A prospective, randomized, double blind, placebo-controlled evaluation of the effects of eicosapentaenoic acid and docosahexaenoic acid on the clinical signs and erythrocyte membrane polyunsaturated fatty acid concentrations in dogs with osteoarthritis

Mehler, Stephen J.; May, Lauren R.; King, Crystal; Harris, William S.; Shah, Zubin

doi:10.1016/j.plefa.2016.03.015

Cited by 47 publications

(44 citation statements)

References 37 publications

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“…PUFAs have anti-inflammatory and antioxidative properties (Bento et al, 2011;Mehler et al, 2016;Morin et al, 2015;Nobre et al, 2013;Paterniti et al, 2014;Pineda-Peña et al, 2018;Türkez et al, 2012;Wohlers et al, 2003). In the carrageenan-induced paw edema test, a DHA-rich diet for 15 days reduced inflammation (Nakamura, Hamazaki, Kobayashi, & Yazawa, 1994).…”

Section: Discusionmentioning

confidence: 99%

“…n‐3 (fish oil) and n‐6 (soybean oil) PUFA‐rich diets can also reduce carrageenan‐induced paw edema in rats indicating anti‐inflammatory effects (Nobre et al, ; Wohlers, Nascimento, Xavier, Ribeiro, & Silveira, ) while DHA reduced spinal cord inflammation in rat (Paterniti et al, ). Daily supplementation diet with eicosapentaenoic acid and DHA reduced clinical signs associated with osteoarthritis in dogs (Mehler, May, King, Harris, & Shah, ) and in humans; fish oil supplement usage in patients with rheumatoid arthritis were more likely to reduce use of nonsteroidal anti‐inflammatory drugs (NSAIDs) and to be in remission than patients who did not use fish oil (Cleland, Caughey, James, & Proudman, ). A meta‐analysis of n‐3 fatty acids and pain indicated that fish oil reduces patient‐assessed joint pain and use of NSAIDs in patients with rheumatoid arthritis (Goldberg & Katz, ).…”

Section: Introductionmentioning

confidence: 99%

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Synergistic interaction between docosahexaenoic acid and diclofenac on inflammation, nociception, and gastric security models in rats

Miranda-Lara

Ortiz

Rodríguez-Ramos

et al. 2018

Drug Development Research

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Preclinical Research & Development The addition of polyunsaturated fatty acids to nonsteroidal anti-inflammatory drugs can increase their antinociceptive activity and produce a gastroprotective effect. The aim of the present study was to examine the effects of the interaction between docosahexaenoic acid (DHA) and diclofenac on inflammation (fixed ratios 1:1, 1:3, and 3:1), nociception (fixed ratio 1:3), and gastric injury in rats. DHA, diclofenac, or combinations of DHA and diclofenac produced anti-inflammatory and antinociceptive effects in rat. The administration of diclofenac produced significant gastric damage, but this effect was not observed with either DHA or the DHA-diclofenac combinations. Effective dose (ED ) values were estimated for each individual drug and analyzed isobolographically. The anti-inflammatory experimental ED values were 6.97 mg/kg (1:1 fixed ratio), 1.1 mg/kg (1:3 fixed ratio), and 11.34 mg/kg (3:1 fixed ratio). These values were significantly lower (p < .05) than the theoretical ED values: 67.94 mg/kg (1:1), 35.37 mg/kg (1:3), and 100.51 mg/kg (3:1). The antinociceptive experimental value was 1.25 mg/kg (1:3 fixed ratio). This value was lower (p < .05) than the theoretical ED , which was predicted to be 15.92 mg/kg. These data indicate that the DHA-diclofenac combinations interact at the systemic level, produce minor gastric damage, and potentially have therapeutic advantages for the clinical treatment of inflammatory pain.

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Section: Discusionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Synergistic interaction between docosahexaenoic acid and diclofenac on inflammation, nociception, and gastric security models in rats

Miranda-Lara

Ortiz

Rodríguez-Ramos

et al. 2018

Drug Development Research

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“…Academic and private practice veterinary medicine can provide valuable biomedical research data, as referral centres are often equipped with MRI and CT scanners, arthroscopes and state-of-theart pathology and molecular diagnostic capabilities. Academic veterinary centres also pilot advances in the use of anti-inflammatory and pain-modulating OA drug therapies 10,14,15 . In this Review, we summarize research relating to common forms of spontaneous dog OA, focusing on the presentation and genetics of analogous diseases of the hip and knee, within a framework of human OA phenotypes.…”

