Implications for eicosapentaenoic acid- and docosahexaenoic acid-derived resolvins as therapeutics for arthritis

Souza, Patricia R.; Norling, Lucy V.

doi:10.1016/j.ejphar.2015.05.072

Cited by 30 publications

(21 citation statements)

References 95 publications

(105 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The long-chain omega-3 fatty acid DHA (22:6n-3) is best known for its cardioprotective properties, due in part to its incorporation into cell membranes, resulting in a direct effect on calcium channels and their role in eicosanoid metabolism [ 26 , 27 , 28 ]. The mechanism by which AA / EPA and DHA are immunomodulatory seems to be due to derivatives of these PUFAs [ 29 ], including bioactive lipid mediators called resolvins, protectins, and marescins, which have potent anti-inflammatory and immunoregulatory action in vitro and in vivo [ 30 , 31 ]. While the sunitinib-induced decreases in these potent anti-inflammatory mediators cannot be directly linked to the observed cardiotoxicity, these findings do suggest a novel link between sunitinib-induced cardiotoxicity and alterations in inflammation through its effects on DHA, arachidonic acid, and O-phosphocolamine (aka phosphoethanolamine).…”

Section: Discussionmentioning

confidence: 99%

Non-Targeted Metabolomics Analysis of the Effects of Tyrosine Kinase Inhibitors Sunitinib and Erlotinib on Heart, Muscle, Liver and Serum Metabolism In Vivo

et al. 2017

View full text Add to dashboard Cite

Background: More than 90 tyrosine kinases have been implicated in the pathogenesis of malignant transformation and tumor angiogenesis. Tyrosine kinase inhibitors (TKIs) have emerged as effective therapies in treating cancer by exploiting this kinase dependency. The TKI erlotinib targets the epidermal growth factor receptor (EGFR), whereas sunitinib targets primarily vascular endothelial growth factor receptor (VEGFR) and platelet-derived growth factor receptor (PDGFR).TKIs that impact the function of non-malignant cells and have on- and off-target toxicities, including cardiotoxicities. Cardiotoxicity is very rare in patients treated with erlotinib, but considerably more common after sunitinib treatment. We hypothesized that the deleterious effects of TKIs on the heart were related to their impact on cardiac metabolism. Methods: Female FVB/N mice (10/group) were treated with therapeutic doses of sunitinib (40 mg/kg), erlotinib (50 mg/kg), or vehicle daily for two weeks. Echocardiographic assessment of the heart in vivo was performed at baseline and on Day 14. Heart, skeletal muscle, liver and serum were flash frozen and prepped for non-targeted GC-MS metabolomics analysis. Results: Compared to vehicle-treated controls, sunitinib-treated mice had significant decreases in systolic function, whereas erlotinib-treated mice did not. Non-targeted metabolomics analysis of heart identified significant decreases in docosahexaenoic acid (DHA), arachidonic acid (AA)/ eicosapentaenoic acid (EPA), O-phosphocolamine, and 6-hydroxynicotinic acid after sunitinib treatment. DHA was significantly decreased in skeletal muscle (quadriceps femoris), while elevated cholesterol was identified in liver and elevated ethanolamine identified in serum. In contrast, erlotinib affected only one metabolite (spermidine significantly increased). Conclusions: Mice treated with sunitinib exhibited systolic dysfunction within two weeks, with significantly lower heart and skeletal muscle levels of long chain omega-3 fatty acids docosahexaenoic acid (DHA), arachidonic acid (AA)/eicosapentaenoic acid (EPA) and increased serum O-phosphocholine phospholipid. This is the first link between sunitinib-induced cardiotoxicity and depletion of the polyunsaturated fatty acids (PUFAs) and inflammatory mediators DHA and AA/EPA in the heart. These compounds have important roles in maintaining mitochondrial function, and their loss may contribute to cardiac dysfunction.

