Oral omega 3 in different proportions of EPA, DHA, and antioxidants as adjuvant in
            treatment of keratoconjunctivitis sicca in dogs

Silva, Danielle Alves; Nai, Gisele Alborghetti; Giuffrida, Rogério; Sgrignoli, Marcos Rógério; Santos, Daniela Rodrigues dos; Donadão, Isabela Vasconcelos; Nascimento, Felipe Franco; Dinallo, Heloíse Rangel; Andrade, Silvia Franco

doi:10.5935/0004-2749.20180081

Cited by 11 publications

(17 citation statements)

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“…Previously, the deficiency of DHA and EPA was found to correlate with the clinical manifestations of DES [21]. Consistently, the daily supplementation of these ω-3 PUFAs was found to reduce or reverse the symptoms of DES in different species including humans [74][75][76]. DHA is a well-recognized precursor of proresolving lipid mediators, controlling epithelial wound healing, inflammatory cell migration and nerve regeneration [21].…”

Section: Discussionmentioning

confidence: 80%

Inflammation in Dry Eye Syndrome: Identification and Targeting of Oxylipin-Mediated Mechanisms

et al. 2020

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Dry eye syndrome (DES) is characterized by decreased tear production and stability, leading to desiccating stress, inflammation and corneal damage. DES treatment may involve targeting the contributing inflammatory pathways mediated by polyunsaturated fatty acids and their derivatives, oxylipins. Here, using an animal model of general anesthesia-induced DES, we addressed these pathways by characterizing inflammatory changes in tear lipidome, in correlation with pathophysiological and biochemical signs of the disease. The decline in tear production was associated with the infiltration of inflammatory cells in the corneal stroma, which manifested one to three days after anesthesia, accompanied by changes in tear antioxidants and cytokines, resulting in persistent damage to the corneal epithelium. The inflammatory response manifested in the tear fluid as a short-term increase in linoleic and alpha-linolenic acid-derived oxylipins, followed by elevation in arachidonic acid and its derivatives, leukotriene B4 (5-lipoxigenase product), 12-hydroxyeicosatetraenoic acid (12-lipoxigeanse product) and prostaglandins, D2, E2 and F2α (cyclooxygenase products) that was observed for up to 7 days. Given these data, DES was treated by a novel ophthalmic formulation containing a dimethyl sulfoxide-based solution of zileuton, an inhibitor of 5-lipoxigenase and arachidonic acid release. The therapy markedly improved the corneal state in DES by attenuating cytokine- and oxylipin-mediated inflammatory responses, without affecting tear production rates. Interestingly, the high efficacy of the proposed therapy resulted from the synergetic action of its components, namely, the general healing activity of dimethyl sulfoxide, suppressing prostaglandins and the more specific effect of zileuton, downregulating leukotriene B4 (inhibition of T-cell recruitment), as well as upregulating docosahexaenoic acid (activation of resolution pathways).

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Section: Discussionmentioning

confidence: 80%

Inflammation in Dry Eye Syndrome: Identification and Targeting of Oxylipin-Mediated Mechanisms

et al. 2020

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“…Twenty studies were performed in canine patients (12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31) and three studies in feline patients (32)(33)(34), with a total of 978 dogs and 68 cats evaluated. In dogs, five types of nonneoplastic diseases were studied: i) allergic dermatitis (13,16,17,(27)(28)(29)(30)(31), ii) osteoarthritis (12,(19)(20)(21)(22)26), iii) periodontal disease (14), iv) keratoconjunctivitis sicca (24) and v) cardiovascular disorders (18,23). According to the eligibility criteria, an additional study was reviewed for assessing a health issue, such as a poor quality haircoat, rather than a particular disease (25).…”

Section: Resultsmentioning

confidence: 99%

“…The methods most often used in the investigator's assessment were: i) scoring systems and ii) scales (12-14, 16, 17, 20-23, 25-29, 34). In addition, patients' status was assessed through i) subjective clinical evaluation (12,33), ii) objective clinical tests and measurements (18,24), iii) medication adjustment needs (21), iv) visual analogue scale (VAS) (17,26,34), v) force plate analysis (19,20), vi) activity monitor (AM) counts (34) and vii) time periods, such as disease-free interval (DFI) (15) and survival time (ST) (15,23). Regarding the owners' evaluation, questionnaires were carried out to obtain information on the severity of clinical signs (13, 17, 19-22, 27, 34), their overall opinion on the treatment response (12,13,30,31) and quality of life (34), as well as their perception of the clinical condition (29), behavior (32) and activity of their pets (32).…”

Section: Resultsmentioning

confidence: 99%

“…Its effect has also been studied in animal species and the therapeutic advantage of topical application of EPA and DHA fatty acids has already been shown through an experimental study conducted in mice (45). Regarding the scope of this review, Silva et al (24) have described a clinical improvement in canine patients diagnosed with KCS when oral supplementation with long-chain omega-3 fatty acids was added to conventional treatment with topical tacrolimus. This clinical result was superior when a higher proportion of EPA than DHA was provided.…”

Section: Non-neoplastic Diseasesmentioning

confidence: 99%

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Therapeutic Effect of EPA/DHA Supplementation in Neoplastic and Non-neoplastic Companion Animal Diseases: A Systematic Review

