked with aspirin and omega-3 fatty acids (ASA+OMEGA3 group); (2) GT soaked with saline (PLACEBO group); or (3) GT left untreated (CONTROL group). Then, the GT was replaced in situ. Primary evaluated criteria were the probing pocket depth (PPD) and the clinical attachment level (CAL). Necropsies were harvested 2, 6, and 12 weeks after surgery. The samples were used for histological and molecular biological assessment. RESULTS: A trend of greater PPD and CAL in the ASA+OMEGA3 group was observed at 6 weeks. However, there was no significant difference between them. During the observation period, tissue levels of FGF-7, IL-1β and TIMP-1 showed a statistically significant decrease (P<0.05). For the other variables, the ASA+OMEGA3 group was comparable with the PLACEBO and CONTROL groups. CONCLUSION: This experiment did not demonstrate the superiority of the proposed approach. However, the enriched granulation tissue did not impair healing outcomes.
- Klíčová slova
- granulation tissue, inflammation mediators, lipoxin, oral surgery, periodontitis,
- MeSH
- Aspirin farmakologie MeSH
- granulační tkáň MeSH
- králíci MeSH
- lipoxiny * MeSH
- omega-3 mastné kyseliny * farmakologie MeSH
- parodontitida * farmakoterapie MeSH
- zvířata MeSH
- Check Tag
- králíci MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- Aspirin MeSH
- lipoxiny * MeSH
- omega-3 mastné kyseliny * MeSH
Cardiovascular disease (CVD) is a global public health issue due to its high morbidity, mortality, and economic impact. The implementation of innovative therapeutic alternatives for CVD is urgently required. Specialized proresolving lipid mediators (SPMs) are bioactive compounds derived from ω-3 and ω-6 fatty acids, integrated into four families: Lipoxins, Resolvins, Protectins, and Maresins. SPMs have generated interest in recent years due to their ability to promote the resolution of inflammation associated with the pathogeneses of numerous illnesses, particularly CVD. Several preclinical studies in animal models have evidenced their ability to decrease the progression of atherosclerosis, intimal hyperplasia, and reperfusion injury via diverse mechanisms. Large-scale clinical trials are required to determine the effects of SPMs in humans. This review integrates the currently available knowledge of the therapeutic impact of SPMs in CVD from preclinical and clinical studies, along with the implicated molecular pathways. In vitro results have been promising, and as such, SPMs could soon represent a new therapeutic alternative for CVD.
- Klíčová slova
- atherosclerosis, inflammation, intimal hyperplasia, reperfusion injury, resolution, specialized proresolving mediators,
- MeSH
- ateroskleróza * metabolismus MeSH
- kardiovaskulární nemoci * farmakoterapie MeSH
- kyseliny dokosahexaenové metabolismus farmakologie terapeutické užití MeSH
- lidé MeSH
- mediátory zánětu metabolismus MeSH
- omega-3 mastné kyseliny * metabolismus farmakologie terapeutické užití MeSH
- zánět metabolismus MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- kyseliny dokosahexaenové MeSH
- mediátory zánětu MeSH
- omega-3 mastné kyseliny * MeSH
Inflammatory lung diseases (ILDs) represent a global public health crisis characterized by escalating prevalence, significant morbidity, and substantial mortality. In response to the complex immunopathogenic mechanisms driving these conditions, novel pharmacological strategies targeting resolution pathways have emerged throughout the discovery of specialized pro-resolving lipid mediator (SPM; resolvins, maresins, and protectins) dysregulation across the ILD spectra, positioning these endogenous molecules as promising therapeutic candidates for modulating maladaptive inflammation and promoting tissue repair. Over the past decade, this paradigm has catalyzed extensive translational research into SPM-based interventions as precision therapeutics for respiratory inflammation. In asthma, they reduce mucus hypersecretion, bronchial hyperreactivity, and airway inflammation, with prenatal SPM exposure potentially lowering offspring disease risk. In COPD, SPMs attenuate amyloid A-driven inflammation, normalizing cytokine/chemokine imbalances and oxidative stress and mitigating COVID-19-associated cytokine storm, enhancing survival. This review synthesizes SPMs' pharmacotherapeutic mechanisms in ILDs and evaluates current preclinical and clinical evidence.