show abstract

Section: Discussionmentioning

confidence: 99%

Non-Targeted Metabolomics Analysis of the Effects of Tyrosine Kinase Inhibitors Sunitinib and Erlotinib on Heart, Muscle, Liver and Serum Metabolism In Vivo

et al. 2017

View full text Add to dashboard Cite

show abstract

“…It is now well established that acute inflammation is accompanied by an active program of resolution that begins in the first few hours after the onset of inflammation and involves the synthesis of specialized pro‐resolving mediators (SPMs) derived from dietary n‐3 polyunsaturated fatty acids including resolvins, protectins, and maresins (Serhan et al, ; Serhan, ). While there is considerable interest in the clinical development of pharmacological agents and nutritional approaches that can promote the resolution of inflammation via these pathways and mediators (Norling et al, ; Cholkar et al, ; Souza and Norling, ), it is also important to understand naturally occurring mechanisms that might enhance the resolution of inflammation without the use of drugs, one of which being physical activity, particularly stretching.…”

mentioning

confidence: 99%

Stretching Impacts Inflammation Resolution in Connective Tissue

et al. 2015

View full text Add to dashboard Cite

Acute inflammation is accompanied from its outset by the release of specialized pro-resolving mediators (SPMs), including resolvins, that orchestrate the resolution of local inflammation. We showed earlier that, in rats with subcutaneous inflammation of the back induced by carrageenan, stretching for 10 minutes twice daily reduced inflammation and improved pain, two weeks after carrageenan injection. In this study, we hypothesized that stretching of connective tissue activates local pro-resolving mechanisms within the tissue in the acute phase of inflammation. In rats injected with carrageenan and randomized to stretch vs. no stretch for 48 hours, stretching reduced inflammatory lesion thickness and neutrophil count, and increased resolvin (RvD1) concentrations within lesions. Furthermore, subcutaneous resolvin injection mimicked the effect of stretching. In ex vivo experiments, stretching of connective tissue reduced the migration of neutrophils and increased tissue RvD1 concentration. These results demonstrate a direct mechanical impact of stretching on inflammation-regulation mechanisms within connective tissue.

show abstract

“…DHA can generate a new type of bioactive lipid mediator through biological derivatization. These endogenous mediators can act on specific G protein-coupled receptors (GPCRs) to inhibit inflammation [ 32 ]. The content of DHA significantly increased in the MG, indicating that the body showed a stress response to the inflammation caused by RA.…”

Section: Resultsmentioning

confidence: 99%

K Nearest Neighbor Algorithm Coupled with Metabonomics to Study the Therapeutic Mechanism of Sendeng‐4 in Adjuvant‐Induced Rheumatoid Arthritis Rat

Wang

Jiang

et al. 2018

Evidence-Based Complementary and Alternative Medicine

View full text Add to dashboard Cite

As a traditional Mongolian medicine, Sendeng-4 (SD) has been widely used to treat rheumatoid arthritis (RA) in Inner Mongolia and exhibits a good curative effect. Unfortunately, due to geographical factors, it is difficult to popularize this drug throughout the whole country, and the mechanism of action of SD has been unclear. In this study, a serum metabolite profile analysis was performed to identify potential biomarkers associated with adjuvant-induced RA and investigate the mechanism of action of SD. Ultraperformance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) was performed for the metabonomics analysis. K nearest neighbor (KNN) models were established in both positive and negative spectra for classifying data from the control, model, and SD administration groups. Accuracy rate for classification was 95.8% in positive ion mode and 91.7% in negative ion mode. Orthogonal partial least squares discriminant analysis (OPLS-DA) enabled the identification of 12 metabolites as potential biomarkers of adjuvant-induced RA. After treatment with SD, the levels of uridine triphosphate, calcitroic acid, dynorphin B (6-9), and docosahexaenoic acid were restored to normal, indicating that SD likely ameliorated RA by regulating the levels of these biomarkers. This study identified early biomarkers of RA and elucidated the underlying mechanism of action of SD, which is worth further investigation for development as a clinical therapy.

show abstract

Implications for eicosapentaenoic acid- and docosahexaenoic acid-derived resolvins as therapeutics for arthritis

Cited by 30 publications

References 95 publications

Non-Targeted Metabolomics Analysis of the Effects of Tyrosine Kinase Inhibitors Sunitinib and Erlotinib on Heart, Muscle, Liver and Serum Metabolism In Vivo

Non-Targeted Metabolomics Analysis of the Effects of Tyrosine Kinase Inhibitors Sunitinib and Erlotinib on Heart, Muscle, Liver and Serum Metabolism In Vivo

Stretching Impacts Inflammation Resolution in Connective Tissue

K Nearest Neighbor Algorithm Coupled with Metabonomics to Study the Therapeutic Mechanism of Sendeng‐4 in Adjuvant‐Induced Rheumatoid Arthritis Rat

Contact Info

Product

Resources

About