Magalhães

Lourenço

Gregório

et al. 2021

In Vivo

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Background/Aim: The aim of this study is to identify and describe randomized controlled studies evaluating the therapeutic effect of EPA and DHA supplementation in companion animal diseases. Materials and Methods: A systematic search was conducted in PubMed database and the information collected was summarized and evaluated according to the risk of bias, using the revised Cochrane tool (RoB2). Results: Twenty-three studies were eligible for inclusion: twenty performed in dogs and three in cats. A therapeutic benefit was found in canine allergic dermatitis, haircoat disorder, keratoconjunctivitis sicca, valvular disease, and canine and feline osteoarthritis. Dogs diagnosed with chronic heart failure and lymphoma and cats with allergic dermatitis also seem to benefit from supplementation with omega-3 fatty acids, but studies with improved methodological quality are needed to strengthen this evidence. Conclusion: EPA and DHA supplementation has proven benefits in the adjuvant treatment of various neoplastic and non-neoplastic diseases in dogs and cats.The use of nutraceuticals in the prevention and treatment of canine and feline diseases has been increasing as a result of a greater awareness of their effects by veterinarians. Omega-3 fatty acids are one of the most frequently prescribed products in small animal practices, mainly in the form of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) (1).EPA and DHA are two types of omega-3 polyunsaturated fatty acids (PUFAs) that are derived from alpha-linolenic acid (ALA) through a metabolic pathway that includes chain elongation and desaturation. Since their bioconversion is very limited in dogs and cats, these omega-3 fatty acids need to be supplied to the animal through its diet (2, 3). The main source of EPA and DHA are fish and fish-oil products, such as menhaden, cod liver and salmon oils, even though crustaceans, bivalves, cephalopods and marine algae are also rich sources (4).Supplementation with EPA and DHA has shown benefits in the treatment of several human disorders, such as diabetes, cardiovascular problems, psychiatric and psychological disturbances, rheumatoid arthritis and even cancer (4). Regarding veterinary patients, inflammatory skin disorders, cardiovascular conditions, renal disease and osteoarthritis are the main non-neoplastic diseases where the EPA and DHA seem to have the most impact. Omega-3 fatty acid supplementation has also been used in adjuvant treatment of neoplastic diseases, however, the studies reported in these patients are more scarce (5). It is currently assumed that the benefit of these fatty acids is due to their immunomodulatory and lower-inflammatory effects because of its competitive 1419 This article is freely accessible online.

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“…Furthermore, differences in their influence on transduction pathways, the release of inflammatory cytokines, and the expression of genes involved in lipid metabolism have also been reported [ 40 ]. In the field of ophthalmology, one article compared the effect of two different EPA/DHA formulations (1/4.5 and 1.5/1) as adjuvants to topical tacrolimus in a model of keratoconjunctivitis sicca (dry eye disease) in dogs [ 41 ]. Authors reported better clinical and biochemical outcomes after supplementation with the oral formulation containing a higher proportion of EPA.…”

Section: Discussionmentioning

confidence: 99%

A Higher Proportion of Eicosapentaenoic Acid (EPA) When Combined with Docosahexaenoic Acid (DHA) in Omega-3 Dietary Supplements Provides Higher Antioxidant Effects in Human Retinal Cells

et al. 2020

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Retinal pigment epithelium (RPE) is a key regulator of retinal function and is directly related to the transport, delivery, and metabolism of long-chain n-3 polyunsaturated fatty acids (n3-PUFA), in the retina. Due to their functions and location, RPE cells are constantly exposed to oxidative stress. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have shown to have antioxidant effects by different mechanisms. For this reason, we designed an in vitro study to compare 10 formulations of DHA and EPA supplements from different origins and combined in different proportions, evaluating their effect on cell viability, cell proliferation, reactive oxygen species production, and cell migration using ARPE-19 cells. Furthermore, we assessed their ability to rescue RPE cells from the oxidative conditions seen in diabetic retinopathy. Our results showed that the different formulations of n3-PUFAs have a beneficial effect on cell viability and proliferation and are able to restore oxidative induced RPE damage. We observed that the n3-PUFA provided different results alone or combined in the same supplement. When combined, the best results were obtained in formulations that included a higher proportion of EPA than DHA. Moreover, n3-PUFA in the form of ethyl-esters had a worse performance when compared with triglycerides or phospholipid based formulations.

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Oral omega 3 in different proportions of EPA, DHA, and antioxidants as adjuvant in treatment of keratoconjunctivitis sicca in dogs

Abstract: Oral treatment with ω-3 containing a higher proportion of EPA than DHA increased the effectiveness of topical tacrolimus 0.03% in the treatment of keratoconjunctivitis sicca in dogs.

Cited by 11 publications

References 0 publications

Inflammation in Dry Eye Syndrome: Identification and Targeting of Oxylipin-Mediated Mechanisms

Inflammation in Dry Eye Syndrome: Identification and Targeting of Oxylipin-Mediated Mechanisms

Therapeutic Effect of EPA/DHA Supplementation in Neoplastic and Non-neoplastic Companion Animal Diseases: A Systematic Review

A Higher Proportion of Eicosapentaenoic Acid (EPA) When Combined with Docosahexaenoic Acid (DHA) in Omega-3 Dietary Supplements Provides Higher Antioxidant Effects in Human Retinal Cells

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