- Klíčová slova
- COPD, PUFAs, inflammation, pulmonary diseases, specialized pro-resolving lipid mediators,
- MeSH
- chronická obstrukční plicní nemoc farmakoterapie metabolismus MeSH
- COVID-19 metabolismus MeSH
- kyseliny dokosahexaenové terapeutické užití metabolismus MeSH
- lidé MeSH
- plicní nemoci * farmakoterapie metabolismus MeSH
- SARS-CoV-2 MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- kyseliny dokosahexaenové MeSH
The fatty acyl structure represents the major lipid building block of practically all lipids and therefore is one of the most fundamental categories of these molecules. Fatty acids (FAs) differ particularly in their chain length, number of double bonds and position of the bonds in the chain. The number of double bonds in the unsaturated molecule of FA distinguishes monounsaturated FAs (MUFAs) and polyunsaturated FAs (PUFAs). In the living cell PUFAs represent the dominant substrates for the formation of biologically active compounds--octadecanoids, eicosanoids and docosanoids--classified as oxylipins or as PUFAnoids. The present review focuses only on the groups of PUFAnoids which biological activities comprise a "positive effect" for the cell. This group of omega-3 PUFAnoids consists of lipoxins, resolvins and protectins. All these biologically active lipids are formed mainly in the LOX-pathway. They are part of the cell mechanisms that contribute to the removal of inflammatory cells and restoration of tissue integrity. A new approach to an optimal anti-inflammatory model shows orientation to the dual COX/LOX-inhibition and the stimulation of the protective eicosanoids and docosanoids formation and its considerable therapeutic potential in managing of molecular mechanisms of chronic inflammatory processes.
- MeSH
- antigeny CD59 metabolismus fyziologie MeSH
- kyseliny dokosahexaenové metabolismus fyziologie MeSH
- lipoxiny metabolismus fyziologie MeSH
- omega-3 mastné kyseliny metabolismus fyziologie MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- antigeny CD59 MeSH
- kyseliny dokosahexaenové MeSH
- lipoxiny MeSH
- omega-3 mastné kyseliny MeSH
Chronic pain (CP) is a severe clinical entity with devastating physical and emotional consequences for patients, which can occur in a myriad of diseases. Often, conventional treatment approaches appear to be insufficient for its management. Moreover, considering the adverse effects of traditional analgesic treatments, specialized pro-resolving lipid mediators (SPMs) have emerged as a promising alternative for CP. These include various bioactive molecules such as resolvins, maresins, and protectins, derived from ω-3 polyunsaturated fatty acids (PUFAs); and lipoxins, produced from ω-6 PUFAs. Indeed, SPMs have been demonstrated to play a central role in the regulation and resolution of the inflammation associated with CP. Furthermore, these molecules can modulate neuroinflammation and thus inhibit central and peripheral sensitizations, as well as long-term potentiation, via immunomodulation and regulation of nociceptor activity and neuronal pathways. In this context, preclinical and clinical studies have evidenced that the use of SPMs is beneficial in CP-related disorders, including rheumatic diseases, migraine, neuropathies, and others. This review integrates current preclinical and clinical knowledge on the role of SPMs as a potential therapeutic tool for the management of patients with CP.