mentioning

confidence: 99%

Spontaneous dog osteoarthritis — a One Medicine vision

et al. 2019

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| Osteoarthritis (OA) is a global disease that, despite extensive research, has limited treatment options. Pet dogs share both an environment and lifestyle attributes with their owners, and a growing awareness is developing in the public and among researchers that One Medicine, the mutual co-study of animals and humans, could be beneficial for both humans and dogs. To that end, this Review highlights research opportunities afforded by studying dogs with spontaneous OA , with a view to sharing this active area of veterinary research with new audiences. Similarities and differences between dog and human OA are examined, and the proposition is made that suitably aligned studies of spontaneous OA in dogs and humans, in particular hip and knee OA , could highlight new avenues of discovery. Developing cross-species collaborations will provide a wealth of research material and knowledge that is relevant to human OA and that cannot currently be obtained from rodent models or experimentally induced dog models of OA. Ultimately , this Review aims to raise awareness of spontaneous dog OA and to stimulate discussion regarding its exploration under the One Medicine initiative to improve the health and well-being of both species.

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“…It is known that chondrocytes have only limited access to nutrients due to the avascular, dense and negatively charged matrix (Villalvilla, Gómez, Largo, & Herrero‐Beaumont, ). However, feeding studies provide evidence that diets rich in n‐3 fatty acids alter the fatty acid composition in canine serum (Barrouin‐Melo et al., ; Hall, Picton, Skinner, Jewell, & Wander, ; Mehler et al., ) and that fatty acids are generally transported to the joints bound to albumin or lipoproteins (Arkill & Winlove, ). To mimic the process of fatty acid transport, we included 5% of FCS in the culture medium.…”

Section: Discussionmentioning

confidence: 99%

“…Several feeding studies (Fritsch et al., ; Mehler, May, King, Harris, & Shah, ; Moreau et al., ; Roush et al., ) have suggested that dietary supplementation with marine n‐3 fatty acids is beneficial in the treatment of canine OA. Two classes of essential polyunsaturated fatty acids (PUFA) are important as part of a healthy dog diet: the n‐6 fatty acids, for example, arachidonic acid (AA), which are present in meat and vegetable oils, and the n‐3 fatty acids, for example, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), which both are found predominantly in marine feed.…”

Section: Introductionmentioning

confidence: 99%

Polyunsaturated fatty acids influence inflammatory markers in a cellular model for canine osteoarthritis

Adler

Schoeniger

Fuhrmann

2017

Animal Physiology Nutrition

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Although it is well recognized that dietary supplementation with fish oil improves clinical symptoms in dogs suffering from osteoarthritis, the molecular basis for the dietary benefit is not yet completely resolved in dogs. This study was designed to further clarify how polyunsaturated fatty acids (PUFA) affect key factors of cartilage degeneration in a canine cell culture system mimicking osteoarthritis. Canine chondrocytes were incubated either without or with 10 μm of eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), arachidonic acid (AA) or 3.6 μm ibuprofen (Ibu) as positive control for 6 days. After the supplementation, cells were stimulated with 10 ng/ml interleukin-1β (IL-1β) for another 48 hr to induce osteoarthritic changes, or left unstimulated. We analysed fatty acid uptake via gas-liquid chromatography, nitric oxide (NO) production via Griess assay, prostaglandin E (PGE) production via ELISA and relative gene expression of several cartilage matrix proteinases, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 via RT-qPCR. After supplementation, the chondrocytes rapidly incorporated the PUFA into their fatty acid pools. The stimulation with IL-1β caused a marked increase of most of the inflammatory markers measured. N-3 PUFA EPA reduced IL-induced gene expression of iNOS and corresponding production of NO. N-6 PUFA AA also decreased iNOS and NO, but furthermore lowered gene expression of matrix metalloproteinase-3. On the other hand, AA upregulated the aggrecanase ADAMTS-5 and augmented the release of PGE. The effect of n-3 PUFA DHA turned out to be negligible. Our results reveal molecular mechanisms by which PUFA affect degenerative joint disease in dogs. Of particular importance is that not only EPA but also AA decreased several inflammatory markers in our model. Thus, we conclude that an appropriate balance of both n-3 and n-6 fatty acids deserves more attention in dietary interventions.

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A prospective, randomized, double blind, placebo-controlled evaluation of the effects of eicosapentaenoic acid and docosahexaenoic acid on the clinical signs and erythrocyte membrane polyunsaturated fatty acid concentrations in dogs with osteoarthritis

Abstract: This study demonstrated that the daily supplementation of a dogs diet with EPA and DHA shifts the blood fatty acid concentrations correlating to relief of clinical signs associated with OA in dogs.

Cited by 47 publications

References 37 publications

Synergistic interaction between docosahexaenoic acid and diclofenac on inflammation, nociception, and gastric security models in rats

Synergistic interaction between docosahexaenoic acid and diclofenac on inflammation, nociception, and gastric security models in rats

Spontaneous dog osteoarthritis — a One Medicine vision

Polyunsaturated fatty acids influence inflammatory markers in a cellular model for canine osteoarthritis

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