- Klíčová slova
- central nervous system sensitization, chronic pain, eicosanoids, inflammation, long-term potentiation, nociception, omega 3 fatty acids, pain management, polyunsaturated fatty acids, specialized pro-resolving lipid mediators,
- MeSH
- chronická bolest metabolismus terapie MeSH
- kyseliny mastné omega-6 metabolismus MeSH
- lidé MeSH
- management bolesti * MeSH
- mediátory zánětu metabolismus MeSH
- omega-3 mastné kyseliny metabolismus MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- kyseliny mastné omega-6 MeSH
- mediátory zánětu MeSH
- omega-3 mastné kyseliny MeSH
White adipose tissue (WAT) is a complex organ with both metabolic and endocrine functions. Dysregulation of all of these functions of WAT, together with low-grade inflammation of the tissue in obese individuals, contributes to the development of insulin resistance and type 2 diabetes. n-3 polyunsaturated fatty acids (PUFAs) of marine origin play an important role in the resolution of inflammation and exert beneficial metabolic effects. Using experiments in mice and overweight/obese patients with type 2 diabetes, we elucidated the structures of novel members of fatty acid esters of hydroxy fatty acids-lipokines derived from docosahexaenoic acid (DHA) and linoleic acid, which were present in serum and WAT after n-3 PUFA supplementation. These compounds contained DHA esterified to 9- and 13-hydroxyoctadecadienoic acid (HLA) or 14-hydroxydocosahexaenoic acid (HDHA), termed 9-DHAHLA, 13-DHAHLA, and 14-DHAHDHA, and were synthesized by adipocytes at concentrations comparable to those of protectins and resolvins derived from DHA in WAT. 13-DHAHLA exerted anti-inflammatory and proresolving properties while reducing macrophage activation by lipopolysaccharides and enhancing the phagocytosis of zymosan particles. Our results document the existence of novel lipid mediators, which are involved in the beneficial anti-inflammatory effects attributed to n-3 PUFAs, in both mice and humans.
- MeSH
- aktivace makrofágů účinky léků MeSH
- antiflogistika chemie terapeutické užití MeSH
- bílá tuková tkáň účinky léků metabolismus MeSH
- buňky 3T3-L1 MeSH
- diabetes mellitus 2. typu imunologie metabolismus MeSH
- estery chemie terapeutické užití MeSH
- fagocytóza účinky léků MeSH
- inzulinová rezistence fyziologie MeSH
- kultivované buňky MeSH
- kyselina linolová chemie MeSH
- kyseliny dokosahexaenové chemie MeSH
- lidé MeSH
- lipopolysacharidy farmakologie MeSH
- myši inbrední C57BL MeSH
- myši MeSH
- nenasycené mastné kyseliny chemie MeSH
- obezita farmakoterapie imunologie metabolismus MeSH
- tukové buňky účinky léků metabolismus MeSH
- zánět farmakoterapie imunologie metabolismus MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- 14-hydroxydocosahexaenoic acid MeSH Prohlížeč
- antiflogistika MeSH
- estery MeSH
- kyselina linolová MeSH
- kyseliny dokosahexaenové MeSH
- lipopolysacharidy MeSH
- nenasycené mastné kyseliny MeSH
Docosahexaenoic acid (DHA) is an essential fatty acid that is recognized as a beneficial dietary constituent and as a source of the anti-inflammatory specialized proresolving mediators (SPM): resolvins, protectins and maresins. Apart from SPMs, other metabolites of DHA also exert potent biological effects. This article summarizes current knowledge on the metabolic pathways involved in generation of DHA metabolites. Over 70 biologically active metabolites have been described, but are often discussed separately within specific research areas. This review follows DHA metabolism and attempts to integrate the diverse DHA metabolites emphasizing those with identified biological effects. DHA metabolites could be divided into DHA-derived SPMs, DHA epoxides, electrophilic oxo-derivatives (EFOX) of DHA, neuroprostanes, ethanolamines, acylglycerols, docosahexaenoyl amides of amino acids or neurotransmitters, and branched DHA esters of hydroxy fatty acids. These bioactive metabolites have pleiotropic effects that include augmenting energy expenditure, stimulating lipid catabolism, modulating the immune response, helping to resolve inflammation, and promoting wound healing and tissue regeneration. As a result they have been shown to exert many beneficial actions: neuroprotection, anti-hypertension, anti-hyperalgesia, anti-arrhythmia, anti-tumorigenesis etc. Given the chemical structure of DHA, the number and geometry of double bonds, and the panel of enzymes metabolizing DHA, it is also likely that novel bioactive derivatives will be identified in the future.
- Klíčová slova
- DHA, DHEA, FAHFA, N-acyl amides, Omega-3 PUFA, Specialized proresolving mediators,
- MeSH
- kyseliny dokosahexaenové chemie metabolismus farmakologie MeSH
- lidé MeSH
- molekulární struktura MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- kyseliny dokosahexaenové MeSH
Long-chain polyunsaturated fatty acids (LC-PUFA) like arachidonic acid (ARA, 20:4n-6), eicosapentaenoic acid (EPA, 20:5n-3), and docosahexaenoic acid (DHA, 22:6n-3) constitute one-third to half of fish sperm lipids. Fish sperm is rich in phospholipid (PL)-primarily phosphatidylcholine, phosphatidylethanolamine, and sphingomyelin. DHA is generally the most abundant LC-PUFA in each PL class, followed by competition between ARA and EPA. While the total n-6: n-3 PUFA ratio does not correlate significantly with sperm biomechanics, LC-PUFA do. DHA positively influences sperm biomechanics, while ARA and EPA may be negatively associated. Fish sperm maintains lower (≤1) total n-6 PUFA per unit of n-3 PUFA but keep a higher (>1) ARA per unit EPA. A weak dietary influence on sperm EPA and DHA exists but not on ARA. The DHA: EPA ratio in fish sperm is often >1, though values <1 occur. Certain species cannot fortify DHA sufficiently during spermatogenesis, diverging through whole genome duplications. Fish sperm can show ARA: EPA ratios greater or less than 1, due to shifts in prostaglandin pathways in different evolutionary eras. DHA-rich PL bilayers provide unique packing and fusogenic properties, with ARA/EPA-derived eicosanoids guiding sperm rheotaxis/chemotaxis, modulated by DHA-derived resolvins. Docosapentaenoic acid (DPA, 22:5n-3) sometimes substitutes for DHA in fish sperm.
- Klíčová slova
- Aquaculture animal nutrition, Evolutionary adaptations, Fish sperm, Lipidomics, Motility mechanisms, Reproductive fitness,
- MeSH
- biologická evoluce MeSH
- biomechanika MeSH
- dieta veterinární MeSH
- kyseliny dokosahexaenové metabolismus chemie analýza MeSH
- nenasycené mastné kyseliny * metabolismus chemie MeSH
- ryby * metabolismus fyziologie MeSH
- spermie * metabolismus MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- kyseliny dokosahexaenové MeSH
- nenasycené mastné kyseliny * MeSH
BACKGROUND: This is the second of two review parts aiming at describing the major physiological roles of fatty acids, as well as their applications in specific conditions related to human health. RESULTS: The review included the current literature published in Pubmed up to March 2011. In humans, fatty acids are a principle energy substrate and structural components of cell membranes (phospholipids) and second messengers. Fatty acids are also ligands of nuclear receptors affecting gene expression. Longer-chain (LC) polyunsaturated fatty acids (PUFA), including eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and arachidonic acid are precursors of lipid mediators such as eicosanoids (prostaglandins, leukotrienes, thromboxanes), resolvins and neuroprotectins. Lipid mediators produced by EPA and DHA (LC n-3 PUFA; mainly found in oily fish) are considered as inflammation-resolving, and thus, fish oil has been characterised as antiinflammatory. Recommendations for EPA plus DHA intake from oily fish vary between 250-450 mg/day. Dietary reference values for fat vary between nutrition bodies, but mainly agree on a low total and saturated fat intake. The existing literature supports the protective effects of LC n-3 PUFA (as opposed to n-6 PUFA and saturated fat) in maternal and offspring health, cardiovascular health, insulin sensitivity, the metabolic syndrome, cancer, critically ill patients, and immune system disorders. CONCLUSION: Fatty acids are involved in multiple pathways and play a major role in health. Further investigation and a nutrigenomics approach to the effects of these biocompounds on health and disease development are imperative and highlight the importance of environmental modifications on disease outcome.
- MeSH
- dietní tuky aplikace a dávkování MeSH
- lidé MeSH
- mastné kyseliny chemie fyziologie MeSH
- výživová politika MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Názvy látek
- dietní tuky MeSH
- mastné kyseliny MeSH